Objective:To investigate the efficacy and safety of different transcatheter arterial chemoembolization(TACE)-based regimens in patients with unresectable hepatocellular carcinoma(uHCC)and explore the optimal timing for combining TACE with tyrosine kinase inhibit-ors(TKIs)and immune checkpoint inhibitors(ICIs).Methods:A retrospective analysis was conducted on data from 555 patients with uHCC who underwent TACE-based treatment between April 2016 and December 2021 in Nanfang Hospital,Southern Medical University.The pa-tients were assigned into the following four groups according to different treatment regimens:TACE group(n=317),TACE combined with TKIs group(TACE+TKIs,n=66),TACE combined with ICIs group(TACE+ICIs,n=33),and TACE combined with TKIs+ICIs group(TACE+TKIs+ICIs,n=139).Subgroup analysis was performed within the TACE+TKIs+ICIs group,with patients being assigned into"pre-TACE"and"post-TACE"groups based on the timing of the combination therapy.Univariate and multivariate Cox regression analyses were conducted to identify pro-gnostic factors influencing overall survival(OS).Results:The TACE+TKIs+ICIs group showed the longest OS(21.9 months,95%confidence in-terval[CI]:17.2-26.6,P=0.030)and progression-free survival(PFS)(8.3 months,95%CI:7.3-9.3,P=0.004)compared to those in the other three groups.In the subgroup analysis,the"post-TACE"group had longer OS than the"pre-TACE"group(26.8 months vs.19.2 months,P = 0.011).The objective response rate(ORR)was 32.8%,41.1%,42.4%,and 52.5%(P=0.001)and the disease control rate(DCR)was 59.6%,71.2%,69.7%,and 82.7%(P<0.001)in the TACE,TACE+TKIs,TACE+ICIs,and TACE+TKIs+ICIs groups,respectively.The adverse events were similar to those reported in previous studies.Cox regression analysis revealed that tumor number,extrahepatic metastasis,and treatment regimen were independent factors influencing OS in patients(all P<0.05).Conclusions:TKIs or ICIs can improve OS and PFS in patients with uHCC receiving TACE,and the combination of TKIs+ICIs with TACE achieves better beneficial outcomes.The greatest OS was observed when the combination therapy TKIs+ICIs was initiated within 3 months after the first TACE procedure.

Objective:To explore the value of monocyte subsets and CD64 expression in the diagnosis and prognosis of sepsis.Methods:A prospective case-control study was designed. 30 septic patients and 30 non-septic patients who were admitted to the intensive care unit (ICU) of the PLA Army Characteristic Medical Center from March 2021 to March 2022 were enrolled. After 1, 3, and 5 days of ICU admission, peripheral blood samples were taken from patients. Flow cytometry was used to detect the proportion of monocyte subsets and the expression level of CD64 on the surface, and the difference of expression between patients in two group was analyzed. The risk variables for sepsis were analyzed using single-factor and multi-factor Logistic regression. The diagnostic efficacy of each risk factor for sepsis was determined using the receiver operator characteristic curve (ROC curve).Results:One day after ICU admission, the proportions of monocytes and classic monocytes in white blood cells (WBC) of septic patients were significantly lower than those of non-septic patients [proportion of monocytes to WBC: (4.13±2.03)% vs. (6.53±3.90)%, proportion of classic monocytes to WBC: 1.97 (1.43, 2.83)% vs. 3.37 (1.71, 5.98)%, both P < 0.05]. The proportion of non-classical monocytes in monocytes was significantly higher in septic patients than that in non-septic patients [(11.42±9.19)% vs. (6.57±4.23)%, P < 0.05]. The levels of CD64 expression in monocytes, classic monocytes, intermediate monocytes and non-classic monocytes were significantly higher in sepsis patients than those in non-septic patients [mean fluorescence intensity (MFI): 13.10±6.01 vs. 9.84±2.83 for monocytes, 13.58±5.98 vs. 10.03±2.84 for classic monocytes, 13.48±6.35 vs. 10.22±2.99 for intermediate monocytes, 8.21±5.52 vs. 5.79±2.67 for non-classic monocytes, all P < 0.05]. Multivariate Logistic regression research showed that CD64 in typical monocytes [odds ratio ( OR) = 1.299, 95% confidence interval (95% CI) was 1.027-1.471, P = 0.025] and the proportion of non-typical monocytes in monocytes ( OR = 1.348, 95% CI was 1.034-1.758, P = 0.027) were the independent risk factors for sepsis. ROC curve showed that the area under the ROC curve (AUC) of CD64 expression of classical monocytes, the fraction of non-classical monocytes in monocytes, and procalcitonin (PCT) in the diagnosis of sepsis was 0.871. A correlation analysis revealed a negative relationship between the acute physiology and chronic health status evaluation Ⅱ (APACHE Ⅱ) on the first, third, and fifth days following ICU admission and the expression level of CD64 in patients' classic monocytes ( r values were -0.264, -0.428 and -0.368, respectively, all P < 0.05). Conclusions:Combining the proportion of non-classical monocytes in monocytes, the level of plasma PCT, and the CD64 expression of classic monocytes in peripheral blood has good efficacy in identifying sepsis and assessing its severity.

