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1.
Nano Lett ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941514

RESUMO

Organic dyes with simultaneously boosted near-infrared-II (NIR-II) fluorescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) in the aggregate state are still elusive due to the unclear structure-function relationship. Herein, electron-withdrawing substituents are introduced at the 5-indolyl positions of BODIPY dyes to form tight J-aggregates for enhanced NIR-II fluorescence and type I PDT/PTT. The introduction of an electron-rich julolidine group at the meso position and an electron-withdrawing substituent (-F) at the indolyl moiety can enhance intermolecular charge transfer and the hydrogen bonding effect, contributing to the efficient generation of superoxide radicals in the aggregate state. The nanoparticles of BDP-F exhibit NIR-II fluorescence at 1000 nm, good superoxide radical generation ability, and a high photothermal conversion efficiency (50.9%), which enabled NIR-II fluorescence-guided vasculature/tumor imaging and additive PDT/PTT. This work provides a strategy for constructing phototheranostic agents with enhanced NIR-II fluorescence and type I PDT/PTT for broad biomedical applications.

2.
Pancreatology ; 24(1): 130-136, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38016861

RESUMO

BACKGROUND: Laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) is a surgical method used to treat benign and low-grade malignant pancreatic head tumors. This study aimed to determine the protective effect of common bile duct in LDPPHR using indocyanine green (ICG) fluorescence imaging. METHODS: A retrospective analysis of 30 patients treated with LDPPHR at the Second Affiliated Hospital of Nanchang University between January 2015 and November 2022 was performed. Patients were divided into two groups based on ICG use: ICG and non-ICG. RESULTS: Thirty patients received LDPPHR, 11 males and 19 females, and the age was 50.50 (M (IQR)) years (range: 19-76 years). LDPPHR was successfully performed in 27 (90 %) patients, LPD was performed in 1 (3 %) patient, and laparotomy conversion was performed in 2 (7 %) patients. One patient (3 %) died 21 days after surgery. The incidence of intraoperative bile duct injury in the ICG group was lower than that in the non-ICG group (10 % vs 60 %, P = 0.009), and the operation time in the ICG group was shorter than that in the non-ICG group (311.9 ± 14.97 vs 338.05 ± 18.75 min, P < 0.05). Postoperative pancreatic fistula occurred in 16 patients (53 %), including 10 with biochemical leakage (62.5 %), four with grade B (25 %), and two with grade C (12.5 %). Postoperative bile leakage occurred in four patients (13 %). CONCLUSIONS: The ICG fluorescence imaging technology in LDPPHR helps protect the integrity of the common bile duct and reduce the occurrence of intraoperative bile duct injury, postoperative bile leakage, and bile duct stenosis.


Assuntos
Doenças dos Ductos Biliares , Laparoscopia , Masculino , Feminino , Humanos , Verde de Indocianina , Estudos Retrospectivos , Laparoscopia/métodos , Doenças dos Ductos Biliares/etiologia , Imagem Óptica/efeitos adversos , Imagem Óptica/métodos , Duodeno/diagnóstico por imagem , Duodeno/cirurgia
3.
Surg Endosc ; 37(12): 9116-9124, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37803187

RESUMO

BACKGROUND: This study aimed to investigate the safety and efficacy of laparoscopic anatomical left hemihepatectomy guided by the middle hepatic vein (MHV) for the treatment of patients with hepatolithiasis who had a history of upper abdominal surgery. METHODS: Retrospective data analysis was performed on patients who underwent laparoscopic left hepatectomy for hepatolithiasis and with previous upper abdominal surgery at the Second Affiliated Hospital of Nanchang University from January 2018 to April 2022. According to the different surgical approaches, patients were divided into laparoscopic anatomical left hepatectomy guided by the MHV group (MHV-AH group) and laparoscopic traditional anatomical left hepatectomy not guided by the MHV group (non-MHV-AH group). RESULTS: This study included 81 patients, with 37 and 44 patients in the MHV-AH and non-MHV-AH groups, respectively. There was no significant difference in the basic information between the two groups. Five cases were converted to laparotomy, and the remaining were successfully completed under laparoscopy. Compared to the non-MHV-AH group, the MHV-AH group had a slightly longer operation time (319.30 min vs 273.93 min, P = 0.032), lower bile leakage rate (5.4% vs 20.5%, P = 0.047), stone residual rate (2.7% vs 20.5%, P = 0.015), stone recurrence rate (5.4% vs 22.7%, P = 0.028), and cholangitis recurrence rate (2.7% vs 22.7%, P = 0.008).There were no significant differences in the results of other observation indices between the groups. CONCLUSIONS: Laparoscopic anatomical left hepatectomy guided by the MHV is safe and effective in the treatment of left hepatolithiasis with a history of upper abdominal surgery. It does not increase intraoperative bleeding and reduces the risk of postoperative bile leakage, residual stones, stone recurrence, and cholangitis recurrence.


