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This study was to explore the effect and mechanism of Let-7b nanocomposite on the expression of inflammatory factors in the cerebrospinal fluid (CSF) of purulent meningitis. 45 patients with purulent meningitis (PM) were selected as observation group (group A), and 38 patients with normal CSF without central nervous system diseases were selected as the control group (group B). The CSF of the two groups were collected to detect the inflammatory factors interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-1α), matrix metalloproteinase 9 (MMP9), interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), and Let-7b level with the double antibody sandwich enzyme-linked immunosorbent assay (ELISA). The Let-7b nanocomposite was prepared, and its morphology, particle size, and Zeta potential were analyzed. In addition, the degradation kinetics, cytotoxicity, and phagocytic efficiency (PE) of Let-7b nanocapsules were detected. 36 healthy adult New Zealand (NZL) rabbits were randomly grouped into a control group (group C) (0.9% normal saline (NS)), a model group (Escherichia coli (E. coli) modeling, group D), and a test group (E. coli modeling + Let-7b nanocapsules, group E), with 12 rabbits in each group. The changes of inflammatory factors in CSF of the three groups were detected and compared. It was found that the expression levels of IL-8 and IL-1 β in the group A were much higher than those in the group B (P < 0.01), and the MMP9 and TNF-α levels in the group B were much lower in contrast to the group A (P < 0.001). The expression of Let-7b in the group A was lower obviously in contrast to the group B (P < 0.001). Let-7b nanocapsules were irregularly spherical, with an average particle size (APS) of 23.1 nm, a polydispersity index (PDI) of 0.232, and the Zeta potential of around +15 mV. Let-7b nanocapsules showed obvious polymer shell absorption peaks at 1,015 cm-1, 1,228 cm-1, and 1,547 cm-1. The IL-8 and IL-1β levels of the group D were greatly different from those in the other two groups (P < 0.01). The levels of TNF-α and MMP9 in the group D were greatly different in contrast to the group C (P < 0.001) and the group E (P < 0.01). It indicated that Let-7b nanocomposite could lower the expression levels of IL-8, IL-1β, MMP9, and TNF-α in the CSF of patients with purulent meningitis dramatically, which provides a reliable basis for immunotherapy of purulent meningitis with Let-7b.

The IDEAL framework allowed safe introduction of salvage liver resection after LEN-TAP strategy in an evidence-based manner without exposing the initial patients to unacceptable risk. The findings showed that LEN-TAP conversion strategy is feasible with manageable AEs for uHCC, and salvage liver resection is safe and beneficial.

BACKGROUND: To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) with (131)iodine-doxorubicin-eluting gelatin microspheres ((131)I-DEM TACE) compared with conventional TACE (cTACE) with polyvinyl alcohol foam (PVA) embolization microspheres. METHODS: A total of 22 patients diagnosed with hepatocellular carcinoma were equally divided into 2 groups. The patients who underwent TACE with (131)I-DEM (25.7×10(7) Bq of 131iodine and 10 mg of doxorubicin) were compared to controls who received cTACE with PVA embolization microspheres. Therapeutic effects were evaluated by the tumor regression rates, levels of alpha-fetoprotein in serum, survival rates, and complications. RESULTS: The operative complications of the 2 groups were not significantly different (P=0.753). The radioactivity ratio of the tumor to the liver was approximately 4.1:1 for the (131)I-DEM TACE group. In the (131)I-DEM TACE group, 54.5% of patients achieved tumor regression of more than 50%, compared to 36.6% of patients in the cTACE group. AFP levels in serum declined in 100% of patients in the (131)I-DEM TACE group and 50% of patients in the cTACE group. The median survival time of the patients was 12.0±3.3 months for the (131)I-DEM TACE group and 10.0±3.3 months for the cTACE group. There were no significant differences in survival between the 2 groups (P=0.414). CONCLUSIONS: (131)I-DEM may become a potential radiochemoembolization agent to treat patients with unresectable hepatocellular carcinoma through TACE.

