Brain tumor segmentation using U-Net in conjunction with EfficientNet.

According to the Ten Leading Causes of Death Statistics Report by the Ministry of Health and Welfare in 2021, cancer ranks as the leading cause of mortality. Among them, pleomorphic glioblastoma is a common type of brain cancer. Brain cancer often occurs in the brain with unclear boundaries from normal brain tissue, necessitating assistance from experienced doctors to distinguish brain tumors before surgical resection to avoid damaging critical neural structures. In recent years, with the advancement of deep learning (DL) technology, artificial intelligence (AI) plays a vital role in disease diagnosis, especially in the field of image segmentation. This technology can aid doctors in locating and measuring brain tumors, while significantly reducing manpower and time costs. Currently, U-Net is one of the primary image segmentation techniques. It utilizes skip connections to combine high-level and low-level feature information, leading to significant improvements in segmentation accuracy. To further enhance the model's performance, this study explores the feasibility of using EfficientNetV2 as an encoder in combination with U-net. Experimental results indicate that employing EfficientNetV2 as an encoder together with U-net can improve the segmentation model's Dice score (loss = 0.0866, accuracy = 0.9977, and Dice similarity coefficient (DSC) = 0.9133).

In vivo evaluation of liver function by multimodal imaging in an alcohol-induced liver injury model.

Background: Visually evaluating liver function is a hot topic in hepatology research. There are few reliable and practical visualization methods for evaluating the liver function in vivo in experimental studies. In this study, we established a multimodal imaging approach for in vivo liver function evaluation and compared healthy mice with chronic alcoholic liver injury (cALI) model mice to explore its potential applicability in experimental research. Methods: In vivo fluorescence imaging (IVFI) technology was utilized to visually represent the clearance of indocyanine green from the liver of both healthy mice and mice with cALI. The reserve liver function was evaluated via IVFI using the Cy5.5-galactosylated polylysine probe, which targets the asialoglycoprotein receptor of hepatocytes. Hepatic microcirculation was assessed through laser speckle perfusion imaging of hepatic blood perfusion. The liver microstructure was then investigated by in vivo confocal laser endomicroscopy imaging. Finally, hepatic asialoglycoprotein receptor expression, histology, and the levels of serum alanine aminotransferase and aspartate aminotransferase were measured. Results: In vivo multimodal imaging results intuitively and dynamically showed that indocyanine green clearance [mean ± standard deviation (SD): 30.83±14.71, 95% confidence interval (CI): 20.3 to 41.35], the fluorescence signal intensity (mean ± SD: 1,217.92±117.63; 95% CI: 1,148.38 to 1,290.84) and fluorescence aggregation area (mean ± SD: 5,855.80±1,271.81; 95% CI: 5,051.57 to 6,653.88) of Cy5.5-galactosylated polylysine targeting the asialoglycoprotein receptor, and hepatic blood perfusion (mean ± SD: 1,494.86±299.33; 95% CI: 1,316.98 to 1,690.16) in model mice were significantly lower than those in healthy mice (all P<0.001). Compared to healthy mice, the model mice exhibited a significant decline in liver asialoglycoprotein receptor expression (mean ± SD: 219.03±16.34; 95% CI: 208.97 to 230.69; P<0.001), increased serum alanine aminotransferase (mean ± SD: 149.70±47.89 U/L; 95% CI: 81.75 to 128.89; P=0.01) and aspartate aminotransferase levels (mean ± SD: 106.30±36.13 U/L; 95% CI: 122.01 to 180.17; P=0.021), hepatocyte swelling and deformation, disappearance of the hepatic cord structure, partial necrosis, and disintegration of hepatocytes. The imaging features of fluorescence signals in liver regions, hepatic blood perfusion and microstructure were biologically related to hepatic asialoglycoprotein receptor expression, serum indices of liver function, and histopathology in model mice. Conclusions: Utilizing in vivo multimodal imaging technology to assess liver function is a viable approach for experimental research, providing dynamic and intuitive visual evaluations in a rapid manner.

Case report: A de novo ERBB3 mutation develops in a gallbladder cancer patient carrying BRCA1 mutation after effective treatment with olaparib.