Assuntos
Cálculos , Colangite , Laparoscopia , Litíase , Hepatopatias , Humanos , Hepatectomia/métodos , Hepatopatias/cirurgia , Litíase/cirurgia , Estudos Retrospectivos , Veias Hepáticas , Resultado do Tratamento , Cálculos/cirurgia , Laparoscopia/métodos , Colangite/etiologia
4.
J Am Chem Soc ; 145(44): 24302-24314, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37853662

RESUMO

Lipid nanoparticles (LNPs) represent the most clinically advanced nonviral mRNA delivery vehicles; however, the full potential of the LNP platform is greatly hampered by inadequate endosomal escape capability. Herein, we rationally introduce a disulfide bond-bridged ester linker to modularly synthesize a library of 96 linker-degradable ionizable lipids (LDILs) for improved mRNA delivery in vivo. The top-performing LDILs are composed of one 4A3 amino headgroup, four disulfide bond-bridged linkers, and four 10-carbon tail chains, whose unique GSH-responsive cone-shaped architectures endow optimized 4A3-SCC-10 and 4A3-SCC-PH lipids with superior endosomal escape and rapid mRNA release abilities, outperforming their parent lipids 4A3-SC-10/PH without a disulfide bond and control lipids 4A3-SSC-10/PH with a disulfide bond in the tail. Notably, compared to DLin-MC3-DMA via systematic administration, 4A3-SCC-10- and 4A3-SCC-PH-formulated LNPs significantly improved mRNA delivery in livers by 87-fold and 176-fold, respectively. Moreover, 4A3-SCC-PH LNPs enabled the highly efficient gene editing of 99% hepatocytes at a low Cre mRNA dose in tdTomato mice following intravenous administration. Meanwhile, 4A3-SCC-PH LNPs were able to selectively deliver firefly luciferase mRNA and facilitate luciferase expression in tumor cells after intraperitoneal injection, further improving cancer metastasis delineation and surgery via bioluminescence imaging. We envision that the chemistry adopted here can be further extended to develop new biodegradable ionizable lipids for broad applications such as gene editing and cancer immunotherapy.


Assuntos
Nanopartículas , Neoplasias , Camundongos , Animais , RNA Mensageiro/metabolismo , Lipídeos/química , Sistemas de Liberação de Medicamentos , Fígado/metabolismo , Nanopartículas/química , Dissulfetos/metabolismo , RNA Interferente Pequeno/genética , Neoplasias/metabolismo
5.
Anal Chem ; 95(32): 12054-12061, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37528071

RESUMO

Noninvasive visualization of liver polarity by using fluorescence imaging technology is helpful to better understand drug-induced liver injury (DILI). However, cell membrane-targeted polarity-sensitive near-infrared (NIR) fluorescent probes are still scarce. Herein, we report a non-solvatochromic cell membrane-targeted NIR small molecular probe (N-BPM-C10) for monitoring the polarity changes on cell membranes in living cells and in vivo. N-BPM-C10 exhibits polarity-dependent fluorescence around 655 nm without an obvious solvatochromic effect, which endows it with good capability for the in vivo imaging study. Moreover, it can rapidly and selectively light up the cell membranes as well as distinguish tumor cells from normal cells due to its excellent polarity-sensitive ability. More importantly, N-BPM-C10 has been successfully applied to visualize liver polarity changes in vivo, revealing the reduction of liver polarity in DILI mice. We believe that N-BPM-C10 provides a new way for the diagnosis of DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Corantes Fluorescentes , Camundongos , Animais , Corantes Fluorescentes/metabolismo , Maleimidas , Membrana Celular/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Imagem Óptica
6.
Angew Chem Int Ed Engl ; 62(38): e202309768, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37559354

