Objective: To explore the function of serum leptin in COPD patients with malnutrition, and to investigate the relationship between leptin and TNF-?. Methods: A total of 81 subjects (47 COPD patients and 34 control subjects) participated in this study. The 47 COPD patients were divided into 2 groups: group COPD Ⅰ (patients without malnutrition during stable disease, n=29), group COPDⅡ(patients with malnutrition during stable disease, n=18).To eliminate the effect of sex differences, all the patients and controls were male. Body mass index (BMI), percent ideal body weight (IBW%), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference(MAMC),serum leptin and tumor necrosis factor-?(TNF-?) levels, serum prealbumin (PA), serum transferrin (TF), serum albumin(Alb),total lymphocytes count (TLC), forced expiratory volume in one second (FEV_1), maximal inspiration pressure(MIP)and maximal expiration pressure(MEP)were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-? levels were measured by ELISA. The between group difference and correlation of these parameters were analysed. Results: (1)Serum leptin levels were significantly lower in group COPDⅡ (4.07?3.42 ?g/L) than in group COPD Ⅰ(9.72?6.67 ?g/L)and controls(8.21?5.41 ?g/L, P

Objective To compare clinical features,pulmonary functions,chest imaging and prognosis between combined pulmonary fibrosis and emphysema syndrome (CPFE) and idiopathic pulmonary fibrosis(IPF) without emphysematous changes in elderly patients.Methods 88 elderly IPF patients in Beijing hospital from January 2000 to October 2012 were divided into CPFE (n=30) and IPF (n =58) groups according to the CT imaging.Clinical features,blood gas analysis,pulmonary function,chest CT and survival time were compared between the two groups.Results 30 CPFE patients with the mean age of(75.5 ±7.6) years and 58 IPF patients without emphysema with the mean age of(73.7±6.8) years were enrolled.The proportions of male patients,smoking history and mortality were higher in CPFE patients than in IPF group(86.7％ vs.63.8％,28 vs.36,76.7％ vs.43.1％,x2 =5.09,9.74,8.98,P＜0.05 or 0.01).CPFE patients had a higher force vital capacity(FVC) and total lung capacity(TLC) as compared with IPF group [(2.6±0.9) L vs.(2.1± 0.5) L,(5.4±1.9) L vs.(4.4±1.1) L,t=2.69,2.35,P＜0.01 or 0.05].There were no significant differences in forced expiratory volume in one second(FEV1) and the diffusion capacity for carbon monoxide(DLCO) between the two groups.The main type of emphysema by HRCT scan were centrilobular emphysema in CPFE patients.There were lower median survival time in CPFE group than in IPF group [(3.0±0.2) years vs.(4.0±1.0) years,x2=4.50,P＜0.05].Conclusions The majority of elderly CPFE patients are males and smokers.The lung volume is increased in elderly CPFE patients as compared with IPF patients.Centrilobular emphysema is the primary type in CPFE patients.The prognosis is worse in elderly CPFE patients than in IPF patients.

Oral hydroxycamptothecin nanosuspension (HCPT-Nano) with high supersaturated dissolution level, high permeation and well physical stability, was manufactured by microprecipitation-high press homogenization method. Its pharmaceutical properties were investigated, such as size and distribution, zeta potential, particle shape, physical existence condition, supersaturated dissolution level and so on. Particle size was measured by laser diffraction, and the mean diameters before and after lyophilization were 138 +/- 11.72 nm and 175 +/- 12.74 nm, respectively, for HCPT-Nano. Zeta potentials of HCPT-Nano was over -20 mV. The nanoparticles, being observed by transmission electron microscopy (TEM), were claviform or column in shape. DSC and X-ray diffraction revealed that HCPT existed in the form of crystal for HCPT-Nano. And HCPT-Nano could maintain higher supersaturated dissolution level for long time. So it supplied the possibility of improving oral bioavailability of HCPT when combining together admoveatur of P-gp inhibitor, CsA.