Background: Gallbladder cancer (GBC) is highly lethal and resistant to most chemotherapeutic drugs. GBC was reported to carry multiple genetic mutations such as TP53, K-RAS, and ERBB2/3. Here, we unexpectedly identified a patient with GBC harboring germline BRCA1 p.Arg1325Lys heterozygous mutation. We sought to determine if olaparib, the poly ADP-ribose polymerase inhibitor (PARPi) commonly treated for BRCA mutation, can inhibit cancer development via a therapeutic trial on this patient. Case presentation: The patient received GBC R0 resection after an 8-week olaparib treatment. After surgery and 6-month follow-up treatment with olaparib, the patient's blood carbohydrate antigen 19-9 (CA19-9) level declined from 328 to 23.6 U/ml. No recurrence in CT scanning was observed, indicating a disease-free survival of 6 months with conventional therapy. Two months later, CT examination and CA19-9 level showed cancer relapse. A blood biopsy revealed a new ERBB3 p.Gly337Arg mutation. GBC cell lines ectopically expressing BRCA1 p.Arg1325Lys together with ERBB3 p.Gly337Arg mutations were challenged with olaparib and/or afatinib, an ERBB2/3 inhibitor. The dual mutation cells were more responsive to the combined olaparib with afatinib than a single drug in the cell proliferation assay. Conclusion: Olaparib is effective in a GBC patient with a BRAC1 mutation. The efficacy of olaparib and afatinib in both cultured BRAC1 and ERBB3 mutation cell lines suggests that a combined regimen targeting BRCA1/2 and ERBB2/3 mutations may be an optimal strategy to treat GBC patients who carry both gene mutations.

Effects of electroacupuncture on liver function in mice with chronic alcoholic liver injury: visual display by in vivo fluorescence imaging.

OBJECTIVE: Acupuncture can improve the symptoms of alcohol-induced bodily injury and has been accepted by the World Health Organization. In this study, in vivo fluorescence imaging (IVFI) was applied to display and evaluate the effect of electroacupuncture (EA) on liver function (LF) in mice with chronic alcoholic liver injury (cALI). METHODS: IVFI of the Cy5.5-galactosylated polylysine (Cy5.5-GP) probe targeting the liver asialoglycoprotein receptor (ASGPR) and liver indocyanine green (ICG) clearance was performed to visually evaluate the effect of EA at ST36 and BL18 on liver reserve function and hepatic metabolism in mice with cALI. In addition, changes in ASGPR expression, serum indexes of LF, and hepatic morphology were observed. RESULTS: After EA at ST36 and BL18, the ASGPR-targeted fluorescence signals (FS) in the liver increased significantly in cALI mice (p < 0.05) and exhibited relationships with liver ASGPR expression, liver ICG clearance, liver histology, and serum marker levels of LF in cALI mice undergoing EA intervention. CONCLUSIONS: As displayed by IVFI, EA at ST36 and BL18 appears to improve liver reserve function and inhibit the development of liver injury in mice with cALI. EA may have potential as a treatment strategy to protect against ALI.

Application of membrane anatomy in hepatopancreatobiliary and splenic surgery / 中华外科杂志

Understanding of a variety of membranous structures throughout the body,such as the fascia,the serous membrane,is of great importance to surgeons. This is especially valuable in abdominal surgery. With the rise of membrane theory in recent years,membrane anatomy has been widely recognized in the treatment of abdominal tumors,especially of gastrointestinal tumors. In clinical practice. The appropriate choice of intramembranous or extramembranous anatomy is appropriate to achieve precision surgery. Based on the current research results,this article described the application of membrane anatomy in the field of hepatobiliary surgery,pancreatic surgery,and splenic surgery,with the aim of blazed the path from modest beginnings.

A sustainable mouse karyotype created by programmed chromosome fusion.

