This article systematically reviews the role and relationship of heme oxygenase （HO） in the pathogenesis of metabolic associated fatty liver disease （MAFLD） and discusses the biological function of HO， its expression in the liver， its association with lipid metabolism， and its regulatory role in inflammatory reaction and oxidative stress， in order to reveal the potential therapeutic targets and mechanism of HO in MAFLD and provide new perspectives and directions for future treatment strategies.

Objective:To verify and calibrate the CT modeling curves of three CT devices in RayStation proton treatment planning system (TPS).Methods:CT-mass density (CT-MD) curves were established by CT Hounsfield units of different tissue substitute materials obtained by scanning the model with CT equipment. CT-stopping power (CT-SP) curves were established by calculation based on the chemical composition of various human tissues. The equivalent water thickness of tissue substitute modules was calculated with different CT modeling curves in TPS. The actual equivalent water thickness of various modules was measured by a Bragg peak detector, and compared with the calculated values of TPS to verify the accuracy of different CT models.Results:The differences of CT modeling curves were significantly different under different tube voltage scanning protocols. Compared with CT-MD curves, CT-SP curves based on the stoichiometric calibration were more suitable for proton dose calculation. However, the values of stopping power corresponding to high CT values still needed to be optimized, and the calculation error after calibration was less than 3%.Conclusion:The method of verifying and calibrating CT unit curves of proton TPS is described, proving that the CT-SP curves after stoichiometric calculation are more suitable for proton dose calculation.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Objective:To investigate the effect and mechanism of circular RNA (cirRNA) on the radiosensitivity of rectal cancer.Methods:The differential circRNAs in radiosensitive and radioresistant rectal cancer tissues (biopsy tissue before radiotherapy and chemotherapy) were detected by gene sequencing, and the effect of circRNAs on the radiosensitivity of colorectal cancer cells was further confirmed in vitro. Results:Through gene sequencing of rectal cancer tissue samples, 64 circRNAs were found to be highly expressed in radiosensitive rectal cancer tissues, and 36 circRNAs were lowly expressed in radiosensitive tissues. Ten differential circRNAs were selected and verified by qRT-PCR, and it was found that circATL2 was highly expressed in radiosensitive rectal cancer tissues. In vitro cell experiment indicated that up-regulation of circATL2 expression could significantly improve the radiosensitivity of rectal cancer. Subsequently, 8 miRNAs lowly expressed in radiosensitive rectal cancer tissues were analyzed. The direct binding relationship between miR-205 and circATL2 was confirmed by dual luciferase reporter assay. The rescue experiment confirmed that circATL2 in rectal cancer regulated the radiosensitivity of rectal cancer through miR-205. Conclusion:circATL2 regulates the radiosensitivity of rectal cancer by binding to miR-205.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

Objective To investigate the imaging anatomy and clinical significance of the inferior pancreaticoduodenal veins (IPDVs).Methods The retrospective and descriptive study was conducted.The clinicopathological data of 42 patients with pancreatic head ductal adenocarcinoma who were admitted to Peking Union Medical College Hospital from January to June 2018 were collected.There were 24 males and 18 females,aged from 41 to 78 years,with an average age of 61 years.Patients received preoperative contrast-enhanced computed tomography (CT) examination with 1 mm slice thickness,and underwent corresponding surgery according to the preoperative evaluation.Observation indicators:(1) results of preoperative CT examination;(2) surgical situations.Normality of measurement data was analyzed using Shapiro-Wilk test.Measurement data with skewed distribution were described as M (QR) or M (range),and comparison between groups was analyzed by the Mann-Whitney U test.Count data were described as absolute number or percentage,and comparison between groups was analyzed by the chi-square test.Results (1) Results of preoperative CT examination:42 patients received preoperative contrast-enhanced CT examination with 1 mm slice thickness.① The first jejunal venous trunk was identified in all the 42 patients.The first jejunal venous trunk crossed dorsal to the superior mesenteric artery (SMA) in 34 patients and ventral to the SMA in 8 patients.② Of 42 patients,2 showed no IPDV,and 40 showed IPDV including 23 with 1 IPDV,13 with 2 IPDVs,3 with 3 IPDVs,and 1 with 4 IPDVs.A total of 62 IPDVs were identified in the 42 patients,with an average IPDV number of 1 (range,0-4).There were 43 IPDVs drained into first or second jejunal venous trunks and 19 IPDVs drained into superior mesenteric vein (SMV).③ Of 42 patients,type Ⅰ IPDV was identified in 32 patients including 20 with 1 IPDV drained into jejunal venous trunk at dorsal side of SMA,7 with 2 IPDVs drained into jejunal venous trunk at dorsal side of SMA,2 with 3 IPDVs drained into jejunal venous trunk at dorsal side of SMA,and 3 with 1 IPDV drained into jejunal venous trunk at ventral side of SMA,and non-type Ⅰ IPDV was identified in 10 patients;type Ⅱ IPDV was identified in 18 patients including 17 with 1 IPDV drained into SMV and 1 with 2 IPDVs drained into SMV,and non-type Ⅱ IPDV was identified in 24 patients.Some patients can simultaneously had type Ⅰ and type Ⅱ IPDV.(2) Surgical situations:42 patients underwent pancreatoduodenectomy,14 of which underwent laparoscopic surgery and 28 underwent open surgery.There were 5 cases with SMV or portal vein reconstruction,and 18 with intraoperative blood transfusion.All the 42 patients were diagnosed as pancreatic ductal adenocarcinoma by postoperative pathological examination,including 30 of R0 resection and 12 of R1 resection.The volume of intraoperative blood loss,cases with intraoperative blood transfusion,cases with R0 and R1 resection (situation of surgical margin),cases with SMV or portal vein reconstruction were 650 mL(853 mL),15,20,12,4 in the 32 patients with type Ⅰ IPDV,aod 475 mL (480 mL),3,10,0,1 in the 10 patients with non-type Ⅰ IPDV;there were significant differences in the volume of intraoperative blood loss and situation of surgical margin (Z=94.000,x2=5.250,P＜ 0.05).There was no significant difference in the cases with intraoperative blood transfusion,cases with SMV or portal vein reconstruction between patients with type Ⅰ and non-type Ⅰ IPDV (x2 =0.045,0.886,P＞0.05).Conclusions IPDVs can be distinguished on the contrast-enhanced CT with slice thickness,and classified as IPDVs drained into SMV or jejunal venous trunk.It is necessary to carefully deal with IPDVs drained into jejunal venous trunk in the pancreaticoduodenectomy due to its more volume of intraoperative blood loss and lower R0 resection rate.

