Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

Objective To compare the application effect of intermittent androgen deprivation(IAD)and continued androgen deprivation(CAD)on advanced prostate cancer and influence on prognosis.Methods The patients with advanced prostate cancer were divided into treatment group(86 cases)and control group(62 cases)according to the cohort method.The treatment group was given IAD regimen(subcutaneous injection of 3.6 mg goserelin once every 28 days)combined with oral administration of flutamide(250 mg every 3 times a day)or combined with oral administration of bicalutamide(50 mg once a day),and the control group was treated with CAD regimen(bilateral orchiectomy combined with continuous flutamide or bicalutamide orally,with the same dosage as the treatment group).The observation follow-up time of both groups was ≥9 months.Efficacy,serum total testosterone(TT),prostate specific antigen(PSA)and vascular endothelial growth factor(VEGF)were compared between the two groups after treatment,and the side effects of treatment,quality of life[Functional Assessment of Cancer Therapy-Prostate(FACT-P)]and disease progression were evaluated.Results At 9 months after treatment,the objective response rates(ORR)in treatment group and control group were 30.99％(22 cases/71 cases)and 29.09％(16 cases/55 cases),and the disease control rates(DCR)were 71.83％(51 cases/71 cases)and 69.09％(38 cases/55 cases)respectively(P＞0.05).Serum TT levels in treatment group and control group were(25.53±9.44)and(22.51±8.28)ng·dL-1,PSA levels were(4.48±1.02)and(4.32±0.95)ng·mL-1,and VEGF levels were(121.03±35.26)and(118.65±33.42)pg·mL-1 respectively(all P＞0.05).The incidence rates of hot flash in treatment group and control group were 21.13％and 56.36％,the incidence rates of breast swelling pain were 16.90％and 34.55％,and the incidence rates of osteoporosis were 8.45％and 25.45％respectively(all P＜0.05).The scores of physical condition of FACT-P in treatment group and control group were(24.15±4.22)and(20.28±3.71)points,the scores of life condition were(20.28±2.94)and(17.81±2.84)points,scores of prostate cancer specific(PCS)module were(33.21±6.32)and(28.42±5.43)points,respectively,the difference were all statistically significant(all P＜0.05).The cumulative progression-free survival rates in treatment group and control group were 61.97％and 58.18％(P＞0.05).Conclusion IAD is as effective as CAD in the treatment of advanced prostate cancer and has a similar effect on the prognosis of patients,but the former one has fewer side effects of treatment and helps to improve the quality of life of patients.

Objective To investigate the effect of high-frequency irreversible electroporation(H-FIRE)in the ablation of pig pancreatic tissue.Methods Laparotomy was conducted in this study,and needle electrodes were used to release electric pulses in 12 pigs.Three sets of parameters were established for ablation at the low,medium,and high values of field strength(1 000 V/cm,1 500 V/cm,and 2 500 V/cm).The groups were compared in terms of the data including postoperative recovery,ablation area,and histopathological features to validate the safety and efficacy of H-FIRE in the ablation of porcine pancreatic tissue.The paired t-test was used for comparison of continuous data between two groups.Results All pigs in the experiment survived and showed a good effect of ablation.The histopathological analysis of all groups showed thorough and effective ablation,with a clear boundary between the ablated area and the normal tissue area.The mean ablation area in the low,medium,and high field strength groups was 30.96±3.73 mm2,51.93±25.26 mm2,and 108.90±55.23 mm2,respectively,and the high and medium field strength groups had a significantly larger ablation area than the low field strength group(both P<0.05),while there was no significant difference in ablation area between the medium and high field strength groups(P>0.05).Conclusion H-FIRE ablation is safe and effective for porcine pancreatic tissue under specific ablation parameters.

Objective:To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid(PUFA)against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.Methods:The experimental animals were divided into 4 groups:wild-type mice normal control group,mfat-1 transgenic mice normal control group,wild-type mice model group and mfat-1 transgenic mice model group.The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model,while the mice in the normal control group were injected intraperitoneally with an equal amount of saline,and their status was observed and their body weight was measured daily.Peripheral blood was taken after 14 day for routine blood analysis,and the content and proportion of PUFA in peripheral blood were detected using gas chromatography.Bone marrow nucleated cells in the femur of mice were counted.The histopathological changes in bone marrow were observed by histopathological staining.The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.Results:Compared with wild-type mice,mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin.Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes,erythrocytes,platelets and haemoglobin in peripheral blood of myelosuppressed mice.The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin.Flow cytometry and PCR showed that,compared with wild-type mice model group,the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced(P＜0.001),and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased(P＜0.01),while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced(P＜0.001,P＜0.05).Conclusion:Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells,increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.

Aim To investigate the preventive and therapeutic effects of the mfat-1 gene therapy on exper-imental autoimmune encephalomyelitis in mice.Meth-ods mfat-1 gene therapy was used to render the host endogenous capability of producing ω-3 PUFAs,con-comitantly reduce the levels of ω-6 PUFAs,and change the proportion of ω-3/ω-6 PUFAs.Then,the levels of PUFAs in blood were analyzed by gas chromatography.The neurological deficits in mice were evaluated by neurological dysfunction score.HE staining and LFB staining of mouse spinal cord slices were used to ob-serve central nervous system inflammation infiltration and demyelinating lesions.Flow cytometry microsphere microarray technology was used to detect the content of cytokines in serum.Results The mfat-1 gene therapy could significantly raise the proportion of ω-3/ω-6 PU-FAs(P＜0.05),markedly delay the incubation period and peak period and reduce neurological dysfunction scores(P＜0.05),and improve inflammation and de-myelination of spinal cords(P＜0.05).It could also greatly increase the levels of IL-2,IFN-γ,IL-4 and IL-17 in serum(P＜0.05).Conclusion The pro-portion of ω-3/ω-6 PUFAs in blood circulation en-hanced by mfat-1 gene therapy can effectively prevent and treat experimental autoimmune encephalomyelitis in mice.