RESUMO

Conventional cyanine dyes with a symmetric structure are "always-on", which can easily accumulate in the liver and display high liver background fluorescence, inevitably interfering the accurate diagnosis and therapy in extrahepatic diseases. We herein report a platform of NIR-II non-symmetric cyanine (NSCyanine) dyes by harnessing a non-symmetric strategy, which are extremely sensitive to pH/viscosity and can be activated via a "dual-key-and-lock" strategy. These NSCyanine dyes with a low pKa (<4.0) only show weak fluorescence at lysosome pH (key1), however, the fluorescence can be completely switched on and significantly enhanced by intracellular viscosity (key2) in disease tissues, exhibiting high target-to-liver ratios up to 19.5/1. Notably, high-contrast phototheranostics in extrahepatic diseases are achieved, including intestinal metastasis-imaging, acute gastritis-imaging, bacteria infected wound healing, and tumor ablation via targeted combined photothermal therapy and chemotherapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Diagnóstico por Imagem , Corantes , Fluorescência , Fototerapia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
7.
Medicine (Baltimore) ; 102(26): e34163, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37390255

RESUMO

At present, the extent of lymph node dissection (LND) for radical gallbladder cancer (GBC) is still controversial, and there is no evidence that LND improves prognosis, however, the latest guidelines for GBC recommend that removal of more than 6 lymph nodes facilitates staging of regional lymph nodes. The aim of this study is to investigate the effect of different LND methods on the number of lymph nodes detected and assess the prognostic factors during radical resection of GBC. This study retrospectively analyzed 133 patients (46 men and 87 women; average age: 64.01, range: 40-83 years) who underwent radical resection of GBC in a single center between July 2017 and July 2022, of which 41 underwent fusion lymph node dissection (FLND) and 92 underwent standard lymph node dissection (SLND). Baseline data, surgical results, number of LNDs, and follow-up data were analyzed. Each patient was followed up every 3 months. The total number of lymph nodes detected after the operation was 12.00 ± 6.95 versus 6.10 ± 4.71 (P < .05). The number of positive lymph nodes detected was (mean) 1.85 versus 0.78 and (percentage) 15.45% versus 12.83% (P < .05). Postoperative complications (8 vs 23, P > .05). The progression-free survival was 13 versus 8 months, the median survival time was 17 versus 9 months (P < .05). This study concluded that FLND can increase the detection rate of total lymph nodes and positive lymph nodes after surgery, which can prolong the survival time of patients.


Assuntos
Carcinoma in Situ , Neoplasias da Vesícula Biliar , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Vesícula Biliar/cirurgia , Estudos Retrospectivos , Excisão de Linfonodo , Linfonodos/cirurgia , Prognóstico
8.
Front Immunol ; 14: 1144371, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37020545

RESUMO

Gallbladder cancer (GBC) and cholangiocarcinoma are common cancers of the biliary system and are associated with a poor prognosis. Surgery and chemotherapy provide limited benefit to patients with advanced biliary tract carcinoma. Novel immunotherapies and molecularly targeted therapies are more effective options; however, few patients benefit and drug resistance is a concern. Here, we report five cases of advanced GBC with either high programmed death-ligand 1 (PD-L1) expression or a high tumor mutation burden (TMB-H). The patients were treated with a combination therapy of tislelizumab and S-1. The tumors were effectively controlled in most patients. One patient developed immune-related pneumonia (irP) during treatment, which resolved after hormone therapy, and the patient underwent surgery. Tislelizumab and S-1 were administered again after surgery; however, recurrent irP required discontinuation, and the tumor progressed after drug withdrawal. These cases demonstrate that combined therapy of anti-programmed cell death protein-1 (PD-1) antibodies and S-1 is a safe and effective regimen with few side effects for GBC patients, especially for sensitive populations (patients with TMB-H, microsatellite instability, deficient mismatch repair, or high expression of PD-L1). To our knowledge, this is the first time that tislelizumab in combination with S-1 has been used to treat patients with advanced GBC.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/tratamento farmacológico , Antígeno B7-H1 , Anticorpos Monoclonais Humanizados/uso terapêutico , Colangiocarcinoma/tratamento farmacológico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos
9.
J Gastrointest Surg ; 27(3): 555-564, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36652180

