Intrahepatic cholangiocarcinoma is a malignant tumor with an extremely poor prognosis， and its pathogenesis is complex and remains unclear. In recent years， more and more studies have focused on the role of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma. Bile-gut axis refers to the complex interaction between bile and gut microbiota， including bile salt metabolism， dynamic changes of microbiota， inflammatory response， and immune system regulation. This article elaborates on the potential mechanisms of bile-gut axis in intrahepatic cholangiocarcinoma， especially gut microbiota dysbiosis， abnormal bile salt metabolism， chronic inflammatory response， and immune system interaction， this article aims to provide new perspectives and possible therapeutic targets for future research and promote the early diagnosis and effective treatment of intrahepatic cholangiocarcinoma.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Objective To investigate the effect of serum soluble tumor necrosis factor receptor P55(sTNFR-P55)and metallothionein 1E(MT1E)on the clinical outcome of estrogen receptor(ER)positive breast cancer patients undergoing radical mastectomy.Methods The clinical data of 146 patients with ER positive breast cancer who were treated in our hospital from February 2017 to March 2018 were retrospectively analyzed.According to the clinical outcome of patients after surgery,they were divided into recurrent metastatic group and non-recurrent metastatic group.The clinical data,serum sTNFR-P55 and MT1E levels were compared between patients with recurrent metastatic group and non-recurrent metastatic group.Multivariate Logistic regression analysis was used to analyze the related factors influencing the clinical outcome of ER positive breast cancer patients undergoing radical mastectomy.The receiver operating characteristic curve(ROC)was made,and the area under the curve(AUC)was used to analyze the predictive value of serum sTNFR-P55,MT1E and their combination on the clinical outcome of ER positive breast cancer patients undergoing radical surgery.Results By the end of follow-up,32 of 146 patients with ER positive breast cancer had recurrence and metastasis.Tumor size and levels of tumor necrosis factor-α,carbohydrate antigen 125(CA125),cytokeratin 19 fragment antigen 21-1(CYFRA21-1),carcinoembryonic antigen(CEA),tumor stage Ⅲ,serum sTNFR-P55 and MT1E in the recurrent metastatic group were higher than those in the non-recurrent metastatic group(P＜0.05).Multivariate Logistic analysis showed that CYFRA21-1(OR=2.768,95％CI 1.107-6.920),CEA(OR=2.751,95％CI 1.101-6.879),tumor stage Ⅲ(OR=3.611,95％CI 1.444-9.029),sTNFR-P55(OR=3.343,95％CI 1.337-8.361)and MT1 E(OR=3.267,95％CI 1.307-8.169)were all related factors affecting the clinical outcome of ER positive breast cancer patients undergoing radical surgery(P＜0.05).ROC curve analysis results showed that the sensitivity of serum sTNFR-P55,MT1E and their combination in predicting the clinical outcome of ER positive breast cancer patients undergoing radical surgery was 78.12％(95％CI 59.56-90.06),75.00％(95％CI 56.25-87.87)and 71.88％(95％CI 53.02-85.60),respectively.The specificity was 63.16％(95％CI 53.56-71.85),75.44％(95％CI 66.32-82.80)and 96.49％(95％CI 90.73-98.87),respectively.AUC was 0.723(95％CI0.642-0.793),0.760(95％CI0.682-0.827)and 0.880(95％CI0.816-0.928)respectively.Conclusion Serum sTNFR-P55 and MT1E are related to the clinical outcome of ER positive breast cancer patients undergoing radical mastectomy,and the combination of serum sTNFR-P55 and MT1E is more effective in predicting the clinical outcome of ER positive breast cancer patients undergoing radical mastectomy.

MAGED4B belongs to the melanoma-associated antigen family; originally found in melanoma, it is expressed in various types of cancer, and is especially enriched in glioblastoma. However, the functional role and molecular mechanisms of MAGED4B in glioma are still unclear. In this study, we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue, and the level was positively correlated with glioma grade, tumor diameter, Ki-67 level, and patient age. The patients with higher levels had a worse prognosis than those with lower MAGED4B levels. In glioma cells, MAGED4B overexpression promoted proliferation, invasion, and migration, as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide. On the contrary, MAGED4B knockdown in glioma cells inhibited proliferation, invasion, and migration, as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide. MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain. The interaction between MAGED4B and tripartite motif-containing 27 (TRIM27) in glioma cells was detected by co-immunoprecipitation assay, which showed that MAGED4B was co-localized with TRIM27. In addition, MAGED4B overexpression down-regulated the TRIM27 protein level, and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine (MG132), an inhibitor of the proteasome. On the contrary, MAGED4B knockdown up-regulated the TRIM27 level. Furthermore, MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132. Accordingly, MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7 (USP7) involved in the tumor necrosis factor-alpha (TNF-α)-induced apoptotic pathway. These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1 (RIP1)-dependent TNF-α-induced apoptotic pathway, which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.
Humans ; Tumor Necrosis Factor-alpha ; DNA-Binding Proteins/metabolism* ; Ubiquitin-Specific Peptidase 7 ; Cisplatin ; Temozolomide ; Transcription Factors ; Glioma ; Cell Proliferation ; Melanoma ; Cell Line, Tumor ; Apoptosis ; Nuclear Proteins/genetics*