Objective:To analyze the relations of blood-brain barrier (BBB) integrity with clinical features and their response to immunotherapy in patients with autoimmune encephalitis (AE).Methods:One hundred and forty-seven AE patients confirmed in Department of Neurology, First Affiliated Hospital of Zhengzhou University from August 2015 to December 2021 were chosen; their clinical and laboratory data were collected retrospectively. In accordance with cerebrospinal fluid (CSF) albumin/serum albumin (QAlb) value of 7, patients were classified into normal BBB group ( n=101, QAlb value ≤7.00) and damaged BBB group ( n=46, QAlb value >7.00). Modified Rankin Scale (mRS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) were used to evaluate the severity on admission and 30 d after first-line immunotherapy; and good immunotherapy responsiveness was defined as CASE or mRS scores 30 d after first-line immunotherapy lower than those at admission. Differences of general data, clinical manifestations, CSF and peripheral blood biochemical results, and response to immunotherapy between the two groups were compared and analyzed. Results:The damaged BBB group had significantly higher proportions of patients with decreased consciousness level (58.7% vs. 37.6%), increased CSF protein, increased immunoglobulin G (IgG) and increased 24 h intramural IgG synthesis rate, and significantly higher fibrinogen in peripheral blood than normal BBB group ( P<0.05). On 30 th d of treatment, mRS scores of patients in damaged BBB group were significantly higher than those of patients in normal BBB group ( P<0.05), and the differences of CASE scores and mRS scores before and after treatment in damaged BBB group were significantly lower than those in normal BBB group (0.50±0.46 vs. 3.24±2.93, 0.70±0.62 vs. 1.15±1.04, P<0.05). In damaged BBB group, good immunotherapy response rate in patients receiving single immunotherapy was significantly lower than that in patients receiving two or three combinations of first-line immunotherapy ( P<0.05). Conclusion:BBB integrity is closely related to clinical characteristics and response to immunotherapy of AE; combined first-line immunotherapy is recommended for AE patients with BBB injury.

Objective:To investigate the clinical significance of tumor budding as an indicator of postoperative distant organ metastasis after radical gastrectomy in elderly patients diagnosed with gastric cancer.Methods:The clinical and pathological data of 124 elderly patients who experienced metastasis after undergoing radical gastrectomy were retrospectively analyzed.The analysis was conducted from March 2015 to June 2022, focusing on the clinicopathological factors that influenced the occurrence of postoperative distant metastasis in these patients.Tumor budding in gastric cancer tissues was assessed using hematoxylin-eosin staining, and its clinical significance was analyzed.Results:The tumor budding grade of gastric cancer tissues showed a significant correlation with vascular invasion( χ2=6.731, P=0.009), the number of lymph node metastases( rs=0.481, P<0.001), and the time of distant metastasis( rs=-0.450, P<0.001).In the univariate analysis, factors such as tumor budding grade, tumor size, vascular invasion, postoperative chemotherapy, cancerous nodule, preoperative serum carbohydrate antigen 125, and the number of lymph node metastases were found to influence distant metastasis-free survival after radical gastrectomy in elderly patients(all P<0.05).The multifactorial analysis also indicated that tumour outgrowth grade was an important independent prognostic factor for postoperative distant metastasis in elderly gastric cancer patients( HR=3.731, P<0.001). Conclusions:The findings of this study indicate that tumor budding may serve as a potential marker for predicting distant organ metastasis in elderly patients who have undergone radical gastrectomy.This discovery holds significant clinical implications.

Objective:To investigate the regulatory effects and mechanism of mannan-binding lectin (MBL) on adipogenic differentiation of 3T3-L1 preadipocytes.Methods:3T3-L1 preadipocytes were induced to differentiate into adipocytes in vitro, and stimulated with different concentrations of MBL (0, 1, 10, 20 μg/ml). Firstly, changes in cell proliferation ability were detected by CCK-8. Then lipid accumulation was analyzed by Oil red O staining and intracellular triglyceride content determination. Further, the expression of adipogenic differentiation-related factors PPARγ and C/EBPα at protein and mRNA levels were detected by Western blot and qRT-PCR, respectively. Finally, Western blot was used to analyze the expression and phosphorylation of Akt, a signal molecule related to adipogenic differentiation. Results:MBL at the concentrations of 0, 1, 10 and 20 μg/ml had no effect on the proliferation of 3T3-L1 preadipocytes. The level of triglyceride in MBL treatment groups decreased in a dose-dependent manner on 3 d after 3T3-L1 preadipocyte differentiation. Results of Oil red O staining showed that the number of lipid droplets in MBL treatment groups reduced significantly, and the absorbance values also decreased significantly in a concentration-dependent manner. Western blot and qRT-PCR results showed that the expression of PPARγ and C/EBPα at both protein and mRNA levels in MBL treatment groups decreased significantly in a dose-dependent manner, and the phosphorylation level of Akt was significantly down-regulated as well.Conclusions:MBL regulates the adipogenic differentiation of 3T3-L1 preadipocytes via Akt signaling pathway.