Objective:To investigate the function of miR-5581-5p and its interaction with tripartite motif 22 (TRIM22) during the terminal differentiation of human acute promyelocytic leukemia (APL) cells into granulocytes.Methods:APL cells (NB4) were differentiated into granulocytes by all-trans retinoic acid (ATRA), using dimethylsulfoxide (DMSO) as the control. The expression of TRIM22 was detected by real-time fluorescent quantitative PCR (qRT-PCR) and Western blotting, and the expression of miR-5581-5p was detected by qRT-PCR during cell differentiation. miRNA expression was regulated by cell transfection with miR-5581-5p mimic and inhibitor, and negative control was set, and qRT-PCR was used to verify the regulatory effect. Luciferase binding assay was performed to detect the presence of targeted binding. Western blotting was used to detect the expression of TRIM22 after miRNA differential expression. Flow cytometry was used to detect the effects of the regulation of miR-5581-5p on the differentiation of NB4 cells induced by ATRA.Results:After ATRA induced NB4 cells to differentiate into granulocytes, the gene expression level of TRIM22 was significantly higher than that of the control group (24.56±2.80 vs. 1.02±0.13; t=8.392, P=0.001). The level of protein expression was also significantly higher than that of the control group (0.80±0.01 vs. 0.17±0.01; t=44.900, P<0.001). The expression level of miR-5581-5p in NB4 cells differentiation group was significantly lower than that in the control group (0.14±0.02 vs. 1.01±0.08; t=10.840, P<0.001). The results of the dual luciferase reporter gene showed that the luciferase activity of the co-transfected miR-5581-5p mimic and TRIM22 WT group was significantly lower than that of the co-transfected miR-5581-5p mimic and TRIM22 MUT group (0.73±0.02 vs. 0.98±0.03; t=7.534, P=0.002). Western blotting showed that after transfection with miR-5581-5p inhibitor, the expression of TRIM22 was significantly higher than that of the negative control (0.44±0.01 vs. 0.21±0.01; t=18.290, P<0.001). While after transfection with miR-5581-5p mimic, the expression of TRIM22 decreased significantly compared with the negative control (0.62±0.01 vs. 0.80±0.02; t=6.402, P=0.003). CD11b expression of miR-5581-5p mimic group after ATRA treatment was significantly lower than that of the control group (45.80±1.80 vs. 56.61±1.88; t=4.159, P=0.014). The expression of CD11b in miR-5581-5p inhibitor group was significantly higher than that in the control group (66.48±2.54 vs. 52.60±1.70; t=4.539, P=0.011). Conclusion:miRNA-5581-5p can bind to TRIM22 3′UTR and negatively regulate TRIM22 expression. The decrease of miR-5581-5p can increase the expression of TRIM22, then promote the differentiation of ATRA-induced NB4 cells into granulocytes.

A 25-year-old man with extensive burn due to industrial dust explosion was admitted to the First Affiliated Hospital of Naval Medical University on 16th October, 2018. Four days after the first skin grafting and vacuum sealing drainage surgery, the patient developed signs of uncontrolled severe inflammation and shock. However, several atypical manifestations interfered the diagnosis of septic shock. After giving emergency treatment including fluid resuscitation, broad-spectrum antibiotics, and administration of vasopressor agents, the patient′s condition was alleviated, but quickly relapsed and deteriorated, with acute pulmonary edema appeared in the evening of the same day. Finally, the condition was reversed by completely removing the negative pressure devices on upper limbs and thorough dressing change. This case suggests that the diagnosis and treatment of infection in patients with extensive burn need comprehensive analysis. Timely intervention of the wound is the key to control the exacerbation of sepsis. In addition, the possibility of pulmonary edema in patients with sepsis should be on high alert.

Objective To summarize the therapeutic experience of lower limb pain syndrome caused by tacrolimus (FK506) after liver transplantation. Methods A 52-year-old male patient diagnosed with virus B hepatitis (hepatitis B), post-hepatitis liver cirrhosis at the decompensation stage and malignant liver tumors developed bilateral lower limbs pain syndrome after liver transplantation with FK506 immunosuppressant. After eliminating the possibility of angioneurotic pain, FK506 was terminated and replaced by sirolimus (SRL) therapy. The blood concentration was maintained at 6~8 ng/mLduring the early stage, and then gradually adjusted according to the survival time of the liver graft. Results After 2-weeks conversion therapy, the swelling and pain of bilateral lower limbs of the patient were gradually relieved, and the skin pruritus was gradually healed. After 1 month, the patient was basically restored to normal activity and function. No recurrence was reported until the submission date of this manuscript. Conclusions Bilateral lower limbs pain syndrome caused by adverse reaction of FK506 is relatively rare. FK506 can be substituted by SRL to avoid the adverse reaction.

