Objective To investigate the effect of high altitude on peak expiratory flow (PEF) in elderly patients with heart failure and respiratory tract infection and its relationship with inflammatory response. Methods A total of 380 elderly patients over 60 years old with heart failure and respiratory tract infection admitted to our hospital from January 2020 to September 2022 were selected by cluster sampling method as research objects, including 190 long-term residents in high-altitude areas and 190 long-term residents in non-high-altitude areas.Information on current diseases, peak expiratory flow (PEF) levels, and inflammatory status (serum TNF) were collected- α， CRP, PCT and IL-6 levels) and other potential influencing factors; The relevant test indexes were collected at the time of enrollment (baseline) and at the time of discharge after treatment (the shortest hospital stay of 6 days and the longest hospital stay of 21 days); To compare the effects of long-term living at high altitude on PEF level and inflammatory state. The study used spss19 0 statistical software package for analysis. Results In this study, 380 elderly patients over 60 years old with heart failure and respiratory tract infection were enrolled, including 190 long-term residents in high-altitude areas (high-altitude group) and 190 long-term residents in non-high-altitude areas (control group). The mean age of patients in the high altitude group was (66.20±6.56) years old, the proportion of male patients was 53.16%, and the proportion of patients with heart failure duration less than 5 years was 70.00%. The average age of the control group was (66.93±6.77) years old, the proportion of male patients was 53.85%, and the proportion of patients with heart failure duration less than 5 years was 71.79%. The levels of PEF, FEV1 and FVC in 2 groups were higher than the baseline level at discharge (t=2.095, 7.139, 11.047, 14.594, 14.104, 12.250, all P<0.05). And the high altitude group was significantly lower than the control group (t=5.260, 6.912, 6.262, P<0.05). The baseline levels of TNF-α, CRP, PCT and IL-6 in the high altitude group were higher than those in the control group. After treatment, the levels of several inflammation-related factors decreased in both groups, but the high altitude group was still higher than the control group. The expression levels of inflammation-related factors (TNF-α, CRP, IL-6, PCT) in subjects at high altitude were negatively correlated with the levels of lung function related indicators (PEF, FEV1, FVC) (r=-0.453, -0.496, -0.379, -0.563, -0.467, -0.522, -0.497, -0.518, -0.419, -0.416, -0.438, -0.480), and the correlation coefficients were statistically significant (P<0.05). Conclusion High altitude living factors are associated with the decrease of PEF. At the same time, it indirectly aggravates the inflammatory state of patients, and it is more difficult for therapeutic intervention to control the inflammation to the ideal level within the same time, which is worthy of clinical attention.

OBJECTIVE: To explore the clinical application of gastric pharyngeal anastomosis assisted by laparoscope. METHOD: Apply laparoscope in the gastric pharyngeal anastomosis for 4 cases of advanced hypopharyngeal carcinoma and cervical esophageal carcinoma patients. RESULT: Gastric pharyngeal anastomosis assisted by laparoscope were successfully completed in all 4 patients, all patients avoided thoracotomy or laparotomy, one patient occurred pharyngeal fistula, and died six months later. One patient had cervical lymph node metastasis a year and a half later, without treatment again because of economicissue. The remaining two patients were still alive, one patient had survived 3 years and a half after operation, the other had survived 2 years and a half after operation. CONCLUSION Gastric pharyngeal anastomosis assisted by laparoscope is feasible. It can reduce the operation wound, improve the safety of operation and patients' life quality.
Anastomosis, Surgical ; Esophageal Neoplasms ; surgery ; Fistula ; pathology ; Humans ; Hypopharyngeal Neoplasms ; surgery ; Laparoscopy ; Lymphatic Metastasis ; Neck ; Pharynx ; pathology ; surgery ; Survival Rate

OBJECTIVETo explore the influence of GATA-1 on expression of EpoR in bone marrow CD71+ cells of rat model with high altitude polycythemia (HAPC).