453 Background: More than 70% of hepatocellular carcinoma (HCC) patients are in the intermediate or advanced stages at the time of diagnosis. TACE, TKI and PD-1 antibody are all recommended for patients with unresectable HCC (uHCC) according to Chinese HCC guidelines. There are few scientific trials to back up the safety and effecacy of TACE+TKI+PD-1 antibody for the treatment of uHCC and conversion resection. In this study, we explored the safety and efficacy of the TACE+TKI+PD-1 antibody in uHCC. Methods: This is a prospective, multicenter, cohort study (NCT04997850). Key Eligibility Criteria:18 years old ≤ age ≤ 70 years old; HCC confirmed by histopathology or cytology; No systemic treatment history. ECOG PS score 0-1; Child-Pugh A/B; BCLC stage B/C.Experience group: TACE + Lenvatinib (12mg when≥ 60kg/8mg when < 60kg QD) + Camrelizumab/ Sintilimab (200 mg ivgtt Q3W);Control group: TACE. Results: From Sep 2020 to May 2021, 38 patients were enrolled in experimental group (Table). At the cutoff date (Sep 10 2021), the median follow-up was of 33.34 weeks (Table). The conversion resection rate was 50% (19/38), and the conversion success rate was 52.6% (20/38). Among the 19 patients, 5 cases achieved complete pathological response and 1 case achieved major pathological response. The 48 weeks’ OS rate and PFS were 96.4% (95%CI 92.9% to 99.9%) and 91.7%(95%CI 85.8% to 97.4%).22 patients had level 3 treatment related adverse events (TRAE), there were no level 4 and 5 TRAEs. At the last follow-up, the ORR rate based on mRECIST was 84.2%, and the DCR rate was 94.7% (Table). Conclusions: TACE + Lenvatinib + PD-1 antibody is safe and effective, and conversion resection after the triple-treatment is feasible for uHCC. Clinical trial information: 04997850.[Table: see text]

BACKGROUND Parkinson's disease (PD) is a movement disorder. microRNA (miR)-133 expression is reduced in PD patients and in mice with a dopamine neuron deficiency. We aimed to identify the mechanism of miR-133a in apoptosis and autophagy in PD. MATERIAL AND METHODS The optimal concentration of MPP⁺ (1-methyl-4-phenylpyridinium ion) was initially determined to construct a PD cell model. Gain-of function experiments were carried out to evaluate the role of miR-133a in PD. The levels of miR-133a, RAC1 (Ras-related C3 botulinum toxin substrate 1), apoptosis-related factors, and autophagy-related factors were detected after detection of cell proliferation, cell cycle, and apoptosis. Transmission electron microscopy was applied to observe autophagosomes, and immunofluorescence staining was performed to detect LC3 and further analyze the effect of miR-133a on autophagy in a PD cell model. RESULTS Low miR-133a expression was detected in a cell model of MPP⁺-induced PD. After overexpressing miR-133a, cell proliferation increased, and apoptosis (cleaved caspase-3 and Bax levels decreased, while Bcl2 levels increased) and autophagy was inhibited (LC3II/I and Beclin-1 levels decreased, while p62 levels increased). MiR-133a targeted RAC1. RACY upregulation attenuated the inhibitory effects of miR-133a on PC12 cell apoptosis and autophagy. CONCLUSIONS Our data highlighted that miR-133a overexpression prevented apoptosis and autophagy in a cell model of MPP⁺-induced PD by inhibiting RAC1 expression.

