Humans ; Shwachman-Diamond Syndrome ; Myelodysplastic Syndromes/therapy* ; Transplantation, Homologous ; Hematopoietic Stem Cell Transplantation ; Transplantation Conditioning

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3⁺T cells were deficient in 124 cases (124/192, 66.31%). CD8⁺T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8⁺T cells were positively correlated with CD3⁺T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.
Adenocarcinoma/pathology* ; B7-H1 Antigen/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Humans ; Inflammation/pathology* ; Lymphocytes, Tumor-Infiltrating/metabolism* ; Pancreatic Neoplasms/pathology* ; Prognosis ; Tumor Microenvironment

Infertility with diminished ovarian reserve(DOR) is a major problem in the field of reproductive health and it has attracted great attention worldwidely.Function deficiency of the kidney is one of the fundamental pathogenesis for DOR.Traditional Chinese medicines(TCMs) have a long history with rich experience for the treatment of infertility.Some TCMs are very effective in the treatment of kidney deficiency for infertility with DOR.The integrated TCMs and western medicine,and combination of disease differentiation and syndrome differentiation may help for diagnosis and treatment of infertility with DOR.We adopt the concept of unified treatment for special disease,and the methods and principle of treatment can be used.Therefore,we adopt the TCM concept of kidney-tonifying,blood-nourishing,liver-dispersing and spleen-invigorating.The TCMs kidney-tonifying formulae are added and subtracted.TCMs can regulate the reproductive function via multiple systems for simultaneous conditioning of follicular development and ovulation.At the same time,a hypothesis of " simultaneous conditioning of follicular development and ovulation" was proposed.Two-stage therapy with integrated TCMs and western medicine has been used,mainly for increasing the number of eggs,and improving follicle quality.The goal is to achieve simultaneous conditioning of follicular development and ovulation and ultimately for effective treatment of infertility with DOR.

OBJECTIVE: To explore the effectiveness and safety of the combined treatment with acupuncture and venlafaxine hydrochloride on depression in terms of the microstructure change of white matter fiber tracts of brain based on diffusion tensor imaging technology (DTI). METHODS: The prospective study design was adopted. All of 60 patients with depression were randomized into an acupuncture-medication group and a medication group, 30 cases in each one. In the medication group, venlafaxine hydrochloride was used, 75 mg per day in the 1st week, 150 mg per day in the 2nd week and 225 mg per day from the 3rd to 6th week. In the acupuncture-medication group, on the base of the treatment in the medication group, acupuncture was combined. Baihui (GV 20) and Yintang (GV 29) were the main acupoints. The supplementary acupoints were selected according to the clinical symptoms of individuals. The needles were retained for 30 min. Acupuncture was provided once every 2 days, 3 times a week. The consecutive 12 weeks of treatment were required in the two groups. Additionally, a normal group was prepared with 30 healthy volunteers. Separately, before treatment, in 2, 8 and 12 weeks of treatment, Hamilton's depression scale (HAMD-17), Beck depression inventory scale (BDI) and the antidepressant side effect scale (SERS) were adopted to evaluate the effectiveness and safety of the two groups. Moreover, before and after 12 weeks of treatment, DTI was adopted to detect the fractional anisotropy score (FA) of each brain region in the patients. RESULTS: After treatment, the scores of HAMD-17 and BDI were all reduced in the two groups (<0.05). In 8 and 12 weeks of treatment, the scores of HAMD-17 and BDI in the acupuncture-medication group were less than those in the medication group (<0.05). The difference in SERS score was not significant statistically between the two groups (>0.05). Compared with the healthy volunteers, FA scores in 6 brain regions changed obviously in the patients with depression, including the white matter of bilateral frontal lobes, splenium of corpus callosum, left cingulated gyrus, white matter of bilateral inferior temporal gyrus, white matter of bilateral inferior parietal lobe and white matter of bilateral deep temporal occipital region separately. Before treatment, the differences in FA scores of these 6 brain regions were not significant statistically between the two groups (>0.05). After treatment, FA scores in the white matter of bilateral frontal lobes, white matter of bilateral inferior temporal gyrus and white matter of bilateral deep temporal occipital region in the acupuncture-medication group were all higher than those in the medication group (<0.05). CONCLUSION Acupuncture repairs the brain white matter fiber tracts in some brain regions to certain extent and the therapeutic effects are enhanced with the adjuvant medication of venlafaxine hydrochloride.
Acupuncture Therapy ; Brain ; Depression ; therapy ; Diffusion Tensor Imaging ; Humans ; Prospective Studies ; Venlafaxine Hydrochloride