Chromosome engineering has been attempted successfully in yeast but remains challenging in higher eukaryotes, including mammals. Here, we report programmed chromosome ligation in mice that resulted in the creation of new karyotypes in the lab. Using haploid embryonic stem cells and gene editing, we fused the two largest mouse chromosomes, chromosomes 1 and 2, and two medium-size chromosomes, chromosomes 4 and 5. Chromatin conformation and stem cell differentiation were minimally affected. However, karyotypes carrying fused chromosomes 1 and 2 resulted in arrested mitosis, polyploidization, and embryonic lethality, whereas a smaller fused chromosome composed of chromosomes 4 and 5 was able to be passed on to homozygous offspring. Our results suggest the feasibility of chromosome-level engineering in mammals.

Clinical application of bipolar tweezers-clamp for hepatic parenchymal transection / 中华外科杂志

Objective: To investigate the clinical value of the bipolar tweezers-clamp for the hepatic parenchymal transection in the resection of hepatocellular carcinoma. Methods: From January 2020 to January 2021,63 patients with the hepatocellular carcinoma for hepatectomy at Department of Hepatopancreatobiliary Surgery,Yuebei People's Hospital Affiliated to Shantou University Medical College were analyzed retrospectively.According to the different instruments used in the hepatic parenchymal transection,the patients were divided into bipolar tweezers-clamp group and ultrasonic scalpel group.There were 32 patients in bipolar tweezers-clamp group,with age of (55.5±10.5)years(range:37 to 78 years),including 22 males and 10 females,tumor size was (6.0±3.4)cm(range:2.4 to 13.4 cm). There were 6 patients with portal vein tumor thrombus and 5 patients with portal hypertension. There were 31 patients in ultrasonic scalpel group,with aged(57.8±10.1)years(range:37 to 79 years),including 27males and 4 females,tumor size was(7.9±5.1)cm(range: 2.4 to 21.3 cm),3 patients with portal vein tumor thrombus and 2 patients with portal hypertension. The preoperative baseline data,operation time,blood loss,postoperative liver function and the complications were compared between two groups using t test,χ2 test and Fisher exact probabilityrespectively. Results: The operation was successfully completed in both groups.Compared with the ultrasonic scalpel group,the operation time was significantly shorter((219.3±76.4)minutes vs.(294.0±100.8)minutes,t=-3.322,P=0.002),the blood loss was less((250(475)ml vs. 500(1 050)ml,t=-2.307,P=0.026),the concentrate red blood cells transfusion volume was less(0.92(0.88)U vs. 2.32(4.00)U,Z=-1.987,P=0.047) in the bipolar tweezers-clamp group.The postoperative serum ALB level was higher in the bipolar tweezers-clamp group than that in the ultrasonic scalpel group((33.5±6.1)g/L vs. (29.5±4.2)g/L,t=3.226,P=0.020) on postoperative day 1;((35.7±4.5)g/L vs.(30.1±3.2)g/L,t=5.575,P<0.01) on postoperative day 3;((33.2±3.7)g/L vs. (31.0±4.4)g/L,t=3.020,P=0.004) on postoperative day 7. There was no significant difference in serum ALT,TBIL and PT level between the two groups(all P>0.05).No postoperative bile leakage occurred in both groups.The postoperative complications occurred in 8 cases(25.0%)in the bipolar tweezers-clamp group,including liver failure in one,and in 11 cases(35.5%)in the ultrasonic scalpel group,including liver failure in two(P>0.05). Conclusion: The bipolar tweezers-clamp is a safe and reliable method for the hepatic parenchymal transaction,which is quick and less bleeding during the hepatic resection.

Ten-year retrospect of ALPPS in the treatment of hepatocellular carcinoma:an eternal concept with cautious technologic choice / 中华外科杂志

Clinical practice using associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) or its modified procedures in treatment of primary hepatocellular carcinoma(HCC) with insufficient future liver remnant(FLR) in the past 10 years has failed to meet our expectations both in achieving decreased perioperative complications and mortality.The efficacy of ALPPS in improving long-term survival outcome of HCC still remains poor.Due to the trauma of two surgery within a short period,and patients with inadequate FLR are all diagnosed at advanced disease stages,ALPPS can only achieve surgical rather than biological tumor-curability.Previous studies have demonstrated comparable 5-year survival rates between early and advanced stages of HCC who underwent regional treatments.Therefore,tumor biological conversion is the key strategy prior to liver remnant volume conversion in improving treatment outcomes for HCC patients with insufficient FLR.Target therapy,immunotherapy together with locally treatment were expected to improve the conversion efficacy.Looking back at the development of ALPPS for the last decade,the rapid proliferation of FLR should be passed on,while the technology costs high risks and result in poor long-term outcome must be cautiously selected.