Background: Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process. Methods: β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. Results: Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR- 8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected β-cells. Conclusion These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.

ObjectiveTo determine whether HBV DNA polymerase is associated with T-cell failure and thus mediates the immune escape of HBV-related hepatocellular carcinoma （HCC） tumor cells， and to investigate the specific molecular mechanisms. MethodsLiver cancer cell lines Huh7 and HepG2 stably transfected with HBV DNA polymerase expression plasmid with Flag （Flag-HBV-P） and intercellular adhesion molecule-1 （ICAM1） were co-cultured with Jurkat cells， and MTT assay， qRT-PCR， and ELISA were used to measure Jurkat cell proliferation， activation （CD69 expression）， and secretion of the cytokine IFN-γ. RNA-seq was used to screen for differentially expressed immune-associated molecules between stably transfected cell lines and control cells， and mRNA half-life and protein half-life assays were used to determine the specific levels of the immune-associated molecules that were affected by HBV DNA polymerase. Related websites were used to predict the transcription factors that may bind to the promoter region of this immune-associated molecule， Western blot was used to verify the effect of transcription factors on the immune-associated molecule， and rescue experiment was used to determine whether HBV DNA polymerase affects the expression level of the immune-associated molecule through this transcription factor. The independent-samples t test was used for comparison between two groups. ResultsThe experimental group had significant reductions in Jurkat cell proliferation， activation， and cytokine secretion compared with the control group （all P<0.01）. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had significant reductions in the mRNA and protein expression levels of ICAM1 （all P<0.01）. Website prediction identified the ICAM1 promoter and preliminarily highlighted NFKB1， RELA， and STAT3. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had a significant reduction in the protein expression level of p65 （all P<0.01）. After p65 overexpression， there was a significant increase in the protein expression level of ICAM1， and after the expression of p65 was reduced， there was a significant reduction in the protein expression level of ICAM1 （all P<0.01）. In the rescue experiment， there was no significant difference in the protein expression level of ICAM1 between the control group and the experimental group after p65 overexpression （all P>0.05）. After the overexpression of ICAM1， there were no significant differences in the proliferation， activation， and cytokine secretion of Jurkat cells between the control group and the experimental group （Huh7 and HepG2 cell lines） （all P>0.05）. ConclusionHBV DNA polymerase downregulates the level of ICAM1 to mediate HCC immune escape by inhibiting the expression of p65 in NF-κB.

Cancer， one of the deadliest diseases caused by cells escaping homeostasis， abnormal proliferation， and abnormal differentiation， is fast becoming one of the most burdensome diseases of this century. With decades of human research and cognitive changes in cancer， cancer treatment is also developing rapidly， but there is still a lack of effective treatment and countermeasures. Especially， the search for safe， efficient， and non-toxic drugs has become a long-term goal in the field of cancer. Saponins extracted and separated from traditional Chinese medicine can improve cancer through various pathways and have almost no toxic side effects. Therefore， the research on the anti-cancer effect of saponins is heating up. It is found that saponins play anti-tumor roles by inhibiting proliferation， metastasis， and angiogenesis of cancer cells， promoting apoptosis of cancer cells， inducing autophagy of tumor cells， and regulating miRNA expression and immune functions. Chinese herbal medicine saponins can regulate secretory glycoprotein /β-catenin （Wnt/β-catenin）， adenylate activated protein kinase （AMPK）， nuclear transcription factor-κB （NF-κB）， mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Janus kinase/activator of signal transduction and transcription 3 （JAK/ STAT3）， hypoxia-inducible factor-1α （HIF-1α）， Toll-like receptor （TLR）， and other related signaling pathways to get involved in the proliferation， metastasis， angiogenesis， apoptosis， autophagy， and other processes of cancer cells， thus interfering with the progression of cancer. Therefore， the focus of this review is to update the discovery and evaluation of Chinese herbal medicine saponins with anti-cancer properties， clarify their mechanism of action， including the progress of related signaling pathways， and deepen the understanding of the anti-cancer function of Chinese herbal medicine saponins， so as to provide a new perspective and direction for the prevention and treatment of tumors by traditional Chinese medicine and better promote the development and utilization of resources.