RESUMO

BACKGROUND: Laparoscopic transcystic common bile duct exploration (LTCBDE) is used to treat cholecystolithiasis and choledocholithiasis. This study aimed to investigate the safety, effectiveness and generalisability of LTCBDE in patients with cholecystolithiasis and choledocholithiasis based on our LTCBDE experience within 8 years. METHODS: Four hundred patients with cholecystolithiasis and choledocholithiasis (including 62 of cholecystolithiasis and choledocholithiasis with common bile duct no-dilatation) treated with LTCBDE at a single centre from January 2014 to February 2022 were retrospectively evaluated. They were divided into the first 200 and last 200 LTCBDE cases. The disease characteristics, cystic duct incision methods, surgical outcomes and follow-up data were analysed retrospectively. Each patient was followed up for > 3 months. RESULTS: Four hundred patients underwent LTCBDE, including 188 males and 212 females aged from 15 to 91 years (average age: 56 years). LTCBDE was successful in 377 (94.3%) patients, while treatment was converted to laparoscopic choledocholithotomy with T-tube drainage in 23 (5.8%), owing to intraoperative choledochoscope insertion failure. The CBD diameter (10.89 ± 1.76 vs 9.97 ± 2.39, P < 0.05), cystic duct diameter (4.62 ± 1.03 vs 5.03 ± 1.29, P < 0.05), and operation time (164.60 ± 24.30 vs 135.34 ± 30.00, P < 0.05). Residual stones were found in six (1.5%) patients and removed during the second operation; post-operative bile leakage was found in one (0.3%) patient, who was discharged safely after the second operation. CONCLUSIONS: Phase I LTCBDE is safe and effective in treating cholecystolithiasis and choledocholithiasis. With continuous technological advances, LTCBDE has been effectively promoted and applied.


Assuntos
Colecistectomia Laparoscópica , Colecistolitíase , Coledocolitíase , Laparoscopia , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Adulto , Idoso , Idoso de 80 Anos ou mais , Coledocolitíase/cirurgia , Coledocolitíase/etiologia , Estudos Retrospectivos , Colecistolitíase/complicações , Colecistolitíase/cirurgia , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Resultado do Tratamento , Ducto Colédoco/cirurgia , Laparoscopia/métodos
10.
ACS Nano ; 16(10): 17424-17434, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36239245

RESUMO

Fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) region holds great promise for in vivo bioimaging. However, it is challenging to develop a brilliant donor-acceptor-donor (D-A-D) type NIR-II fluorophore with maximal absorption beyond 1000 nm in aqueous solution. Herein, we report a bright D-A-D type BOIMPY-based NIR-II dye (NK1143) with peak absorption/emission at 1005/1143 nm for in vivo bioimaging. Co-assembly of NK1143, SC12 (intermolecular steric hindrance modulator), and DSPE-PEG2000 effectively inhibits H-aggregation of NK1143 in aqueous solution and enhances the brightness simultaneously up to 53-fold by leveraging synergistic steric regulation strategy. Notably, this strategy allows for deep optical penetration of 8 mm and high-resolution blood vessels imaging in vivo, displaying high signal-to-background ratio of 7.8/1 under 980 nm excitation. More importantly, the BOIMPY-based nanoprobe can passively target and clearly visualize broad types of tumor xenografts, further improving intraoperative NIR-II fluorescence-guided resection of tiny metastases of less than 1 mm. This work provides an effective strategy for the development of BOIMPY-based NIR-II organic fluorophores with broad applications.


Assuntos
Neoplasias , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Corantes Fluorescentes , Imagem Óptica
11.
Small ; 18(49): e2204851, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36300919

RESUMO

It is challenging to develop a near-infrared (NIR) small molecular photosensitizer for synergistic phototherapy in deep tissues. Herein, first, a heavy-atom-free NIR hemicyanine photosensitizer (BHcy) for 808 nm light-mediated synergistic photodynamic therapy/photothermal therapy (PDT/PTT) anticancer therapy by leveraging the acceptor engineering strategy is reported. This strategy endows BHcy with a more planar and larger π-conjugated structure, resulting in long NIR absorption/emission at 770/915-1200 nm as well as enhanced singlet oxygen (1 O2 ) generation ability and photothermal effect, which is ascribed to the reduced energy levels of excited singlet/triplet states and the promoted intersystem crossing process. Notably, BHcy-based nanoparticles (BHcy-NPs) exhibit efficient 1 O2 yield (12.9%) and high photothermal conversion efficiency (55.1%). More importantly, BHcy-NPs are able to significantly kill cancer cells by destroying main organelles and inhibit tumor growth in vivo after a single irradiation. Overall, this study provides a strategy to design new heavy-atom-free PDT/PTT agents for potential clinical applications.