METHODSForty-eight male SD rats were randomly divided into normal control and HAPC model group. HAPC model was established at the altitude of 4 300 meters in the natural environment, and verified by bone marrow cell counts and hematological parameters. Myeloid CD71+ cells were separated by the density gradient centrifugation combined with magnetic activated cell sorting. The expression of EpoR on cell membrane was detected by flow cytometry and cell immunofluorescence. The expression changes of GATA-1 and EpoR mRNA and protein were detected by Q-PCR and Western blot, respectively. CD71+ cells were cultured under normoxia and hypoxia, respectively. After transfection for 96 h, the optimal interference sequence GATA-1 shRNA1 was selected. And the mRNA and protein expression level of GATA-1 and EpoR were detected by Q-PCR and Western blot respectively.

RESULTSThe animal model with HAPC was established successfully and comfirmed by the bone marrow cell counting and the hematologic parameters in comparison with that of the normal control. EpoR expression on the myeloid CD71+ cell membrane in HAPC group was significantly higher than that in normal control (P<0.05). The expression of GATA-1 and EpoR in myeloid CD71+ cells of HAPC group was higher than that in control group (P<0.05). The mRNA and protein expression of GATA-1 and EpoR in two groups positively correlated (control group, r=0.929, P<0.01, r=0.802, P<0.05; HAPC group, r=0.822, P<0.05, r=0.839, P<0.01). However, the mRNA and protein expression of EpoR at normoxia and hypoxia was significantly lower than that in negative control group after interfernce with GATA-1 shRNA1 for 96 h (P<0.05). And the expression of GATA-1 and EpoR under hypoxia was higher than that in normoxia.

CONCLUSIONThe effect of GATA-1 on EpoR expression may be correlated with the pathogenesis of HAPC.

Altitude ; Animals ; Antigens, CD ; metabolism ; Bone Marrow Cells ; metabolism ; Cell Separation ; Disease Models, Animal ; Flow Cytometry ; GATA1 Transcription Factor ; metabolism ; Male ; Polycythemia ; metabolism ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Erythropoietin ; metabolism ; Receptors, Transferrin ; metabolism

OBJECTIVETo study the efficacy and safety of anti-human thymocyte immunoglobulin(ATG-F) combined with cyclosporin A(CsA) on patients with severe aplastic anemia (SSA), so as to provide support for clinical work.

METHODSFrom January 2010 to December 2015, 78 patients with SAA admitted in our hospital were divided into 2 groups: ATG-F+CsA group(40 cases) and ATG-F group(38 cases). After treatment for 6 months, the effective rate, side reaction rate and time of effect initiation were compared between 2 groups. The follow-up results were compared between 2 groups.

RESULTSThe effective rate and side reaction rate in ATG-F+CsA group were 100.00% and 32.50% respectively, those in ATG-F group were 94.74% and 44.74% respectively and without statistical significant difference(P>0.05). In ATG-F+CsA group, the time of effect initiation in cured patients, remission and obvious inprovement were (44.9±15.4) d, (68.8±15.9) d and (85.4±17.6) d; in ATG-F group, patients with those were (59.6±11.5) d, (94.7±17.8) d and (119.8±21.4) d respectively, the difference showed statistical significance(P<0.05). The follow-up results were not statistically significantly different between 2 groups(P>0.05).

CONCLUSIONATG-F combined with CsA can shorten the time of effect initiation, and demonstrates reliable safety.

OBJECTIVETo investigate the therapeutic efficacy of rituximab combined with methotrexate on patients with primary central nervous system lymphoma.

METHODSFifty eight patients with central nervous system lymphoma treated in our hospital from February 2008 to September 2011 years were randomly divided into the observation group and the control group. The control group was treated with methotrexate combined with whole brain radiotherapy; the observation group was treated by rituximab combined with methotrexate. The curative efficacy, adverse effects, life quality, and the 1 and 3 year survival rate after 2 cycles of treatment were compared between 2 groups.