BACKGROUND: With the development of 3D printing technology, organ and tissue construction can be achieved by constructing a three-dimensional scaffold that is conducive to cell growth. OBJECTIVE: To solve the scaffold over-accumulation during 3D printing.METHODS: Fluent, a finite element analysis software developed by ANSYS Company in the United States, was used to analyze the extrusion process of print heads and to obtain suitable viscosity and extrusion pressure of materials for the 3D printing of cellulose gel composites. We then compared simulation results with experimental results. RESULTS AND CONCLUSION: The error between simulation results and experimental results was less than 5%. The simulated values at a kinetic viscosity of 45 and a pressure of 0.10-0.12 MPa solved the phenomenon of over-accumulation of cellulose gel composites during the 3D printing process, ensuring enough space for the 3D printed scaffold.

We investigated the endemic situation of alveolar echinococcosis (AE) in Nileke County,Yili Prefecture,Xinjiang and its genetic diversity of Echinococcus multilocularis.Human AE cases in the county were retrospectively investigated including their location and surrounding ecological conditions.Sequence detection and analysis of nad2,cob gene fragments of AE mtDNA from patients was used to identify genotype variation.Results showed that a total of 48 AE cases were diagnosed and the first AE patient was identified in 1989 in the county.The 45.8％ of AE cases were found in the recent 5 years (2011-2015) and annual prevalence was 1.7 per 100 000.The patients were distributed along the Kashgar River,particularly intensive in Wulasitai Township.The 38.6％ of the patients were aged arranged 35-44 years old,64.6％ were male and 95.8％ were farmers and herdsmen.AE cases were confirmed further and there was only one haplotype by sequencing analysis from 11 AE clinical patients in the county.It suggests that Nileke County is AE foci,and alveolar echinococcosis with sequences conserved is an emerging disease in the county.

[Objective]To establish a reliable and accurate preimplantation genetic diagnosis (PGD)method using multiple dis?placement amplification (MDA), which can be applied to the diagnosis of X-linked severe combined immunodeficiency disease (X-SCID).[Methods]Haplotype analysis for the X-SCID family was performedusing five short tandem repeats (STR) markers flanking the both sides of the interleukin-2 (IL-2) receptor gamma chain (IL2RG) gene. MDA technique was used for single-cell whole genomic amplification. The products were used as template in polymerase chain reaction (PCR) of informative STR markers found by linkage analysis for haplotype analysis as well as sequencing of the IL2RG gene exon 5.The amelogenin (AMEL) locus was used to do sex diag?nosis.[Results]Linked analysis revealed 3 STR markers were informative. The method was evaluated with 10 single lymphocytes and 10 single blastomeres. MDA was successful in all single cell. The detection efficiency of gene sequencing of pathogenic IL 2RG exon5 was 100%. The PCR efficiency of 3 STR informative markers and AMEL was 96.3%(77/80)and the average allele drop-out (ADO) rate was 11.5%(7/61). A cycle of PGD was performed on the family, and seven embryos were diagnosed, two of which were normal embry?os. Twin pregnancy occurred after transplantation which were given a healthy baby boy and a healthy baby girl.[Conclusion]In this study, multiple displacement amplification combined with specific amplification/sequencing of pathogenic gene and haplotype analysis in the single cell level of X-linked severe combined immunodeficiency disease were performed. The protocol can avoid misdiagnosis caused by contamination and ADO, and improve the diagnostic efficiency of PGD.