[Effect of electroacupuncture on the hemorheology and hepatic microcirculation in mice with chronic alcoholic liver injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the hemorheology and hepatic microcirculation in mice with chronic alcoholic liver injury (cALI), so as to explore the microcirculation mechanism of EA underlying regulating liver function in cALI mice. METHODS: Forty Kunming mice were randomly assigned to control, model, acupoint EA and non-acupoint EA groups, with 10 mice in each group. The cALI model was established by gavage with 50% ethanol (15 mL/kg，2 times per day with 8 hours' interval) for 28 d. Mice in the acupoint EA group received EA at bilateral "Zusanli" (ST36) and "Ganshu"(GB11) for 20 min, once daily for 14 d. And mice in the non-acupoint EA group received EA the spot about 1 cm lateral to GB11 and 0.5 cm lateral to ST36 respectively for 20 min, once daily for 14 d. The hepatic blood perfusion (HBP) of mice was detected by laser speckle perfusion imaging. The index of hemorheology, serum markers of liver function and hepatic histology in mice were observed by automatic blood rheometer, automatic bio-analysis machine and H.E. staining, respectively. RESULTS: Compared with the control group, the HBP of the model group was significantly decreased (P<0.05); the low-cut whole blood viscosity, plasma viscosity, and erythrocyte sedimentation level were significantly increased （P<0.05）, and the red blood cell deformation index was significantly decreased (P<0.05); serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) increased significantly (P<0.05) in the model group. Hepatocyte steatosis accompanied by inflammatory cell infiltration and focal necrosis was observed in the model group. After EA at ST36 and GB11, and in comparison with the model group showed that the HBP was significantly increased (P<0.05); the low-cut whole blood viscosity, plasma viscosity, erythrocyte sedimentation rate and serum GGT were significantly decreased (P<0.05), and the red blood cell deformation index was significantly increased (P<0.05）; the degree of fatty degeneration in the liver tissue was reduced, and the focal necrosis was reduced. The plasma viscosity, erythrocyte sedimentation rate were significantly decreased (P<0.05), and the red blood cell deformation index was significantly increased in the non-acupoint EA group relevant to the model group (P<0.05). The erythrocyte sedimentation rate and the red blood cell deformation index of the acupoint EA group was significantly lower than that of the non-acupoint EA group (P<0.05). CONCLUSION: EA at ST36 and GB11 could improve the hemorheological disorder and the hepatic microcirculation, and inhibit the deve-lopment of liver injury in cALI mice.

Influence of CYP2D6 gene polymorphisms on the pharmacokinetics of aripiprazole in healthy Chinese subjects.

Background: Pharmacogenetics study was added into 2 bioequivalence trials of aripiprazole. The correlation between CYP2D6 polymorphisms and aripiprazole pharmacokinetics (PK) was analyzed. Materials & methods: A total of 140 subjects were included. A total of 26 CYP2D6 gene alleles were detected. The plasma concentration of aripiprazole was measured by liquid chromatography-tandem mass spectrometry. SPSS Statistics 21 was used to analyze the correlation between CYP2D6 polymorphisms and aripiprazole PK parameters. Results: All of the four PK parameters were significantly influenced by CYP2D6rs1058164 and rs28371699. t1/2 and area under the concentration-time curve exhibited significant difference between CYP2D6 extensive metabolizers and intermediate metabolizers. Conclusion: Aripiprazole PK was greatly influenced by CYP2D6. Attention should be paid to the possible dose adjustment for CYP2D6 intermediate metabolizer population when the drug is used in Chinese patients.

Patient-centered developments in colon- and rectal cancer with a multidisciplinary international team: From translational research to national guidelines.

