Objective To investigate the therapeutic effect of tokinolide B (TB) on renal ischemia-reperfusion injury (IRI) in mice and its underlying molecular mechanism. Methods Male C57BL/6J mice were randomly assigned into six groups with 10 animals per group: sham operation group (Sham group), sham operation + TB treatment group (Sham+TB group), renal IRI model group (IRI group), TB intervention group (IRI+TB group), ML385 pretreatment group (IRI+TB+ML385 group) and sham + ML385 control group (Sham+ML385 group). Serum samples and renal tissues were harvested 24 hours after renal IRI surgery. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured to evaluate renal function. The levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α in renal tissue homogenate were detected to assess inflammatory response, and hematoxylin-eosin (HE) staining was performed to observe pathological lesions in renal tissues. Transcriptomic analysis was conducted on renal tissues from the IRI group and IRI+TB group to screen relevant biological processes and signaling pathways. Malondialdehyde (MDA), glutathione (GSH) and ferrous ion (Fe²⁺) contents in kidney tissues were quantified. Real-time fluorescence quantitative polymerase chain reaction was used to detect the messenger RNA (mRNA) expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and acyl-CoA synthetase long-chain family member 4 (ACSL4). Western blot was adopted to determine the protein levels of nuclear factor E 2-related factor 2 (Nrf2), GPX4 and SLC7A11. Results Compared with the IRI group, the IRI+TB group exhibited decreased serum Scr and BUN concentrations, suppressed expression of renal IL-6, IL-1β and TNF-α, as well as alleviated renal pathological damage. Enrichment analysis demonstrated that DEGs induced by TB intervention were predominantly enriched in ferroptosis, oxidative stress and Nrf2-associated signaling pathways. Detection of ferroptosis-related biomarkers revealed that relative to the Sham group, the IRI group presented elevated MDA and Fe²⁺ levels, reduced GSH content, downregulated mRNA expression of GPX4 and SLC7A11, and upregulated ACSL4 mRNA expression. In contrast with the IRI group, the IRI+TB group showed lowered MDA and Fe²⁺ concentrations, elevated GSH level, upregulated GPX4 and SLC7A11 mRNA levels, and downregulated ACSL4 mRNA level (all P<0.05). Molecular docking verified that TB could bind stably to Nrf2 with a binding free energy of −32.6 kJ/mol. Western blot results indicated that the protein abundances of Nrf2, GPX4 and SLC7A11 in renal tissues were markedly higher in the IRI+TB group than those in the IRI group. ML385 pretreatment abrogated the renoprotective effect of TB against renal IRI (all P<0.05). Conclusions TB exerts protective effects against renal IRI in mice possibly by binding to Nrf2 to facilitate its nuclear translocation, subsequently activating the downstream Nrf2/GPX4/SLC7A11 signaling cascade to suppress ferroptosis.

Objective:To evaluate the clinical efficacy of multi-disciplinary single center's CCCG-HB-2016 regimen in the treatment of hepatoblastoma (HB) in children.Methods:Clinical data of 36 HB patients treated with CCCG-HB-2016 program from Aug 2016 to March 2020 were analyzed.Results:These 36 patients included 20 boys and 16 girls. The serum AFP was all higher than 2 792 ng/ml,there was a correlation between AFP and tumor risk stratification ( H=14.973, P<0.05). Twenty eight cases (77.78%) were epithelial type and 8 cases (22.22%) were mixed epithelial mesenchymal type.All children were treated by tumor resection combined with chemotherapy, and there was a correlation between tumor risk stratification and surgical resection of liver lobe ( H=8.847, P<0.05). The probability of bone marrow suppression in the low-risk group was 58.33% (35/60),that in the intermediate-risk group was 73.49% (61/83) and in the high-risk group was 80.23% (69/86).All 36 cases were followed up to March 31, 2020,with an average follow-up of 21.9 months and the median survival was 22.5 months.The overall survival rate (OS) and event-free survival rate (EFS) were 97.2% and 83.3% respectively. Conclusions:The multidisciplinary CCCG-HB-2016 regimen was with a high success rate and along with a high incidence of bone marrow suppression.

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
Adult ; COVID-19 ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects*

Objective To study the clinicopathological features of chronic inflammatory mass lesion of the pancreas.Methods The clinical data of 37 patients with focal chronic inflammatory mass lesion of the pancreas were retrospectively studied.Seventeen cases congruent with the standard clinical diagnostic of chronic pancreatitis were separated into group A;and Whipple procedure was carried out in two cases,resection of the body and tail of the pancreas in 2 cases,local resection in one case,and choledochojejunostomy in 12 cases.Those without the stander clnical features of Group A but with the features of pancreatic tumor were separated into Group B;and Whipple procedure was carried out in 4 cases,choledochojejunostomy in 16 cases.Results In group A,except for the local mass lesion,sclerosis of the whole pancreas was found in 88.2% of cases.Pathological examination showed proliferation of fibrous tissue with associated inflammation,as well as acinar atrophy,remnant islet cells,and ductular dilatation and focal calcification.While in Group B,only a local mass lesion of the pancreas was found in 19 cases.The pathological features were characterized histologically by proliferation of fibrous tissue with associated moderate or marked inflammation.No pancreatic carcinoma was found during 1 to 12 years follow-up of 33 cases.Conclusions Chronic inflammatory mass lesion of the pancreas showed the clinicopathological features of pseudotumoral pancreatitis.Internal drainage by choledochojejunostomy is suggested as its effective management.

Objective To evaluate the oncologic risks of skin sparing breast conserving surgery for carcinoma of breast at early stage.Methods Serial sections of skin overlying the tumor were done for pathological examination in 50 cases of early stage breast cancer after skin sparing breast conserving operation.Results In 50 cases of breast conserving surgery,the extent of skin removal was 0.5-1.0cm in 21 cases,1.0-1.5cm in 25 cases,and 1.5-2.0cm in 4cases.Skin involvement was found in one patient with stage Ⅱ breast cancer,and the rate of skin involvement was 2%.Skin involvement was closely related with the changes in skin overlying the tumor,but not with the tumor size,pathologic types or axillary lymph node metastasis.Conclusion The rate of skin involvement in early stage breast cancer is rare,therefore if there are no abnormal clinical manifestations in the skin,skin sparing breast conserving surgery is safe.