Objective To explore application and effects of the whole-procedure modular intelligent nursing evaluation system.Methods The whole-procedure modular intelligent nursing evaluation system was designed,and the closed-loop management system was implemented.Nurses' clinical work ability,incidence of nursing adverse events,and satisfaction of discharged patients were compared before and after implementing the whole-procedure modular intelligent nursing evaluation system.Results After application of the whole-procedure modular intelligent nursing evaluation system,nurses' clinical work ability and discharged patients' satisfaction were both improved,incidence of nursing adverse events was significantly lower than before(P＜0.05).Conclusion Application of the whole-procedure modular intelligent nursing evaluation system improved nurses' clinical work ability,reduced incidence of nursing adverse events,and improved discharged patients' satisfaction.

OBJECTIVETo investigate the role of autophagy in MnCl2-induced apoptosis in human bronchial epithelial 16HBE cells.

METHODSCell proliferation was measured by MTT assay. Mitochondrial membrane potential (MMP) and apoptosis were measured by flow cytometry. Autophagic vacuoles were detected by fluorescence microscopy. Cellular levels of apoptosis and autophagy-related proteins were measured by western blotting.

RESULTS16HBE cell proliferation was inhibited by MnCl2 in a dose- and time-dependent manner. MnCl2-induced 16HBE cell growth inhibition was related to MMP depolarization prior to the induction of apoptosis. Our data revealed that MnCl2-induced apoptosis in 16HBE cells was mediated by decreased expression of Bcl-2 and increased levels of cleaved caspase-3. It was observed that when we exposed 16HBE cells to MnCl2 in a dose-dependent manner, the formation of autophagic vacuoles and the levels of LC-3B-II were elevated. RNA interference of LC3B in these MnCl2-exposed cells demonstrated that MMP loss and apoptosis were enhanced. Additionally, the pan-caspase inhibitor Z-VAD-FMK increased the cellular levels of Bcl-2 and decreased apoptosis, but did not affect the cellular levels of LC3B in MnCl2-treated 16HBE cells.

CONCLUSIONMnCl2 dose- and time-dependently inhibits 16HBE cell proliferation and induces MMP loss and apoptosis. Autophagy acts in a protective role against MnCl2-induced apoptosis in 16HBE cells.

Amino Acid Chloromethyl Ketones ; pharmacology ; Apoptosis ; drug effects ; Autophagy ; drug effects ; physiology ; Bronchi ; Cell Line ; Chlorides ; pharmacology ; Down-Regulation ; Epithelial Cells ; drug effects ; Gene Expression Regulation ; drug effects ; Humans ; Manganese Compounds ; pharmacology

OBJECTIVETo investigate the effects of sorafenib on human acute promyelocytic leukemia cell NB4 and its mechanism.

METHODSThe human acute promyelocytic leukemia cell NB4 was treated with different concentrations (0, 1.5, 3, 6 and 12 µmol/L) of sorafenib, the proliferation inhibitory rate of NB4 cells was assayed by MTT, the apoptosis of NB4 was determined with flow-cytomatry after treatment; after extraction of total protein, the Western blot was performed to determine the expressions of apoptosis-relatived molecules Caspase-3, Caspase-8 and MCL-1. The mRNA expressions of Caspase-3, Caspase-8 and MCL-1 were determined by RT-PCR.

RESULTSAs compared with the control group, the proliferation of NB4 significantly decreased after treatment with different concentrations of sorafenib. The sorafenib significantly induced the apopotosis of NB4 cells in time- and dose-dependent manners. Furthermore, sorafenib treatment resulted in the obvious increase of the Caspase-3 and Caspase-8 protein and mRNA expressions, and down-regulated the MCL-1 protein and mRNA expressions in NB4 cells.

CONCLUSIONSorafenib can inhibit proliferation and induce apopotosis of human acute promyelocytic leukemia cell NB4 through the expression of Caspase-3 and Caspase-8, and down-regulation of the expression of MCL-1.

Antineoplastic Agents ; Apoptosis ; Caspase 3 ; Caspase 8 ; Cell Line, Tumor ; Down-Regulation ; Humans ; Leukemia, Promyelocytic, Acute ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; T-Lymphocytes, Helper-Inducer