RESULTSThe total effective rate of observation group was 82.76%, which significantly higher than 58.62% of the control group (P < 0.05). In observation group, the incidences of anemia, liver damage, gastrointestinal side effect and oral ulcer were significantly lower than that in control group, respectively (P < 0.05). The physiological function, physical function, health status, social and emotional function in the observation group were significantly higher than those in the control group (P < 0.05), 1 and 3 years survival rates in the observation group were 86.21% and 62.07%, significantly higher than 58.62% and 31.03% in the control group (P < 0.05).

CONCLUSIONTargeted therapy combined with chemotherapy for the primary central nervous system lymphoma can improve the patients' outcomes, reduce adverse effects, and improve the quality of life and survival rate.

Central Nervous System Neoplasms ; drug therapy ; Humans ; Lymphoma, Non-Hodgkin ; drug therapy ; Methotrexate ; therapeutic use ; Quality of Life ; Rituximab ; therapeutic use ; Survival Rate ; Treatment Outcome

Chronic hypoxic lung diseases are major causes of disability and mortality worldwide, which are typically aggravated by hypoxic pulmonary hypertension.The pathogenesis of hypoxic pulmonary hypertension is complex, and its mechanism has not been fully elucidated.The previous studies have shown abnormally elevated levels of free Ca + in the cytoplasm of pulmonary artery smooth muscle cells to be the predominant drivers of pulmonary hypertension , causing continuous contraction and remodeling of the pulmonary vessels.This article briefly summarizes the mechanism of hypoxia-induced imbalance in calcium homeostasis in pulmonary artery smooth muscle cells, together with its related drug research, based on the existing literature.Hypoxia induces an imbalance in calcium homeostasis in pulmonary artery smooth muscle cells by regulating hypoxia-inducible factor-1, K+ , store-operated calcium channel, receptor-operated calcium channel, the Ca +-sensing myosin contractile mechanism by binding to calmodulin, leading to pulmonary vasoconstriction.Ca + can also activate PKC/ MAPKs and PI3K/Akt/mTOR pathways, leading to pulmonary vascular remodeling.

UNLABELLEDObjective： To study the effect of PD98059, a specific inhibitor of Ras/Raf/MEK/ERK signaling pathway, on the proliferation and apoptisis of bone marrow CD71(+), CD235a(+) nucleated erythrocytes in patients with high altitude polycythemia (HAPC) and the pathogenesis of HAPC.

METHODSThe CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients and controls (patients with simple obsolete stracture) were sorted by using the immunemagnetic beads, then were added with 5, 10, 20 µmol/L of PD98059 and DMSO (as control) and were cultured for 72 h under hypoxia. The cell apoptosis was detected by flow cytometry with Annexin V and PI double staining, the cell proliferation was detected by CCK8 method, at same time the erythroid colong-formation ability of bone marrow mononuclear cells (BMMNC) treated with 5, 10, 20 µmol/L of PD98059 and DMSO was observed.

RESULTSWith the increase of PD98059 concentration, the apoptosis rate of bone marrow CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients was enhanced (r=0.807,P<0.01), while the proliferation rate of CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients dereased (r=0.502,P<0.01). The erythroid colong-formation ability of BMMNC in HAPC patients decreased with the increase of PD98059 concentration (r=0.504,P<0.01). There were statistic differences among different groups at 7 and 14 d.

CONCLUSIONThe MEK specific inhibitor PD98059 can inhibit the proliferation and promote the apoptosis of CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients, then inhibit the excessive accumulation of erythrocytes.