Humans ; Mpox (monkeypox) ; China

Objective     To investigate the risk factors for postoperative complications Clavien-Dindo classification≥grade Ⅱ after lung cancer surgery. Methods     The patients who underwent lung cancer surgery in a multicenter observational study from November 2017 to January 2020 were included. The Clavien-Dindo classification of postoperative complications was analyzed. Logistic regression was used to identify the risk factors for complications≥ gradeⅡ. Results     A total of 388 patients were enrolled, including 203 males and 185 females with a mean age of 56.14±10.36 years. The incidence of postoperative complications was 25.52% (99/388) after lung cancer surgery and the incidence of complications≥gradeⅡ was 20.10% (78/388). The five most common postoperative complications were pneumonia (6.96%), prolonged pulmonary air leak (>7 days, 5.67%), incision dehiscence (4.64%), arrhythmia (3.87%), and postoperative pleural effusion (3.35%). Multivariate analysis showed that open surgery [reference: uniportal thoracoscopic surgery, OR=2.18, 95%CI (1.01, 4.70), P=0.047], extended resection [reference: sublobar resection, OR=2.86, 95%CI (1.11, 7.19), P=0.030; reference: lobectomy, OR=2.20, 95%CI (1.10, 4.40), P=0.026] and operative time≥3 h [OR=2.07, 95%CI (1.12, 3.85), P=0.021] were independent risk factors for postoperative complications≥gradeⅡ after lung cancer surgery. Conclusion     Surgical approach, extent of resection and operative time are independent influencing factors for postoperative complications≥gradeⅡ after lung cancer surgery.

Objective To investigate the effect of T cell immunoreceptor with Ig and ITIM domains (TIGIT) on the function of CD8⁺ T cells in the lungs of Plasmodium infected mice. Methods The lungs of the mice infected with Plasmodium yoelii were isolated, weighed and photographed after 12 days' infection. After dissolution, lung lymphocytes were isolated, counted and stained, and then the contents of CD8⁺ and TIGIT⁺CD8⁺ T cells were detected by flow cytometry. The expressions of L selectin (CD62L), CD69, programmed death 1 (PD-1), CD25, and C-X3-C motif chemokine receptor 1 (CX3CR1) on TIGIT⁺CD8⁺ T cells were detected by flow cytometry. After stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, the ability of TIGIT⁺CD8⁺T cells to secrete interferon γ(IFN-γ), interleukin 21 (IL-21), IL-4, IL-17, and IL-10 was detected. Results The body mass of mice with Plasmodium infection was reduced. The lungs became darker, and the ratio of the lung mass to body mass was significantly increased. Compared with the normal mice, the percentages and absolute quantity of CD8⁺ and TIGIT⁺CD8⁺ T cells in the lungs of the infected mice were significantly increased. The percentage of TIGIT⁺CD8⁺ T cells expressing CD62L in the infected group was significantly lower, while the percentage of the CD69, PD-1, and CX3CR1 cells were significantly higher than that of TIGIT⁺CD8⁺ T cells from the normal mice. The percentages of TIGIT⁺CD8⁺ T cells secreting IL-21, IL-4, IL-17 and IL-10 cells in the infected group were significantly lower. Conclusion The lung lesions from mice with Plasmodium infection are obvious, the numbers of TIGIT⁺CD8⁺ T cells increase, and these cells express a variety of activation-related molecules, but the ability to secrete cytokines is reduced.
Animals ; Mice ; CD8-Positive T-Lymphocytes ; Cytokines/metabolism* ; Interferon-gamma/metabolism* ; Interleukin-10/metabolism* ; Interleukin-17/metabolism* ; Interleukin-4/metabolism* ; Lung/metabolism* ; Malaria/metabolism* ; Plasmodium yoelii/metabolism* ; Programmed Cell Death 1 Receptor/metabolism*

Hepatocellular carcinoma (HCC) is the most common primary hepatic malign-ancy in clinic. The prognosis of patients remains extremely poor because of the high malignancy and easy recurrence and metastasis of HCC. In recent years, the roles of platelets in promoting the malignant progression of HCC have increasingly attracted much attention. It is known that platelets could promote HCC cells proliferation and invasion through tumor microenvironment. On the other hand, platelets are capable to promote HCC cells distant metastasis by facilitating tumor cells evasion of immune surveillance. Besides, the platelet-derived growth factors and proangiogenic factors are also involved in the proliferation, invasiveness, and neovascularization of HCC. In addition, patients with HCC normally have a background of cirrhosis, and it is still controversial that whether the thrombocytopenia by portal hypertension and hypersplenism can promote the malignant progress of HCC. In view of this, the diagnostic and prognostic value of platelet levels, as well as platelet-associated scores in HCC have increasingly become research focus. The authors elaborate the detailed mechanisms of platelets in malignant progression of HCC, and discuss the recent research progress of platelets as effective diagnostic or prognostic tools for the assessment of HCC, which is of great importance to optimize the current treatment regimen and explore novel therapeutic strategies against HCC.