The aim of this study was to investigate appropriate treatment strategies for recurrent intrahepatic hepatocellular carcinoma (HCC) in patients who fulfilled the Milan criteria at primary hepatectomy.A total of 124 patients who underwent curative-intent resection of HCC at our center between January 2007 and March 2014 were retrospectively enrolled; patients had initially fulfilled the Milan criteria, but developed intrahepatic recurrence. Seventy-four patients underwent transarterial chemoembolization (TACE) and another 50 patients underwent repeat resection (RR) or radiofrequency ablation (RFA). The recurrent HCCs were classified into intrahepatic metastasis and multicentric occurrence by pathologic analysis. Demographic and clinical data and overall survival rates were compared between the RR/RFA and the TACE groups. Subgroup analysis on the basis of the recurrence pattern (early recurrence or late recurrence) was carried out, and prognostic factors for survival were investigated.The 1-, 3-, and 5-year overall survival rates for the 124 patients after retreatment were 88.3, 55.4, and 44.3%, respectively. The 1-, 3-, and 5-year overall survival rates after retreatment were not significantly different between the RR/RFA and the TACE groups (P=0.140). Subgroup analysis showed that for late recurrence, survival in the RR/RFA group was better than those of patients in the TACE group (P=0.045).TACE may be as effective as RR or RFA for early intrahepatic recurrence, whereas RR/RFA is the preferred option for patients with late recurrence after curative resection of HCC who initially fulfilled the Milan criteria. Prognosis was determined by the number of recurrent tumors and the Child-Pugh class at the time of recurrence.

Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine ( 131 I) metuximab injection (Licartin), a novel 131 I-labeled HAb18G/CD147-specific monoclonal antibody F(ab') 2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56–63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles ( p p = 0.0019). Conclusion: Iodine ( 131 I) metuximab injection is safe and active for HCC patients.

Radioimmunotherapy may improve the outcome of hepatocellular carcinoma (HCC) patients by delivering targeted radiation to liver lesion tissue while relatively sparing nontarget tissues. This study was designed to observe the biodistribution, localization and imaging characteristics of 131I -labeled Metuximab in 24 patients with HCC to determine the diagnostic and therapeutic potential of this antibody.Twenty-four HCC patients were randomly divided into three groups to receive 18.5, 27.75 and 37 MBq/kg of 131I-labeled Metuximab per kilogram of body weight, respectively. 99mTc-sodium phytate was administered intravenously and the single photon emission computed tomography (SPECT) scanning was performed. After 48 h, 131I -labeled Metuximab was injected by hepatic artery intubation, and SPECT scan performed at 7 d. The percentage of absorbed 131I (%ID) and the time-dependent 131I tumor:nontumor tissue (T/NT) ratios were calculated at 12, 48, 96 and 192 h after injection.The positive Imaging result of MAb scanning in 24 patients showed that the iodine 131 conjugated to Metuximab was apparently accumulated more in hepatoma. Biodistribution studies of 131I-Metuximab in trial I demonstrated that the comparable % ID uptake in tumor (with a T/NT ratio at 12, 48, 96 and 192 h) to that in such normal organs, as thyroid, heart, lung, spleen and intestines were all more than one. The optimal imaging time for the highest T/NT ratio in liver was at 192 h.131I-labeled Metuximab could deliver relatively selective radiation to tumor tissues and may have potential efficacy in relieving hepatocellular carcinoma.

Summary Background As a bridge to liver transplantation or downstaging therapy for hepatocellular carcinoma (HCC) patients, preoperative transarterial chemoembolization (TACE) has potential risks in causing damage to hepatic artery (HA), resulting in severe postoperative complications. Aim To evaluate the impact of pre-TACE on postoperative hepatic artery complications (HAC) for HCC patients in a single liver transplant center. Materials and methods Clinical data of 450 HCC patients undergoing orthotopic liver transplantation (OLT) from January 2001 to December 2013 were retrospectively analyzed. Patients were divided into Group 1 (with pre-TACE) and Group 2 (without pre-TACE). Preoperative characteristics and postoperative HAC were compared. Results One hundred and eleven patients (69 men; median age, 37 ± 9.9 years) in Group 1 were compared with 339 patients (244 men; median age, 38.8 ± 8.0 years) in Group 2. Patients were comparable in donor/recipients characteristics between groups. Histological review for native liver samples showed that Edema was the most often seen complication following pre-OLT TACE (troncluar: 87 vs 9; segmental: 91 vs 10; liver parenchyma: 93 vs 8; P = 0.000). Fibrosis, thrombosis and aneurysm were only seen in Group 1. There were no significant difference in postoperative HAC (5/111 (4.5%) vs 5/339 (1.5%), P = 0.131) between groups. Conclusion Our single institution experience showed that it might be safe to perform pre-TACE in HCC patients before OLT. It would not increase postoperative HAC risk.

