Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

Objective: To investigate trends in the disease burden of tumors among children aged 0 to 14 years in China in 1990 and 2019, so as to provide insights into management of pediatric tumors in China. Methods: The Global Burden of Disease 2019 data were retrieved from the Global Health Data Exchange, and the mortality and disability adjusted life years (DALYs) of pediatric tumors were evaluated among children at ages of 0 to 14 years in China in 1990 and 2019, and the disease burdens due to pediatric tumors in China were compared with the regions with different social population index (SDI). Results: The mortality of tumors decreased from 13.10/105 in 1990 to 4.96/105 in 2019 (a 62.17% reduction) among children aged 0 to 14 years in China, and the DALY rate decreased from 1 118.93/105 to 424.77/105 (a 62.04% reduction). The mortality and DALY rate of tumors decreased from 13.48/105 to 5.38/105, and from 1 147.09/105 to 458.65/105 among male children, and from 12.69/105 to 4.46/105, and from 1 088.22/105 to 384.94/105 among female children. The disease burden of pediatric tumors was concentrated among children at ages of 0 to 4 years. The three highest disease burdens of pediatric tumors were measured in leukemia, brain and nerve system tumors, and lymphoma in 2019. Compared with the regions with different SDI, the largest reductions were seen in the mortality and DALY rate of tumors among children at ages of 0 to 14 years in China, which were still higher than in middle, high-middle and high SDI regions. Conclusions The disease burden of tumors declined among children at ages of 0 to 14 years in China in 2019, compared with 1990; however, it is still higher than in middle and higher SDI regions. The disease burden of pediatric tumors was high among children at ages of 0 to 4 years and among male children, with leukemia, brain and nerve system tumors and lymphoma as predominant types.

Objective:To analyze the functional connectivity (FC) characteristics of sensory motor network (SMN) in patients with bipolar disorder type Ⅰ (BD-Ⅰ) by independent component analysis (ICA), and explore the correlation between abnormal SMN and clinical symptoms.Methods:Eighteen patients with BD-Ⅰ (BD-Ⅰ group) and 20 matched normal controls (HC group) were included.Both groups received resting state fMRI (rs-fMRI) scanning.Based on ICA-fMRI data, one-sample t-test and two-sample t-test were used to analyze the components of SMN and to explore abnormal brain regions between the two groups.Functional network analysis (FNC) was also used to explore the functional connectivity between SMN and other brain networks.Pearson correlation analysis were conducted by SPSS 17.0 to measure the potential associations between intra-and inter-network functional connectivity and age, education, score of Bech-Rafaelsen mania rating scale (BRMS), score of positive and negative syndrome scale (PANSS) and other indicators. Results:In BD-Ⅰ group, the functional connection in the right paracentral lobule (MIN: x=8, y=-32, z=68, t=4.86, P<0.001) and the right postcentral gyrus (MIN: x=41, y=-26, z=53, t=3.33, P<0.001) in SMN were higher than those in HC group.Compared with HC group, the connectivity value in patients with BD-Ⅰ increased between SMN-DAN (0.247±0.073, -0.078±0.080, t=-2.974, P<0.01, FDR adjusted), while the connectivity value decreased between SMN-DMN(-0.037±0.054, 0.272±0.067, t=3.520, P<0.01, FDR adjusted) and between SMN-rFPN(-0.034±0.055, 0.231±0.070, t=2.939, P<0.01, FDR adjusted). Conclusion:The sensorimotor network of patients with BD-Ⅰ has abnormal functional connections within and between networks, and FC values in some networks are positively correlated with manic symptoms, which may be part of the neural mechanisms of patients with BD-Ⅰ.