Rarely, scientific developments centered around the patient as a whole are published. Our multidisciplinary group, headed by gastrointestinal surgeons, applied this research philosophy considering the most important aspects of the diseases "colon- and rectal cancer" in the long-term developments. Good expert cooperation/knowledge at the Comprehensive Cancer Center Ulm (CCCU) were applied in several phase III trials for multimodal treatments of primary tumors (MMT) and metastatic diseases (involving nearly 2000 patients and 64 centers), for treatment individualization of MMT and of metastatic disease, for psycho-oncology/quality of life involving the patients' wishes, and for disease prevention. Most of the targets initially were heavily rejected/discussed in the scientific communities, but now have become standards in treatments and national guidelines or are topics in modern translational research protocols involving molecular biology for e.g., "patient centered individualized treatment". In this context we also describe the paths we had to tread in order to realize our new goals, which at the end were highly beneficial for the patients from many points of view. This description is also important for students and young researchers who, with an actual view on our recent developments, might want to know how medical progress was achieved.

Influence of dietary factors on radius speed of sound in female college students / 中国学校卫生

Objective@#To understand the level of radius speed of sound (SOS) in female college students and explore the effect of dietary on their bone health,so as to provide a reference for effective prevention fracture and osteoporosis among college students.@*Methods@#A total of 363 female college students were selected by multistage stratified random sampling method. Dietary intake was assessed with a self-administered food frequency questionnaire, principal component analysis was used to derive dietary patterns. Speed of sound was measured by ultrasonic bone densitometer.@*Results@#In all, the mean SOS of female college students was(4 138.0±114.3)m/s, 26.7% of female college students had low bone mass. Three dietary patterns were identified by factor analysis, explaining 55.4% of the diet variation: "snack" "plant" "high protein and high fat" patterns, respectively. Multiple linear regression analysis showed that with the increase of age, the level of SOS in radius increased significantly; and snacks consumption was negatively associated with the level of SOS(β=13.23, -0.47, P<0.05).@*Conclusion@#University stage is still the critical period of bone mass accumulation for female, snacks consumption may have a negative impact on bone health, so it is necessary to carry out nutrition education to help improve health awareness, promote health eating, and lead health lives to prevent osteoporosis.

[Effect of electroacupuncture on liver surface blood perfusion and related indexes of oxidative stress in mice with acute alcoholic liver injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on liver surface blood perfusion and related indexes of oxidative stress in mice with acute alcoholic liver injury （AALI）, so as to explore its mechanism underlying improving of AALI. METHODS: Twenty-four Kunming mice were randomly divided into control, model and EA groups (8 mice/group). AALI model was established by intragastric administration of 50% ethanol at 6 g/kg. EA (4-6 V, 50 Hz) was applied to bilateral"Zusanli"(ST36) and"Taichong"(LR3) for 30 min. The liver surface blood perfusion was dynamically observed by moorFLPI laser speckle imager for 30 min. The morphological changes of the liver tissue were determined by H.E. staining. Levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the liver were measured by ELISA. RESULTS: Compared with the control group, the model group had markedly pathological changes of the hepatic cords, hepatic sinuses and hepatocytes shown by H.E. staining, a significant reduction in liver surface blood perfusion and the content of SOD in liver tissue (P<0.01, P<0.05), and a significant increase in the content of MDA in liver tissue (P<0.05). Compared with the model group, H.E. staining showed reduced pathological changes of the liver tissue, meanwhile the liver surface blood perfusion significant increased (P<0.05) and the content of MDA in liver tissue significantly decreased (P<0.01) in the EA group. CONCLUSION: EA can improve the liver surface circulation of AALI mice, and regulate the oxidative stress response, and thus help to repair the damage of liver tissue.

Surgical indication and strategy for liver hemangioma in the caudate lobe: a multi-institutional retrospective analysis with 137 patients.