Assuntos
Terapia Fototérmica
12.
Onco Targets Ther ; 15: 891-896, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046466

RESUMO

Background: Periampullary carcinoma, which includes ampullary carcinoma, pancreatic head cancer, distal common bile duct cancer, and duodenal papillary cancer, is a relatively rare malignancy with uncertain therapeutic options. Although several studies have investigated the efficacy of multiple adjuvant chemotherapy regimens for periampullary carcinoma treatment, the optimal regimen remains to be determined. The inherent heterogeneity of the mucosal origin divides periampullary carcinoma into intestinal and pancreaticobiliary types. Therefore, the selection of chemotherapy regimens based on pathological type may have potential therapeutic significance. Case Presentation: A 72-year-old woman with moderately differentiated periampullary adenocarcinoma experienced disease progression after receiving FOLFOX regimen. Subsequently, the sample was subtyped first by H&E evaluation and then by the evaluation of an IHC panel composed of CK20, CDX2, MUC1, MUC2, and MUC5AC. The pathologists concluded that the patient's sample was of the pancreaticobiliary (PB) subtype. The subsequent change to gemcitabine plus S-1 adjuvant therapy achieved remission of liver metastases based on the pathological classification of the cancer. Conclusion: Based on the pathological classification, adjuvant chemotherapy with gemcitabine may be beneficial for patients with PB subtype periampullary carcinoma. 5-Fu-based adjuvant chemotherapy may be beneficial for patients with intestinal subtype periampullary carcinoma.

13.
Anal Chem ; 94(39): 13556-13565, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36124440

RESUMO

Simultaneous detection of different diseases via a single fluorophore is challenging. We herein report a bichromatic fluorophore named Cy-914 for the simultaneous diagnosis of non-alcoholic fatty liver disease (NAFLD) and metastatic intestinal cancer by leveraging its NIR-I/NIR-II dual-color imaging capability. Cy-914 with a pKa of 6.98 exhibits high sensitivity to pH and viscosity, showing turn-on NIR-I fluorescence at 795 nm in an acidic tumor microenvironment, meanwhile displaying intense NIR-II fluorescence at 914/1030 nm under neutral to slightly basic viscous conditions. Notably, Cy-914 could sensitively and noninvasively monitor viscosity variations in the progression of NAFLD. More importantly, it was able to simultaneously visualize NAFLD (ex/em = 808/1000-1700 nm) and intestinal metastases (ex/em = 570/810-875 nm) in two independent channels without spectral cross interference after topical spraying, further improving fluorescence-guided surgery of tiny metastases less than 3 mm. This strategy may provide an understanding for developing multi-color fluorophores for multi-disease diagnosis.


Assuntos
Neoplasias Intestinais , Hepatopatia Gordurosa não Alcoólica , Carbocianinas , Corantes Fluorescentes , Humanos , Neoplasias Intestinais/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Imagem Óptica/métodos , Microambiente Tumoral
14.
Huan Jing Ke Xue ; 43(3): 1404-1413, 2022 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-35258204

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are of concern globally because of their carcinogenic, teratogenic, mutagenic, and bio-accumulative effects. Northern China is one of the regions in China with a high density of lakes; however, the lake aquatic environment is becoming seriously deteriorated, especially from PAH pollution due to the intensification of human activities during the past 100 years. Therefore, the spatial distribution and historical changes in PAHs in lake sediments from northern China were analyzed to indicate their response to anthropogenic emissions and pollution reduction actions. The ω(PAHs) in lake sediments ranged from 18.2 to 1205.0 ng·g-1, and low molecular weight PAHs were the dominant compounds. PAH concentrations increased from the 1950s to a peak level in the 2000s, which was induced mainly by increased energy consumption and rapid economy development, with PAH levels decreasing subsequently in the last 10 years due to craft improvement of wastewater treatment plants and the promotion of new energy policies. Spatially, PAHs pollution in Northeast and North China was more serious than that in Northwest China due to the higher level of economic development and energy consumption. Source apportionment results revealed that historical PAH emissions transferred from biomass combustion to a mixture of coal and petroleum combustion. In addition, the results of ecological risk assessment showed that the synthetic sediment quality index (SeQI) of northern China ranged from 36 to 75, and North and Northeast China posed higher ecological risk than that in Northwest China, with phenanthrene (Phe), acenaphthylene (Ace), acenaphthylene (Acy), and dibenzo(a,h)anthracene (DahA) as the main risk contributors.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , China , Monitoramento Ambiental , Sedimentos Geológicos , Atividades Humanas , Humanos , Lagos , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise
15.
J Minim Access Surg ; 18(2): 254-259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34259212