Objective: To investigate the safety and efficacy of haploidentical hematopoietic stem cell transplantation with different intensity conditioning regimen in the treatment of childhood aplastic anemia (AA) . Methods: Thirty-seven AA patients who underwent haploidentical transplantation in BaYi Children's Hospital Affiliated to PLA Army General Hospital from January 2013 to January 2017 were enrolled. According to the dosage of conditioning regimen, 34 patients excluding 3 other conditioning regimens were divided into high-dosage group (regimen 2, 22 cases) and low-dosage group (regimen 3, 12 cases). The data of Engraftment, graft-vs-host disease (GVHD), hematopoietic reconstitution, relapse, infection, overall survival (OS) were analyzed. The comparison between the two groups was tested by χ² test. Results: A total of 35 of 37 patients achieved primary engraftment; 2 cases died of regimen-related toxicity and severe infection before the infusing of the grafts. The activation rate of CMV and EBV was 60% (21/35) . Post-transplant lymphocyte disease (PTLD) of lung occurred in one case. The cumulative incidences of acute GVHD grade Ⅰ-Ⅳ and chronic GVHD were 29% (10/35) and 34% (12/35) respectively and the incidence of extensive chronic GVHD was 6% (2/35) . The median follow-up time was 18.8 (2.9-44.1) months, the OS was 92% (34/37) .All survived patients were no longer dependent on blood transfusion and none of them had recurrence. Comparing the rates of overall survival(86%(19/22) vs.100%(12/12)) and rates of chronic GVHD(40%(8/20) vs. 17%(2/12)) in regimen 2 and regimen 3 group, there were no significant difference (χ²=1.742, 1.841, all P>0.05) . Significant difference was found at the incidence of Ⅰ-Ⅳ acute GVHD (10% (2/20) vs. 50% (6/12) ,χ²=6.200, P=0.013). Conclusions Haploidentical hematopoietic stem cell transplantation is effective and safe. It is suitable for patients who are not eligible for matched donor transplantation. Application of reduced dose preconditioning in haploid transplantation is worth exploring.

Objective To explore the clinical significance of CT three-dimensional reconstruction visualization system for surgical planning and intraoperative guidance for primary liver cancer (PLC).Methods Clinical data of 46 patients with PLC admitted to Chinese PLA General Hospital from March 2016 to March 2017 were retrospectively analyzed.The informed consents of all patients were obtained and the local ethical committee approval was received.All patients were divided into the visualization (n=23)and control groups (n=23).In visualization group,18 patients were male and 5 were female with an average age of (61±9) years.In control group,16 cases were male and 7 were female,aged (60±9) years on average.All patients were diagnosed with liver cancer before operation.In visualization group,CT 3D reconstruction visualization system was used for accessing the condition of patients before operation.The surgical procedure,operation time,intraoperative blood loss and postoperative complications of two groups were observed.The operation time and intraoperative blood loss were compare by t test.The rate comparison was conducted by Chi-square test.Correlation analysis was performed by Pearson correlation analysis.Results 3D reconstruction visualization system could precisely display the relationship between tumors and vasculature and identify the anatomical variations.In visualization group,the percentage of undergoing minimally invasive surgery was 48％ (11/23),significantly higher than 17％ (4/23) in control group (x2=4.85,P＜0.05).In visualization group,the intraoperative operation time,blood loss and length of hospital stay were (128±38) min,(135±67) ml and (7.7±2.3) d,significantly less than (205±56) min,(270±83) ml and (10.9±2.0) d in control group (t=-5.37,-3.31,-4.92;P＜0.05).The postoperative levels of ALT and TB in visualization group were (205±96) U/L and (12.2±2.4) μmol/L,significantly lower than (302±136) U/L and (18.5±3.8) μmol/L in the control group (t=-2.81,-6.67;P＜0.05).In visualization group,the estimated volume of resected liver before operation was (483±30) ml,where no significant difference was observed compared with the actual intraoperative resected liver volume (437±30) ml (t=1.13,P＞0.05),and a positive correlation was observed between them (r=0.814,P＜0.05).Conclusions CT 3D reconstruction visualization system is useful for preoperative safety assessment,locating the key anatomical parts,optimizing surgical plans so as to conduct the precise hepatectomy.