OBJECTIVE: To investigate the surgical indication and tactics for liver hemangioma in the caudate lobe METHODS: From January 1994 to July 2019, 137 patients, including 51 males and 86 females with the average age of 49.2 years old were diagnosed with liver hemangioma in caudate lobe and received treatment at five tertiary referral hospitals. Clinical features, correlations between tumor size and clinical manifestations, treatments, and prognosis were analyzed. RESULTS: Of the 137 patients identified, 40 (29.20%) patients were asymptomatic, whereas other 94 patients had clinical symptoms mainly presented as upper abdominal discomfort, epigastric distention, upper abdominal dull pain, nausea, and vomiting. Fifteen (93.75%), 18 (39.13%), and 7 (10.45%) patients presented no clinical symptoms among those tumor size was less than 3 cm (D ≤ 3 cm, n = 16), 3 cm < D ≤ 6 cm (n = 46), and 6 cm < D ≤ 9 cm (n = 67), respectively, while all 8 patients with tumor larger than 9 cm were symptomatic. Tumor diameter was obviously associated with the presence of clinical symptoms. In follow-up period, 7 patients in the conservative group (n = 39) received surgery because of tumor growth or symptom appearance. Totally 105 patients received operation including partial resection or isolated complete resection of caudate lobe and caudate lobe resection combined with liver segment resection, right liver resection, or left liver resection. All operations went smoothly, and no severe complications appeared. CONCLUSION: Tumor diameter was obviously associated with the presence of clinical symptoms in patients with hemangioma in caudate lobe. Surgical therapy is not recommended for asymptomatic patients and available for patient who has symptoms. Effective surgical strategies should be put into use to reduce operative bleeding.

Percutaneous Isthmus Foraminoplasty and Full-Endoscopic Lumbar Discectomy for Very Highly Upmigrated Lumbar Disc Herniation: Technique Notes and 2 Years Follow-Up.

OBJECTIVE: To report the technical notes and clinical outcome of percutaneous isthmus foraminoplasty and full-endoscopic lumbar discectomy (PIF-FELD) for the treatment of very highly upmigrated lumbar disc herniation (VHUM-LDH). PATIENTS AND METHODS: From January 2014 to December 2017, 16 patients with VHUM-LDH underwent PIF-FELD surgery. A 10-mm-diameter semi-open foraminoplasty was performed on the dorsal side of the upper intervertebral foramen with lateral isthmus resection by a safe trephine system, in which the facet joint was not injured. Full-endoscopic transforaminal fragmentectomy in the spinal canal and discectomy in the intervertebral space were performed simultaneously. Magnetic resonance imaging of the lumbar spine was reexamined on the second day and 3 months after the operation to evaluate the completeness of the disc fragmentectomy and nerve decompression. The patients were followed up on the visual analog scale (VAS) of lumbar pain and leg pain and Oswestry Disability Index on the second day, 3 months, 6 months, 1 year, and 2 years after operation. The MacNab score and nerve root function recovery were evaluated at 2 years postoperative follow-up. RESULTS: All operations were successfully completed without any change in the surgical method. During the operation, 5 patients were found to have a single sequestered fragment, and the remaining 11 patients had multiple sequestered fragments. There were no complications (e.g., dural tear and nerve injury) during the operation, and no complications (e.g., infection, cerebrospinal fluid leakage, exacerbation of nerve root function injury, and recurrence of intervertebral disc herniation) occurred. Postoperative reexamination of lumbar magnetic resonance imaging in all patients showed complete disc fragmentectomy and adequate nerve decompression. The postoperative low back pain VAS and leg pain VAS scores and Oswestry Disability Index on the second day, 3 months, 6 months, 1 year, and 2 years after operation were significantly improved compared with preoperatively (P < 0.01). At 2 years follow-up, the sensation and muscular strength of the affected nerve root innervation area were significantly restored (P < 0.05), but tendon reflex function was not significantly restored (P > 0.05). At 2 years follow-up, MacNab scores included 6 excellent, 9 good, and 1 fair. CONCLUSIONS: PIF-FELD is a safe and effective minimally invasive spine surgery technique for VHUM-LDH.

Palladium supported on triazolyl-functionalized hypercrosslinked polymers as a recyclable catalyst for Suzuki-Miyaura coupling reactions.