Objective To investigate the clinical prognosis of the liver transplant recipients diagnosed with hepatocellular carcinoma (HCC) complicated with microvascular invasion (MVI). Methods Clinical data of 3 447 HCC recipients undergoing liver transplantation were extracted from Surveillance, Epidemiology, and End Results (SEER) database of American National Cancer Institute. According to the incidence of MVI, all recipients were divided into MVI (n=376) and non-MVI groups (n=3 071). The clinical prognosis of liver transplant recipients was statistically compared between two groups by analyzing the 1-, 3- and 5-year overall survival (OS) and liver cancer specific survival (LCSS). Relevant clinical data including age, gender, race, pathological staging, tumor size, lymph node metastasis, distant metastasis, tumor-node-metastasis (TNM) staging and MVI were recorded in two groups. The independent risk factors of clinical prognosis of HCC recipients undergoing liver transplantation were analyzed by multivariate Cox regression model. The nomogram for predicting the clinical prognosis of the recipients was delineated. The accuracy of the prediction model was evaluated by the consistency index. Results In the non-MVI group, the 1-, 3-, 5-year OS and LCSS were 93.5%, 82.1%, 75.3% and 98.3%, 93.8%, 90.7%, significantly higher than 88.8%, 72.1%, 68.4% and 95.3%, 83.1%, 80.4% in the MVI group (all P < 0.05). Multivariate regression analysis showed that pathological staging, tumor size, lymph node metastasis, distant metastasis, TNM staging and MVI were the independent risk factors of OS and LCSS in HCC recipients undergoing liver transplantation (all P < 0.05). The nomogram consistency index was calculated as 0.624 (0.602-0.648). Conclusions MVI is an independent risk factor of the clinical prognosis of HCC recipients undergoing liver transplantation, which is significantly correlated with poor prognosis of the recipients. The nomogram based on MVI can predict the clinical prognosis of these recipients.

Objective To explore the clinical and technical essentials of hepatic arterial segmentation and reconstruction during split liver transplantation using pediatric deceased donor .Methods The clinical data were retrospectively analyzed for 15 pediatric deceased donor aged 4 .6-16 .3 years undergoing split liver transplantation from July 2017 to March 2019 .The donors were DBD (donation after brain death ,n=13) and DCD(donor after cardiac death ,n=2) .Thirty split liver transplantations were performed using these 15 pediatric deceased donors .The receptors were adult + child (n=5) and child + child recipients (n=10) . According to the Michels' classification ,the clinical types were I (n= 13) ,V (n= 1) and VI (n= 1) . Hepatic arterial segmentation :In type I hepatic arterial type donor liver ,proper hepatic artery was retained in right trilobar liver (n=8) ,low-age (< 7 years) donor liver (n=5) ,retaining proper hepatic artery in left liver & reconstructing right trilobe directly using right hepatic artery trunk (n= 4) .Methods of hepatic artery reconstruction :8-0 Prolene string was utilized under 4 .5 times magnifying glass for reconstructing hepatic artery in recipients aged under 4 years .Results Hepatic arterial segmentation and reconstruction were successfully completed .Hepatic arterial thrombosis occurred in 2 ./25 ecipients .The overall incidence of hepatic arterial complications was 6 .67％ .Conclusions For reducing the occurrence of arterial complications , arterial segmentation and reconstruction in pediatric deceased donor should be performed according to the size of donor liver and the characteristics of hepatic arterial classification .