To investigate the surgical strategy of diabetic foot (DF) and analyze the therapeutic efficacy.From July 2004 to July 2007, 36 patients (22 males and 14 females) with DF were treated, with an average age of 57 years(43-82 years). The disease course of diabetes was 3 months to 27 years (12 years on average) and the disease course of DF was 1 month to 2 years (7 months on average). According to Wagner classification of DF, there were 3 cases of grade 1, 12 cases of grade 2, 10 cases of grade 3, 7 cases of grade 4 and 4 cases of grade 5. The locations of ulcer were ankle and heel in 9 cases, medial part of foot in 14 cases, in lateral part of foot in 8 cases and sinus formation in 5 cases. The ulcer sizes ranged from 4 cm x 2 cm-18 cm x 9 cm. Initial management of these patients included control of blood sugar level, proper hydration, administration of antibiotics, treatment of coexisting diseases, and repeated debridements of wounds when necessary. Ulcers were treated with debridement and split skin transplantation in 3 cases of grade 1, with debridement and drainage of abscesses and split skin transplantation in 12 of grade 2, with debridement and transplantation of flap in 17 of grade 3 and grade 4, and with transplantation of fascial flap in 5 cases of sinus; ulcers were treated firstly with artery bypass of lower extremity, and then treated with local amputation of foot to avoid high-level amputation and to save more function of foot in 4 of grade 5.In 36 cases, wound in 31 cases (86.1%) cured primarily, wound did not heal in 1 patient (2.1%) and received re-amputation, there were 2 deaths because of infection with multiple organ failure postoperatively. Twenty-nine cases were followed up 8 months (range, 6 -15 months). Eight patients developed new ulcers, with 3 lesions in situ and 5 lesions in new site.Surgical regimen could play an important role in treatment of diabetic foot. According to different grades of DF, there were different strategies in dealing with the accompanied inflammation and ulcer. An active and comprehensive surgical treatment of DF could save the foot, avoid the high-level amputation and result in more functional extremity.

To study pharmacokinetics of injection of iodine-131 labelling MEI-TUO-XI monoclonal antibody (hepatoma monoclonal antibody HAb18 F(ab')2) in vivo. 24 cases of primary hepatocelluar carcinoma (PHC) were equally divided into the low dose group, middle dose group and high dose group. After the relevant injection was administrated into the hepatic artery of each case, intravenous blood and urine samples were separately collected at different time for determination of the radioactive count ratio (min(-1)). The proportion of 131I-HAb18 F(ab')2 in serum of each blood sample was determined, and the radioactive count ratio (min(-1)) of druggery for each blood sample was revised according to the proportion. The pharmacokinetic parameters were calculated using DAS ver 1.0 (Drug And Statistics for Windows) program. The component of urine radiomaterial was determined and the percentages of urine radioactivity in administration dosage were calculated. The catabolism of the injection with time accorded with dynamics two-compartment model. The catabolism product was mainly free-131I and was excreted via kidney; the urine radioactivity was 47.70%-51.16% of administration dosage during 120 h after administration of drug. Therefore, the pharmacokinetics of the injection can satisfy the clinical demands. The drug dose recommended for clinical use was 27.75 MBq of the injection for each kg of human body.

Before 131I-HAb18F(ab')2 administration, 24 cases of mid-term or advanced hepatocellular carcinoma(HCC) were given Lugol's Liquid to block the thyroid gland, and submitted to hepatic colloid imaging. The cases were randomly divided into 3 groups. Then 131I-HAb18F(ab')2 was injected into the target hepatic artery with doses of 0.5, 0.75, 1.0 mCi/kg, respectively. At the followed 10, 48, 96 and 192 hours, 131I-HAb18F(ab')2 distribution in human body was acquired by whole body dynamic image with Single photon emission computed tomography(SPECT). The results showsed that 131I-HAb18F(ab')2 in tumor tissue was significantly higher than that in normal liver tissue and other organs. This difference became obvious as time passed. 131I-HAb18F(ab')2 is stable in human body and it can combine with HCC tissue specifically. So it is a new medicine deserving further research for the treatment of HCC.