RESUMO

BACKGROUND: The aim of the study was to compare the benefits and drawbacks of laparoscopic left hepatectomy (LLH) in patients with previous abdominal surgery (PAS) with those in patients without PAS and confirm the safety and feasibility of LLH as a treatment for patients with hepatolithiasis and PAS. MATERIALS AND METHODS: This retrospective comparative study included 111 patients who underwent LLH for hepatolithiasis (with PAS, n = 41; without PAS, n = 70) from August 2017 to August 2019. Patients' general information, surgical outcomes, hospital stay duration, hospitalisation cost, post-operative laboratory data and post-operative complications were evaluated. RESULTS: No statistically significant difference was noted in the post-operative laboratory data between patients with and without PAS (P > 0.05). Longer operative times were required for patients with PAS than for those without PAS (P = 0.025). Hospitalisation cost, hospital stay duration, blood loss, open conversion and post-operative complications were not significantly different between patients with and without PAS (P > 0.05). No cases of mortality were noted. CONCLUSIONS: LLH is a safe and feasible treatment for patients with hepatolithiasis and PAS.

16.
FEBS J ; 289(10): 2809-2827, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34919331

RESUMO

Phagocytic clearance of apoptotic germ cells (GCs), as well as residual bodies released from developing spermatids, is critical for Sertoli cells (SCs) to maintain inner environment homeostasis within the testis. However, the molecular mechanisms controlling the phagocytosis are ill defined. Here, we identify a new role for alpha-enolase (ENO1), a key enzyme during glycolysis, as a molecule that facilitates testicular phagocytosis via transactivation of the engulfment and cell motility 1 (Elmo1) gene. Using immunohistochemistry and double-labeling immunofluorescence, ENO1 was observed to be expressed exclusively in the nuclei of SCs and its expression correlated with the completion of SC differentiation. By incubating TM4 cells with different pharmacological inhibitors and establishing TM4Tnfr1-/- cells, we demonstrated that SC-specific expression of ENO1 was under a delicate paracrine control from apoptotic GCs. In turn, persistent blockade of ENO1 expression by a validated small interfering RNA protocol resulted in the disturbance of spermatogenesis and impairment of male fertility. Furthermore, using ChIP, electrophoretic mobility shift and luciferase reporter assays, we showed that, in the presence of apoptotic GCs, ENO1 binds to the distal region of the Elmo1 promoter and facilitates transactivation of the Elmo1 gene. In agreement, overexpression of ELMO1 ameliorated ENO1 deficiency-induced impairment of phagocytosis in TM4 cells. These data reveal a novel role for SC-specific expression of ENO1 in regulating phagocytosis in testis, identify tumor necrosis factor-α and ELMO1 as critical upstream and downstream factors in mediating ENO1 action, and have important implications for our understanding of paracrine control of SC function by adjacent GCs.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Fosfopiruvato Hidratase , Células de Sertoli , Testículo , Fator de Necrose Tumoral alfa , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Movimento Celular , Expressão Gênica , Masculino , Camundongos , Fagocitose/genética , Fosfopiruvato Hidratase/metabolismo , Células de Sertoli/citologia , Testículo/citologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
17.
ACS Cent Sci ; 7(12): 2039-2048, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34963896

RESUMO

We herein report a series of high-brightness pH-activatable near-infrared (NIR) BODIPY probes for high-contrast intravital imaging of deep-seated early breast cancer bone metastasis by harnessing the axial substituent effect. These probes exhibit tunable pK a, higher brightness, and antiquenching capabilities in aqueous solution, which can be simultaneously adjusted by axial steric substituents. The optimized probe BODO-3 bearing axial dimethyl substituents exhibited a higher pK a value of 5.6 and a brighter NIR fluorescence under tumor acidic pH, showing 10.3-fold and 6.5-fold enhanced brightness (εΦ) at pH 5.5 and 6.5, respectively. Due to the higher brightness, BODO-3 with a brilliant NIR emission at 700 nm allows for deep optical penetrations of 5 and 8 mm at pH 6.5 and 4.5, respectively. Meanwhile, covalent functionalization with glucose (BODO-3-Glu) could further enhance breast cancer and its soft tissue metastasis imaging in vivo. Notably, covalent functionalization with bisphosphonate (BODO-3-PO 3 H 2 ) allowed the successful targeting and visualization of deep-seated bone metastases of breast cancer with a high tumor to normal contrast of 8/1, outperforming X-rays in early detection. This strategy may provide insights for designing high-brightness activatable NIR probes for detecting deep-seated tumors and metastases.