Objective To investigate the role and mechanism of oncogene spindle and kinetochore associated complex subunit 3 (SKA3) in the proliferation regulation of hepatocellular carcinoma (HCC) cells. Methods The expression of SKA3 in HCC tissues and cells was detected by Western blot and RT-PCR. SKA3 overexpression group (Huh7-SKA3) and control group (Huh7-Vector) were constructed using lentivirus transfection. Cell models of SKA3 interference group (Huh7-shSKA3) and control group (Huh7-Scramble) were constructed as well. The ability of cell proliferation was detected by MTT assay and cell clony formation assay. The cell cycle was detected by flow cytometry, and the expression of cyclin related proteins was detected by Western blot and RT-PCR. The experimental data were compared byt test.Results The expression of SKA3 protein in HCC tissues and Huh7 HCC cells increased significantly, and the expression level of mRNA was respectively 15.46±2.10 and 9.26±0.80, significantly higher than 1.48±0.17 and 1.11±0.07 of normal liver tissues and normal liver cells LO2 (t=6.58, 10.08; P<0.05). The cell growth curve showed that the proliferation ability of cells in overexpression group was significantly better than those in control group, and the proliferation ability of cells in interference group was lower than those in control group. The number of cell clones in the overexpression group was 259±20, significantly higher than 97±11 in control group (t=9.12, P<0.05), and the number of cell clones in interference group was 11±2, significantly lower than 97±11 in control group (t=-8.13, P<0.05). The ratio of phase G2/M and phase S in overexpression group was respectively (5.5±0.6)％ and (41.9±3.6)％, and was correspondingly (15.8±1.5)％ and (31.9±3.3)％ in control group, and significant differences were observed (t=-10.89, 6.39; P<0.05). The ratio of phase G1/G0 and phase S in interference group was respectively (71.7±6.1)％ and (20.2±2.9)％, and was correspondingly (53.4±5.4)％ and (31.3±4.2)％ in control group, and significant differences were observed (t=8.59,-5.17;P<0.05).Conclusions SKA3 is highly expressed in HCC and can promote the proliferation of HCC cells, which may be related to its promotion of cell cycle from phase G1 to phase S.

The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin II type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.
Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; Animals ; Apoptosis ; drug effects ; Benzazepines ; administration & dosage ; Doxorubicin ; Drug Therapy, Combination ; Fas Ligand Protein ; Glomerulosclerosis, Focal Segmental ; chemically induced ; drug therapy ; pathology ; Kidney ; pathology ; Male ; Membrane Glycoproteins ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tetrazoles ; administration & dosage ; Tumor Necrosis Factors ; biosynthesis ; genetics ; Valine ; administration & dosage ; analogs & derivatives ; Valsartan ; fas Receptor ; biosynthesis ; genetics

AIM　To extend the approach of the act ion of ganoderma polysacchride on intracellular signal events in T cells. METHODS　Laser scanning confocal microscope imaging of the calcium and p H fluorescent indicator dye Fluo-3/AM and SNARF-1/AM were used to determine th e kinetic changes of ［Ca2+］i and ［pH］i in murine T cells induced b y a ganoderma polysacchride,designated GLB7. RESULTS　It was fou nd that GLB7(20 mg*L-1) could increase ［Ca2+］i and ［pH］i at 1 min were 334.7%±16.4%(n=3)、171.6%±10.4%(n=3) respectively. T he increase in ［Ca2+］i induced by GLB7 was due to the influx of extr acellular Ca2+ and intracellular Ca2+ release through both IP3-se nsitive and IP3-insensitive Ca2+ stores, and increase in ［pH］i indu ced by GLB7 was relative to Na+/H+ exchange systems and ［Ca2+］i. GLB 7 did not influence ［Ca2+］i and ［pH］i in murine T cells induced by Con A(3 mg*L-1). CONCLUSION　Stimulation of the increase in ［Ca2+］i and ［pH］i may be an important channel for gano derma polysacchrides to achieve their pharmacological actions.

AIM：To investigated the effects of Ganoderma polysaccthride(GLB7)on protein kinase A(PKA) and protein kinase C(PKC) activitives in murine T cells.METHODS：A new ion-pair reversed-phase high liquid chromatography method was used to determinate the activities of PKA and PKC in T cells.RESULTS：GLB7 could markedly increase the activities of PKA and PKC in murine T cells in a dose-dependent manner.The peak time was at 5 min and 20 min and the activities of PKA and PKC returned to basic level at 20 min and 1.5h respectively.GLB7 could induce translocation of PKC and antagonize the inhibition effect of staurosporine(10μ mol· L-1) on PKC in T cells.CONCLUSION：The immunopotentiating and antitumour effects of Ganoderma polysacchride may be associated with its activation on PKA and PKC in murine T cells.