A novel hypercrosslinked polymers-palladium (HCPs-Pd) catalyst was successfully prepared via the external cross-linking reactions of substituted 1,2,3-triazoles with benzene and formaldehyde dimethyl acetal. The preparation of HCPs-Pd has the advantages of low cost, mild conditions, simple procedure, easy separation and high yield. The catalyst structure and composition were characterized by N2 sorption, TGA, FT-IR, SEM, EDX, TEM, XPS and ICP-AES. The HCPs were found to possess high specific surface area, large micropore volume, chemical and thermal stability, low skeletal bone density and good dispersion for palladium chloride. The catalytic performance of HCPs-Pd was evaluated in Suzuki-Miyaura coupling reactions. The results show that HCPs-Pd is a highly active catalyst for the Suzuki-Miyaura coupling reaction in H2O/EtOH solvent with TON numbers up to 1.66 × 104. The yield of biaryls reached 99%. In this reaction, the catalyst was easily recovered and reused six times without a significant decrease in activity.

Pancreatogastrostomy vs pancreatojejunostomy after pancreaticoduodenectomy: An updated meta-analysis of RCTs and our experience.

BACKGROUND: Pancreatoduodenectomy (PD) is one of the most important operations in hepatobiliary and pancreatic surgery. AIM: To evaluate the advantages and disadvantages of pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG). METHODS: This meta-analysis was performed using Review Manager 5.3. All clinical randomized controlled trials, in which patients underwent PD with pancreatico-digestive tract reconstruction via PJ or PG, were included. RESULTS: The search of PubMed, Wanfang Data, EMBASE, and the Cochrane Library provided 125 citations. After further analysis, 11 trials were included from nine counties. In all, 909 patients underwent PG and 856 underwent PJ. Meta-analysis showed that pancreatic fistula (PF) was a significantly lower morbidity in the PG group than in the PJ group (odds ratio [OR] = 0.67, 95% confidence interval [CI]: 0.53-0.86, P = 0.002); however, grades B and C PF was not significantly different between the two groups (OR = 0.61, 95%CI: 0.34-1.09, P = 0.09). Postoperative hemorrhage showed a significantly lower morbidity in the PJ group than in the PG group (OR = 1.47, 95%CI: 1.05-2.06, P = 0.03). Delayed gastric emptying was not significantly different between the two groups (OR = 1.09, 95%CI: 0.83-1.41, P = 0.54). CONCLUSION: There is no difference in the incidence of grades B and C PF between the two groups. However, postoperative bleeding is significantly higher in PG than in PJ. Binding PJ or binding PG is a safe and secure technique according to our decades of experience.

ACOX1 destabilizes p73 to suppress intrinsic apoptosis pathway and regulates sensitivity to doxorubicin in lymphoma cells.

Lymphoma is one of the most curable types of cancer. However, drug resistance is the main challenge faced in lymphoma treatment. Peroxisomal acyl-CoA oxidase 1 (ACOX1) is the rate-limiting enzyme in fatty acid ß-oxidation. Deregulation of ACOX1 has been linked to peroxisomal disorders and carcinogenesis in the liver. Currently, there is no information about the function of ACOX1 in lymphoma. In this study, we found that upregulation of ACOX1 promoted proliferation in lymphoma cells, while downregulation of ACOX1 inhibited proliferation and induced apoptosis. Additionally, overexpression of ACOX1 increased resistance to doxorubicin, while suppression of ACOX1 expression markedly potentiated doxorubicin-induced apoptosis. Interestingly, downregulation of ACOX1 promoted mitochondrial location of Bad, reduced mitochondrial membrane potential and provoked apoptosis by activating caspase-9 and caspase-3 related apoptotic pathway. Overexpression of ACOX1 alleviated doxorubicin-induced activation of caspase-9 and caspase-3 and decrease of mitochondrial membrane potential. Importantly, downregulation of ACOX1 increased p73, but not p53, expression. p73 expression was critical for apoptosis induction induced by ACOX1 downregulation. Also, overexpression of ACOX1 significantly reduced stability of p73 protein thereby reducing p73 expression. Thus, our study indicated that suppression of ACOX1 could be a novel and effective approach for treatment of lymphoma. [BMB Reports 2019; 52(9): 566-571].