The adjacent anatomy of the pelvis is complicated, with digestive, urinary, reproductive and other organs as well as important blood vessels and nerves. Therefore, accurate resection of pelvic tumors and precise reconstruction of defects after resection are extremely difficult. The development of medical 3D printing technology provides new ideas for precise resection and personalized reconstruction of pelvic tumors. The “triune” application of 3D printing personalized lesion model, osteotomy guide plate and reconstruction prosthesis in pelvic tumor limb salvage reconstruction treatment has achieved good clinical results. However, the current lack of normative guidance standards such as preparation and application of 3D printing personalized lesion model, osteotomy guide plate and reconstruction prosthesis restricts its promotion and application. The formulation of this consensus provides normative guidance for 3D printing personalized pelvic tumor limb salvage reconstruction treatment.

Objective:To introduce the clinical experience and treatment effect of congenital radial longitudinal deficiency in children with one-stage bilobed flap combined with centralization by circular external fixation.Methods:Analysis and statistics from 14 children with radial longitudinal deficiency were summarized in our hospital from January 2006 to December 2018, 8 males and 6 females; aged 3 to 17 years, average 9.7 years. 3 patients on the left side, 10 patients on the right side, 1 case bilateral.1 case was type Ⅱ, 7 cases were type Ⅲ, 6 cases were type Ⅳ.2 cases were with scoliosis. The radial angulation of 30°- 90°(average 67.3°) before operation. In the first phase, bilobed flaps were used to completely release soft tissue and restore dynamic balance. After the centralization, it was fixed with a circular external fixation. Three cases underwent ulnar osteotomy and forearm extension at the same time. Follow-up indicators: Observe the flap survival in the short term, and follow up on the radial deviation of the wrist and the degree of wrist mobility for a long time.Results:In one patient, the distal part of the dorsal wrist flap was necrotic, the necrotic part was removed and directly sutured 12 days later, and the rest all survived. During a follow-up period of 2 to 8 years (average 3.6 years), the average radial angulation was 9.3° (2°to 17°), the average flexion of the wrist was 46.7°(25°to 70°), and the average extension was 14.7° (5°to 20°). One case which forearm extension had a fractured nonunion and bone graft with internal fixation was performed in 9th after surgery, and ulna healed in 3 months after bone grafting. The forearm radial deflection was significantly improved in all patients, and functional recovery was satisfactory.Conclusions:Treatment of radial longitudinal deficiency in children in one-stage bilobed flap combined with centralization by circular external fixation is an effective clinical treatment method. It can reduce the number of operations, obtain satisfactory appearance and receive good functional recovery.

Objective:To introduce the clinical experience and treatment effect of congenital radial longitudinal deficiency in children with one-stage bilobed flap combined with centralization by circular external fixation.Methods:Analysis and statistics from 14 children with radial longitudinal deficiency were summarized in our hospital from January 2006 to December 2018, 8 males and 6 females; aged 3 to 17 years, average 9.7 years. 3 patients on the left side, 10 patients on the right side, 1 case bilateral.1 case was type Ⅱ, 7 cases were type Ⅲ, 6 cases were type Ⅳ.2 cases were with scoliosis. The radial angulation of 30°- 90°(average 67.3°) before operation. In the first phase, bilobed flaps were used to completely release soft tissue and restore dynamic balance. After the centralization, it was fixed with a circular external fixation. Three cases underwent ulnar osteotomy and forearm extension at the same time. Follow-up indicators: Observe the flap survival in the short term, and follow up on the radial deviation of the wrist and the degree of wrist mobility for a long time.Results:In one patient, the distal part of the dorsal wrist flap was necrotic, the necrotic part was removed and directly sutured 12 days later, and the rest all survived. During a follow-up period of 2 to 8 years (average 3.6 years), the average radial angulation was 9.3° (2°to 17°), the average flexion of the wrist was 46.7°(25°to 70°), and the average extension was 14.7° (5°to 20°). One case which forearm extension had a fractured nonunion and bone graft with internal fixation was performed in 9th after surgery, and ulna healed in 3 months after bone grafting. The forearm radial deflection was significantly improved in all patients, and functional recovery was satisfactory.Conclusions:Treatment of radial longitudinal deficiency in children in one-stage bilobed flap combined with centralization by circular external fixation is an effective clinical treatment method. It can reduce the number of operations, obtain satisfactory appearance and receive good functional recovery.

