AIM:To compare the efficacy and safety of early combination therapy with ranibizumab and dexamethasone intravitreal implants versus ranibizumab monotherapy for the treatment of macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: A retrospective cohort study was conducted on a total of 62 cases(64 eyes)of patients who were first diagnosed with RVO-ME at the Eye Centre of the Affiliated Hospital of Shandong Second Medical University between February 2022 and February 2023. The subjects were divided into two groups according to the different treatment regimens: 32 cases(34 eyes)in the monotherapy group received only ranibizumab [3+pro re nata(PRN)regimen], and 30 cases(30 eyes)in the combination therapy group were injected with ranibizumab once first, followed by dexamethasone intravitreal implant 3 wk later(1+DEX regimen). The best corrected visual acuity(BCVA), central retina thickness(CRT), foveal avascular zone(FAZ)area, macular vascular density(MVD)at the level of the deep vascular complex(DVC)of the retina, the incidence of ocular adverse effects, the number of drug injections, and the total cost between the two groups were compared before and after treatment.RESULTS: At 3 wk, 3 and 6 mo, and at the final follow-up of the two groups of patients, the improvement in BCVA, CRT, and MVD in the DVC layer was significantly better than that before treatment(all P<0.05); there were differences in the comparisons of BCVA and CRT between the two groups at 6 mo and the final follow-up(all P<0.05), and the increase in the number of letters of BCVA was the most pronounced in the combination therapy group at 6 mo of treatment. Statistical significant difference was observed in the comparison of MVD in the DVC layer between the two groups at 3 and 6 mo after treatment and at the final follow-up(all P<0.05). However, no significant change in FAZ area was evident before and after treatment in both groups(P>0.05). The combination therapy group exhibited a reduced number of injections and total cost in comparison to the monotherapy group. The combination therapy group exhibited a slightly higher incidence of high intraocular pressure and cataract progression compared to the monotherapy group, with no statistical significant difference(all P>0.05). Furthermore, no serious adverse events were observed in either group following treatment.CONCLUSION:Compared with ranibizumab alone, ranibizumab combined with dexamethasone intravitreal implant significantly improved vision, reduced macular edema, and lowered the frequency of injections and total treatment cost in patients with RVO-ME. CRT and MVD in the DVC layer are reliable prognostic indicators for patients with RVO-ME.

BACKGROUND:Neuronal necroptosis induced by intracerebral hemorrhage is an important cause of secondary brain injury.Activating transcription factor 4(ATF4)is a member of the transcription activator family,which plays an important role in secondary brain injury after intracerebral hemorrhage.However,the mechanism of ATF4 in neuronal necroptosis after intracerebral hemorrhage remains unclear. OBJECTIVE:To explore the effect of ATF4 silencing(ATF4 small interfering RNA,ATF4 siRNA)on neuronal necroptosis after intracerebral hemorrhage. METHODS:The HT-22 mouse hippocampal neuron cell line and the BV-2 mouse microglial cell line were co-cultured,and hemin was used to mimic an in vitro model of intracerebral hemorrhage.A gradient concentration of hemin was used to treat cells and was set in the interval of 0-100 μmol/L,and the cell viability was evaluated by MTT assay after 24 hours of administration of hemin.The cells were divided into four groups:the blank control group without any intervention;the control group was treated with hemin(50 μmol/L),and the other two groups were treated with negative control small interfering RNA(NC siRNA)and ATF4 small interfering RNA(ATF4 siRNA)48 hours before administration of hemin.After the cells were treated with hemin(50 μmol/L)for 24 hours,PI/Hoechst staining was used to detect neuronal necroptosis.Western blot assay was used to detect the protein expression of ATF4,receptor-interacting protein 3(RIP3),and mixed lineage kinase domain-like protein(MLKL),and double immunofluorescent staining was located in neurons to observe the level of neuronal necroptosis and the regulatory effect of ATF4 on it. RESULTS AND CONCLUSION:(1)50 μmol/L of hemin could induce neuronal necroptosis to a greater extent.(2)The number of PI+/Hoechst+ cells in the control group and NC siRNA group was higher than that in the blank control group(P<0.000 1).The number of PI+/Hoechst+ cells in the ATF4 siRNA group was lower than that in the control group(P<0.000 1).(3)Compared with the control group,the ATF4 siRNA group not only inhibited the expression of ATF4 protein(P<0.001),but also inhibited the expression of RIP3 and MLKL protein(P<0.001).(4)Through double immunofluorescent staining,compared with the control group,the protein expression of RIP3 and MLKL was significantly reduced in the ATF4 siRNA group(P<0.000 1).(5)The results show that the silencing of the ATF4 gene can directly or indirectly inhibit the expression of genes related to neuronal necroptosis after intracerebral hemorrhage,and play a vital role in alleviating secondary brain injury.