ß-Asarone increases doxorubicin sensitivity by suppressing NF-κB signaling and abolishes doxorubicin-induced enrichment of stem-like population by destabilizing Bmi1.

BACKGROUND: Lymphoma is one of the most common hematologic malignancy. Drug resistance is the main obstacle faced in lymphoma treatment. Cancer stem cells are considered as the source of tumor recurrence, metastasis and drug resistance. The ß-Asarone, a low-toxicity compound from the traditional medical herb Acorus calamus, has been shown to act as an anti-cancer reagent in various cancer types. However, the anti-cancer activities of ß-Asarone in lymphoma have not been shown. METHODS: Cell counting assay was used to evaluate Raji cell proliferation. CCK8 assay was used to evaluate the cell viability. Annexin-V/PI staining and flow cytometry analysis were used to evaluate apoptosis. ALDEFLUOR assay was used to evaluate the stem-like population. Luciferase reporter assay was used to examine the activation of NF-κB signaling. Western blot and polymerase chain reaction (PCR) were used to determine the expression of interested genes. RESULTS: We showed that ß-Asarone inhibited proliferation and induced apoptosis in Raji lymphoma cells in a dose-dependent manner. Additionally, ß-Asarone functioned as a sensitizer of doxorubicin and resulted in synergistic effects on inhibition of proliferation and induction of apoptosis when combined with doxorubicin treatment. Interestingly, we found that ß-Asarone also reduced the stem-like population of Raji lymphoma cells in a dose-dependent manner, and suppressed the expression of c-Myc and Bmi1. Importantly, ß-Asarone abolished doxorubicin-induced enrichment of the stem-like population. In the mechanism study, we revealed that ß-Asarone suppressed not only basal NF-κB activity but also Tumor necrosis factor α (TNF-α) induced NF-κB activity. Moreover, blocking NF-κB signaling inactivation was critical for ß-Asarone induced apoptosis and inhibition of proliferation, but not for the effect on ß-Asarone reduced stem-like population. In fact, ß-Asarone suppressed stem-like population by destabilizing Bmi1 via a proteasome-mediated mechanism. CONCLUSIONS: Our data suggested the application of ß-Asarone to lower the toxic effect of doxorubicin and increase the sensitivity of doxorubicin in clinical treatment. More importantly, our data revealed a novel role of ß-Asarone which could be used to eliminate stem-like population in lymphoma, implying that ß-Asarone might reduce relapse and drug resistance.

SIP/CacyBP promotes autophagy by regulating levels of BRUCE/Apollon, which stimulates LC3-I degradation.

BRUCE/Apollon is a membrane-associated inhibitor of apoptosis protein that is essential for viability and has ubiquitin-conjugating activity. On initiation of apoptosis, the ubiquitin ligase Nrdp1/RNF41 promotes proteasomal degradation of BRUCE. Here we demonstrate that BRUCE together with the proteasome activator PA28γ causes proteasomal degradation of LC3-I and thus inhibits autophagy. LC3-I on the phagophore membrane is conjugated to phosphatidylethanolamine to form LC3-II, which is required for the formation of autophagosomes and selective recruitment of substrates. SIP/CacyBP is a ubiquitination-related protein that is highly expressed in neurons and various tumors. Under normal conditions, SIP inhibits the ubiquitination and degradation of BRUCE, probably by blocking the binding of Nrdp1 to BRUCE. On DNA damage by topoisomerase inhibitors, Nrdp1 causes monoubiquitination of SIP and thus promotes apoptosis. However, on starvation, SIP together with Rab8 enhances the translocation of BRUCE into the recycling endosome, formation of autophagosomes, and degradation of BRUCE by optineurin-mediated autophagy. Accordingly, deletion of SIP in cultured cells reduces the autophagic degradation of damaged mitochondria and cytosolic protein aggregates. Thus, by stimulating proteasomal degradation of LC3-I, BRUCE also inhibits autophagy. Conversely, SIP promotes autophagy by blocking BRUCE-dependent degradation of LC3-I and by enhancing autophagosome formation and autophagic destruction of BRUCE. These actions of BRUCE and SIP represent mechanisms that link the regulation of autophagy and apoptosis under different conditions.