Objective To compare the application values and setup errors between vacuum bag plus body mask and customized alpha cradle duringproton and carbon therapy using Siemens 6D robotic couch in prostate cancer patients.Methods Nineteen patients received vacuum bag plus body mask setup were allocated into the vacuum bag group andl9 patients with alpha cradle were assigned into the alpha cradle group.Orthogonal X-ray portals were performed to verify the treatment position before beam delivery in every fraction.The couch correction between the portal and reference DRR through manual image registration was recorded as setup errors in 6 directions including the lateral,supine-inferior,anterior-posterior,yaws,roll and pitch,respectively.Two-tail t-test was used to analyze the setup error data from each direction between two groups.Results In total,452 and 436 sets of data errors were collected from the vacuum bag and alpha cradle groups.The average setup errors and standard deviation in the vacuum bag and alpha cradle groups in the lateral,supine-inferior,anterior-posterior,yaws,roll and pitch directions were (0.63±0.48) cm vs.(0.33±0.24) cm (P=0.000),(0.40±0.3) cm vs.(0.31±0.25) cm (P=0.000),(0.69±0.61) cm vs.(0.82±0.69) cm (P=0.006),0.65°±0.47°vs 0.32°±0.25°(P=0.000),1.05°±0.95°vs 1.16°±0.94° (P=0.100) and 0.67°±0.56°vs 0.40°±0.36° (P=0.000),respectively.The maximum setup errors were detected in the pitch direction for both groups.Conclusions During the proton and carbon therapy using Siemens 6D robotic couch,two setup methods using vacuum bag plus body mask and customized alpha cradle should be selected according to the individual conditions of patients.A customized foot fixer should be utilized to reduce the uncertainty in the femoral head region.

Objective To reproduce a stable animal model of brain death in pigs, observe the change regularity of cerebral oxygen metabolism during the process of brain death, and to evaluate the significance and value of cerebral oxygen metabolism parameters for the diagnosis of brain death. Methods Twelve landrace pigs were used to create the brain death models using modified method of increasing epidural intracranial pressure (ICP). The mean arterial pressure (MAP) and ICP were monitored continuously during the process. The pigs were divided into four groups according to cerebral perfusion pressure (CPP) decreasing degree during brain death, namely CPP normal group and CPP decreasing 0%-30%, 30%-70%, and 70%-100% groups. Blood gas analysis of the external carotid artery and internal jugular vein were monitored discontinuously. The changes in cerebral oxygen metabolism parameters, including external carotid artery-internal jugular vein bulb oxygen content difference (AJDO2), internal jugular bulb-external carotid artery carbon dioxide partial pressure difference (DPCO2) and DPCO2/AJDO2 ratio, were observed. Results Brain death model were successfully reproduced in 12 experimental pigs. With MAP and ICP monitoring, the models at different stages of CPP could be repeatedly induced. The levels of AJDO2 and DPCO2 were increased gradually and then decreased, while the ratio of DPCO2/AJDO2 was constantly increased with the decrease of CPP. The level of AJDO2 in CPP decreasing 0%-30%group was significantly higher than that in CPP normal group [(5.86±1.21)% vs. (3.92±0.64)%], the levels of DPCO2 in CPP decreasing 0%-30% and CPP decreasing 30%-70% groups were significantly higher than those in CPP normal group [mmHg (1 mmHg = 0.133 kPa): 10.33±1.83, 11.48±2.32 vs. 6.11±1.43], and the ratios of DPCO2/AJDO2 in CPP decreasing 30%-70% and CPP decreasing 70%-100% groups were significantly higher than those in CPP normal group and CPP decreasing 0%-30% group (2.81±0.53, 4.12±1.07 vs. 1.57±0.64, 1.62±0.81). All the differences above were statistically significant (all P < 0.05). Conclusions With the decrease of CPP, cerebral oxygen metabolism showed a regular change during brain death. DPCO2 combined with DPCO2/AJDO2 is a reliable blood gas analysis index indicating intracranial hypoperfusion, which has certain reference value for the determination of brain death.

Objective To investigate the cerebral blood flow in migraine without aura with three-dimensional arterial spin labeling technology .Methods From January 2013 to February 2016, magnetic resonance perfusion imaging was operated in 20 migraine patients without aura and 20 healthy controls by using arterial spin labeling, to determine their regional cerebral blood flow (rCBF) during migraine attacks and attack-free period.The significant difference was analyzed in rCBF between the two groups .Results The rCBF was significantly lower at the headache side during migraine period ( ( 52.77 ±5.97 ) ml? 100 g-1? min-1 ) than symmetrical side in the migraine patients without aura ((62.72 ±6.65) ml? 100 g-1?min-1 , t=3.780,P<0.01).The rCBF of temporosphenoid lobe in headache side in the migraine patients without aura ((53.97 ±5.87) ml? 100 g-1? min-1) was significantly lower than corresponding region in the control group ((59.21 ±2.35) ml? 100 g-1? min-1, t=4.449, P=0.001).And no significant difference in rCBF was found in migraine patients without aura under attack-free period. Conclusions Three-dimensional arterial spin labeling could quantitatively analyze the cerebral blood flow .Monitoring the perfusion difference in migraine patients could provide some references in the pathogenesis research and therapy.