18.
Chem Commun (Camb) ; 57(81): 10636-10639, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34581325

RESUMO

A series of pH-activatable aza-BODIPY-based fluorescent probes were developed for rapid cancer visualization and real-time fluorescence-guided surgery by harnessing topical spraying. These probes exhibited good water-solubility, a tunable pKa from 5.0 to 7.9, and stable intense NIR emission at ∼725 nm under acidic conditions. AzaB5 with a pKa value of 6.7 was able to rapidly and clearly visualize pulmonary and abdominal metastatic tumours including tiny metastases less than 2 mm via topical spraying, further improving intraoperative fluorescence-guided resection. We believe that AzaB5 is promising as a powerful tool to rapidly delineate a broad range of malignancies and assist surgical tumour resection.


Assuntos
Compostos Aza/química , Compostos de Boro/química , Neoplasias da Mama/diagnóstico por imagem , Fluorescência , Corantes Fluorescentes/química , Administração Tópica , Animais , Compostos Aza/administração & dosagem , Compostos de Boro/administração & dosagem , Neoplasias da Mama/cirurgia , Linhagem Celular Tumoral , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/síntese química , Concentração de Íons de Hidrogênio , Camundongos , Estrutura Molecular , Imagem Óptica
19.
Huan Jing Ke Xue ; 42(10): 4727-4738, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581115

RESUMO

Shengjin Lake, which serves as an important National Nature Reserve, is suffering from chemical pollution due to rapid industrial and agricultural development in the circumjacent basin. Therefore, 168 anthropogenic toxic chemicals were determined to examine their spatial distribution and identify priority pollutants using a ranking system based on occurrence(O), persistence(P), bioaccumulation(B), ecological risk(E), and human health risk(H). Ecosystem and human health risks were also assessed. The spatial distribution of pollutants indicated that higher concentrations occur in the upper lake area compared to the middle and lower lake areas because of Jiang Dam. According to the derived priority pollutant list, phthalate esters(PAEs), organochlorine pesticides(OCPs), and heavy metals(HMs) are high-priority pollutants; polychlorinated biphenyls(PCBs), polycyclic aromatic hydrocarbons(PAHs), and volatile organic compounds(VOCs) are medium-priority pollutants; and antibiotics(ANTs) are low-priority pollutants. The ecology risk quotient(RQ) of the high-priority pollutants ranged from 4.3 to 15.9, indicating severe ecology risk to the aquatic organism, and higher risks were found in the upper lake areas. Additionally, the human health risk assessment revealed negligible carcinogenic risks associated with high-priority pollutants. The comprehensive ranking system established in this study can be applied to other lake basins by altering the measured concentrations to screen for priority pollutants, offering a scientific foundation for identifying priority control pollutants for watershed management.


Assuntos
Poluentes Ambientais , Hidrocarbonetos Clorados , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , China , Ecossistema , Monitoramento Ambiental , Humanos , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco , Água , Poluentes Químicos da Água/análise
20.
Oncol Rep ; 45(2): 793, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33416162

RESUMO

Following the publication of the above article, the authors have realized that Fig. 5A was published with certain errors; essentially, the authors needed to perform further experiments to validate certain of their results, and the Blank and si­NC control data in Fig. 5A were included from an incorrect set of experiments (the intended si­NUSAP1 experimental data from the flow cytometric analyses, however, were presented correctly in the published Figure). The corrected version of Fig. 5, featuring the panels for the Blank and si­NC control data in Fig. 5A from the same set of experiments, is shown opposite. The authors have confirmed that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum. Furthermore, they apologize to the readership of the Journal for any inconvenience caused. [the original article was published in Oncology Reports 36: 1506-1516, 2016; DOI: 10.3892/or.2016.4955].

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