[Abstract] EGFRvIII (epidermal growth factor receptor variant Ⅲ) is the most common mutant of epidermal growth factor receptor, which expresses in over 30% glioblastoma multiforme (GBM). EGFRvIII results from deletion of exon 2-7, leading to its constitutive activation, which is closely related to tumorigenesis, development and poor prognosis of GBM. The unique glycine site on EGFRvIII provides ideal molecular target for immunotherapy, which possess great potential value of killing GBM cell, inhibiting progress and invasion. Encouraging progress has been achieved in peptide/DC vaccine, therapeutic antibody, small molecular inhibitor and adoptive immunotherapy experimentally and clinically. The characteristics of EGFRvIII and the development in its oriented immunotherapy were summarized in this review.

In order to study the relationship between Staphylococcal nuclease(SNase) and diabetes mellitus,genetic engineering bacteria E.coli BL21/pET28a-His-SNase was constructed,the expression of soluble extracellular protein SNase was induced and the a preliminary research was made on it.An expression vector pET28a-His-SNase plasmid containing the His-SNase gene was constructed and transformed into E.coli BL21 (DE3) competent cells.The protein was induced by lactose and purified by ultrasound destruction and Ni-affinity chromatography,respectively.It was then analyzed by SDS-PAGE and Western blot.The enzymatic properties for SNase has been preliminary studied as well.Results indicated that the purity of the correctly expressed fusion protein HisSNase was over 85％.SNase showed good activity within a wide range of pH and good heat resistance.This experiment might be a foundation work for the further study on the relationship between SNase and with diabetes.

Objective: To discuss the impact of updated definition and classification system of pancreatic fistula published in 2016 on the postoperative classification of pancreatic fistula. Methods: Retrospective analysis was made on patients who underwent pancreatic surgery at ward 1 in Department of General Surgery, Peking Union Medical College Hospital from January 2015 to December 2016.A total of 408 patients were included in this retrospective study, male/female was 184/224, aged from 9 to 81 years with mean age of 51.6 years.One hundred and fifty-two cases were performed pancreaticoduodenectomy, 125 cases for distal pancreatectomy, 43 cases for spleen preservation distal pancreatectomy, 61 cases for partital pancreatectomy or enucleation, 8 cases for middle pancreatectomy, 6 cases for pancreaticojejunostomy and 13 cases for other procedures.Clinical data including postoperative drainage fluid volume, amylase concentration, duration of hospitalization and drainage were obtained, revaluated and re-analyzed, classified grounded on 2005 edition and 2016 edition, respectively.t-test was adopted for data analysis. Results: According to the previous standards, the incident rate of pancreatic fistula was 57.4%, and the incident rate of B-level plus C-level pancreatic fistula was 35.8%, which decreased to 13.7% based on 2016 edition.Nine patients who received percutaneous puncture or endoscopic drainage was regraded from C-level to B-level. The average duration of postoperative hospitalization of patients without pancreatic fistula was (12.5±6.0)days, demonstrating no significant difference compared to (14.1±7.7)days, duration of postoperative hospitalization of A-level(under 2005 edition of criteria) pancreatic fistula group(t=1.66, P=0.09) and (12.4±6.1)days, duration of postoperative hospitalization of biochemical leakage group(t=0.14, P=0.89). Nevertheless, there was statistical significant difference between the average postoperative duration of hospitalization(30.7±16.9) days of B-level(under 2016 criteria) pancreatic fistula patients and pancreatic fistula-free patients as well as the biochemical leakage group patients (t=7.10, 7.13; both P<0.01). Conclusions Based on the new diagnostic criteria, the incidence of postoperative pancreatic fistula decreased dramatically.New classification system downgraded part of cases graded C-level pancreatic fistula to B-level and some B-level to biochemical fistula.The new diagnostic classification and criteria facilitated clinical practice, accomplished better conformity to clinical reality and potentially enacted clinical outcome.