Altitude Sickness ; Apoptosis ; Bone Marrow ; Bone Marrow Cells ; Cell Proliferation ; Erythroblasts ; Erythrocyte Count ; Erythrocytes ; Flavonoids ; Flow Cytometry ; Glycophorin ; Humans

The technology of lipid-drug conjugates is developed on the basis of prodrug principle, which overcomes some drawbacks of drugs via increasing the lipophilicity of hydrophilic or poorly soluble drugs to promote the absorption of drugs and enhance the curative effect. This article sums up the research progress of lipid-drug conjugates from the chemical synthesis methods of conjugates, the types of conjugates, the influence on biological activity of drugs, the application in nanoparticles for drug delivery and the mechanism of absorption and degradation.

Objective:To observe the effect of syndrome differentiation and treatment with Wandaitang on symptoms, quality of life and function of immunologic after operation of endometrial carcinoma (EC), in order to discuss the mechanism of action according to regulation of microenvironment of EC. Method:The 109 patients were divided into control group (54 cases) and observation group (55 cases) by random number table. Patients in control group got radiotherapy and/or chemotherapy according to different stages after operation. Patients in observation group were additionally given syndrome differentiation and treatment with Wandaitang, 1 dose/day. And a course of treatment was 3 months. Before and after treatment, symptoms, sign, functional assessment of cancer therapy-general (FACT-G) were scored. And levels of T lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺), natural killer cell (NK), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), insulin-like growth factor-1(IGF-1), interleukin-17 (IL-17) and IL-10 were detected. Result:After treatment, the scores of symptoms, signs and total scores of the patients in the observation group were lower than the control group (P<0.01).The scores of each dimension and total score of FACT-G scale in the observation group were higher than those in the control group(P<0.01). After treatment, NK, CD3 ⁺, CD4 ⁺ and CD4 ⁺/CD8 ⁺ in the observation group were higher than those in the control group(P<0.01),lower than the control group(P<0.01). After treatment, the serum levels of VEGF, TGF-β, IGF-1, IL-17 and IL-10 in the observation group were lower than those in the control group. Conclusion:Wandaitang can ameliorate clinical symptoms, improve quality of life of patients and immune function of organism, regulate multiple cytokines, change the tumor microenvironment of endometrial carcinoma.

OBJECTIVETo investigate the effect of ERK1 / 2 signaling pathway inhibitor PD98059 on Ras, Raf, MEK, ERK1, ERK2 expression in order to explore a new way for basic research and clinical treatment of the chronic mountain sickness(CMS).

METHODSSixteen CMS patients were selected, the bone marrow was collected for isolation of monomuclear cells (MNC), the cells were sorted by using CD71 and CD235a antibody magnetic beads, then positive cells were diveded into 5 groups: blank control, DMSO and PD98059 5, 10 and 20 µmol/L, and were cultured in hypoxid condition for 72 hours. The Ras-GTP levels in supernatant was detected by ELISA, the RT-PCR was used to determine the expression of BRaf, MEK, ERK1, ERK2 mRNA in nucleated red blood cells, and the Western blot method was used to detect expression of BRaf, MEK, ERK1, ERK2 protein.

RESULTSPD98059 had no effect on the level of Ras-GTP in each groups. Compared with the blank control group, the expression levels of BRaf, MEK mRNA in DMSO group were not statistically significant (P values were 0.826, 0.298). Compared with the PD98059 20 mol/L group, the expression level of ERK1/2 mRNA was statistically significant (P=0.001, 0.002). Compared with the blank control group, expression levels of p-BRaf, p-MEK protein in DMSO group were not statistically significant (P=0.370, 0.351). Compared with the PD98059 20 mol/L group, the difference of p-ERK1/2 protein level in other 4 groups were statistically significant (P values were <0.001, 0.007).

CONCLUSIONPD98059 can up-regulate the expressions of ERK1/2 miRNA and p-ERK1/2 protein in bone marrow nucleated red blood cells, the Ras / Raf / MEK / ERK 1/2 pathway is the main signal transduction pathway in regulating bone marrow nucleated red blood cells, suggesting that Ras/Raf /MEK /ERK 1/2 pathway may be involved in the pathogenesis of chronic mountain sickness process.