Objective To investigate the effect of regulatory dendritic cells treated by extracorporeal photochemotherapy on T cell proliferation. Methods Human peripheral blood mononuclear cells (PBMCs) were obtained and the immature dendritic cells (imDCs) were induced by recombinant human granulocyte and macrophage colony stimulating factors. SPDCs were obtained by PUVA treatment, and ECDCs were co-cultured with imDCs and PUVA-SP to obtain immunoprecipitated dendritic cells. In vitro, imDCs were co-cultured with SPDCs to obtain SPDCs; imDCs were added to 10ng/ml of LPS, and cultured for 1 day to obtain DCs. The expressions of CD11c, CD83 and CD86 on the surface of the cells were detected. The effect of imDCs on the proliferation of recipient T cells was detected by mixed lymphocyte culture method. Results The early apoptosis rate of PUVA-treated cells was 91.33%. The positive expression rates of CD83 and CD86 in ecpDCs were 22.83%±5.26% and 22.06%±4.37%, respectively, which were similar to those of imDCs (15.06%±0.59%, 15.19%±1.83% (P<0.01), but significantly lower than those in DCs (99.79%±0.36%, 99.85%±0.19%, respectively), the difference was statistically significant (P<0.01). The recipient imDC cells phagocyting the appoptotic splenic lymphocytes from the donor significantly inhibited the proliferation of recipient T cells. Conclusion Apoptosis of splenic lymphocytes induced by extracorporeal photochemotherapy can inhibit the maturation of dendritic cells and inhibit the proliferation of T lymphocytes.

Objective To investigate the lens and pituitary dose impacted by additional filtration and collection field in head and neck DSA examinations. Methods All images were acquired by a Philips ALLura Xper FD 20 DSA machine. The combination of the different collection fields (48 cm, 42 cm, 31 cm, 22 cm) and additional filtrations (0.9 mmCu+1.0 mmAl, 0.4 mmCu+1.0 mmAl, 0.1 mmCu+1.0 mmAl) were adjusted when the anthropomorphic phantom filled with dosimeter was scanned in anterioposterior and lateral positions with 2D?DSA and 3D?DSA. The dose area product (DAP), air kerma (AK) and the radiation dose values of bilateral lens and pituitary were measured and recorded. The 2D and 3D?DSA regional absorption dose on lens and pituitary were analyzed using t' test, the correlations between DAP and AK parameters and different regional absorption doses were evaluated by Pearson rank correlation coefficient. Results Absorption doses of left lens, right lens and pituitary with 2D?DSA (n=12) were as following:(2.77 ± 0.68), (6.23 ± 3.54), (8.65 ± 2.62) mGy, while the parameters with 3D?DSA (n=12) were (1.78 ± 0.82), (2.18±1.15), (3.32±0.64) mGy, respectively;the results revealed a significant difference (t'=3.20, 3.76 and 6.85, P<0.01). DAP [(8 739±5 731) mGy·cm2] had a relationship with absorption dose of pituitary, left lens and right lens [(5.988 ± 3.299),( 2.258 ± 0.872),( 4.207 ± 3.303) mGy, r values were 0.766, 0.684, 0.727; P<0.01]. AK values was (31 ± 23) mGy and it had a relationship with pituitary absorption dose (r value was 0.894, P<0.01). The lens dose was reduced when the additional filtration was increased and the collection field was decreased, the radiation dose of the pituitary was reduced when both the additional filtration and the collection field were increased. Conclusions In the head and neck DSA examinations, the radiation dose of the lens and the pituitary had different changes with the different additional filters and collecting fields. The organ dose with 3D?DSA was significantly less than that with 2D?DSA.

Objective To analyze the correlation of tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC)with the expression levels of regulatory T cell (Treg)and cytokines in peripheral blood. Methods A total of 56 patients who underwent liver transplantation in the 309th Hospital of People's Liberation Army from 2010 to 2014 were studied. According to the postoperative pathological data,all the patients were divided into the group of liver transplantation for HCC (HCC group,n=28)and group of liver transplantation for cirrhosis (liver cirrhosis group,n=28), of which the HCC group was further divided into non-recurrence group (n=8)and recurrence group (n=20)according to the situation of postoperative tumor recurrence. The expression levels of Treg and cytokines [vascular endothelial growth factor (VEGF),interleukin (IL)-2,IL-10,IL-12,transformation growth factor (TGF)-βand interferon (IFN)-γ]in peripheral blood of the patients in various groups were compared. Results Compared with the liver cirrhosis group,levels of IFN-γand IL-12 in the non-recurrence group increased significantly (both P<0.05);levels of Treg%,VEGF,IFN-γ, IL-10 and TGF-βin the recurrence group increased significantly,while levels of IL-2 and IL-12 decreased significantly (all P<0.05). Compared with the non-recurrence group,levels of Treg%,VEGF,IL-10 and TGF-βin the recurrence group increased significantly,while levels of IFN-γ,IL-2 and IL-12 decreased significantly (all P<0.05 ). Conclusions Levels of Treg and cytokines can be used to predict the tumor recurrence after liver transplantation for HCC.