Objective:To invest the risk factors associated with delayed hemorrhage after pancreaticoduodenectomy occurred.Methods:A retrospective analysis was performed from January 2012 to June 2015 Shengjing hospital 511 cases of patients who accepted pancreaticoduodenectomy.Results:The incidence of PD postoperative delayed hemorrhage was 8.81％ (45/511).Univariate analysis shows:Preoperative bilirubin levels,pancreatic fistula,biliary fistula,postoperative abdominal infection are all the meaningful related factors(P＜0.05).With the application of multivariate logistic regression analysis,pancreatic fistula (OR=2.158) and abdominal infection (OR=3.051) were independent risk factors for postoperative delayed hemorrhages (P＜0.05).Conclusion:Dealing with the postoperative complications of PD like pancreatic fistula,abdominal infection and others,early detection and rapid diagnosis and correct treatment can effectively reduce the incidence of delayed hemorrhage.

To investigate the effect of the jianpi-jiedu formula (JPJD) on the expression of angiogenesis-relevant genes in colon cancer.
 Methods: Crude extract was obtained from JPJD by water extract method. The effect of JPJD crude extract on colon cancer cell proliferation capacity was determined by MTT assays. The IC50 value was calculated by GraphPad Prism5 software. Affymetrix gene expression profiling chip was used to detect significant differences in expressions of genes after JPJD intervention, and pathway enrichment analysis was performed to analyze the differentially expressed genes. Ingenuity Pathway Analysis software was applied to analyze differentially expressed genes relevant to tumor angiogenesis based on mammalian target of rapamycin (mTOR) signaling pathway and then the network diagram was built. Western blot was used to verify the protein levels of key genes related to tumor angiogenesis.
 Results: JPJD crud extract inhibited the proliferation capacity in colon cancer cells. The IC50 values in 24, 48, and 72 hours after treatment were 13.060, 9.646 and 8.448 mg/mL, respectively. The results of chip showed that 218 genes significantly upgraded, and 252 genes significantly downgraded after JPJD treatment. Most of the genes were related to the function of biosynthesis, metabolism, cell apoptosis, antigen extraction, angiogenesis and so on. There were 12 differentially expressed angiogenesis genes. IPA software analysis showed that the JPJD downregulated expression of sphingomyelin phosphodiesterase 3 (SMPD3), VEGF, vascular endothelial growth factor A (VEGFA), integrin subunit alpha 1 (ITGA1), cathepsin B (CTSB), and cathepsin S (CTSS) genes, while upregulated expressions of GAB2 and plasminogen activator, urokinase receptor (PLAUR) genes in the colorectal cancer cell. Western blot results demonstrated that JPJD obviously downregulated expressions of phospho-mTOR (P-mTOR), signal transducer and activator of transcription 3 (STAT3), hypoxia inducible factor-1α (HIF-1α), and VEGF proteins, while obviously upregulated the level of phospho-P53 (P-P53) protein.
 Conclusion: JPJD may inhibit colorectal tumor angiogenesis through regulation of the mTOR-HIF-1α-VEGF signal pathway.
Animals ; Blotting, Western ; Cathepsin B ; drug effects ; metabolism ; Cathepsins ; drug effects ; metabolism ; Cell Line, Tumor ; drug effects ; Colorectal Neoplasms ; blood supply ; genetics ; Down-Regulation ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Profiling ; methods ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; drug effects ; metabolism ; Integrin alpha Chains ; drug effects ; metabolism ; Neovascularization, Pathologic ; genetics ; Receptors, Urokinase Plasminogen Activator ; drug effects ; metabolism ; STAT3 Transcription Factor ; drug effects ; metabolism ; Signal Transduction ; Sphingomyelin Phosphodiesterase ; drug effects ; metabolism ; TOR Serine-Threonine Kinases ; drug effects ; metabolism ; Tumor Suppressor Protein p53 ; drug effects ; metabolism ; Up-Regulation ; Vascular Endothelial Growth Factor A ; drug effects ; metabolism

Identification of complex traumatic stress disorders has beyond the traditional definition of trauma and experimentally diagnostic statement of post-traumatic stress disorder (PTSD) in Diagnostic and Statistical Manual of Mental Disorders (DSM-Ⅳ-TR). Because of the disturbance of complex trauma, traumatic stress symptoms and its hurt results, it is difficult to make accurate diagnosis and effective treatment. This article began with the reasons why it was hard to define complex trauma, viewed from clinical diagnosis and treatment, discussed the importance of defining complex trauma, its multiple effects on individuals and the psychological and social factors aggravating complex trauma.

Objective To remedy the general defects of external fixator such as poor stability,complexed operation,strong stress shielding and bad extension function. Methods A total of 102 patients with limb shaft fracture were treated with the self-made external fixation and the curative effect observed. There were 84 males and 18 females aged at 5-78 years. Of all, 76 cases had tibial and fibular fractures, 10 femoral shaft fractures (children), 4 intertrochanteric or subtrochanteric fractures, 7 ulnar or radial fractures and 5 humeral shaft fractures. Results All patients got good results through a all-course observation, among which 76 cases with tibial and fibular fractures were followed up for 3 months to one year. Furthermore, the mean substantial bone healing time was only 3.5 months. The joint functions of the knee and the ankle recovered synchronously, with an overall excellence rate of 93.4%. No displacement of the fractured part or further fracture occurred. Conclusions The structure and function of the self-made external fixation accord with the demanding of current external fixator in orthopaedics.