Objective To evaluate the current situation of disease control in middle-aged and elderly patients with chronic obstructive pulmonary disease (COPD) and analyze the relationship with disease cognition. Methods Among the 360 middle-aged and elderly COPD patients diagnosed and treated in our hospital from January 2022 to June 2024 were retrospectively selected as research subjects, and the COPD Assessment Test Questionnaire (CAT), COPD Patient Knowledge Questionnaire (BCKQ) and the hampion Health Belief Model Scale were used to evaluate disease control, disease cognition and health beliefs in COPD patients. The Pearson chi-square test was used to analyze the relationship between disease control level and disease cognition and health beliefs in older patients with COPD. Results A total of 360 middle-aged and elderly COPD patients, 112 were in the complete control group, 189 were in the partial control group, and 59 were in the uncontrolled group, the disease control rate was 83.61%. The differences in disease cognitive scores, severity cognition, susceptibility cognition, disorder cognition, benefit cognition, health motivation, self-efficacy score and total health belief scores in middle-aged and elderly COPD patients with different disease control conditions are statistically significant. The scores of the complete control group were higher than those of partial control group and uncontrolled group, and the scores of partial control group were higher than those of the uncontrolled group (P <0.05). The disease control level of middle-aged and elderly patients with COPD is positively correlated with disease cognitive level and health belief in all dimensions. The higher the disease control level, the higher the disease cognitive level and health belief in the patient . Conclusions Middle-aged and elderly COPD patients still have insufficient awareness of the disease, and the level of disease control needs to be improved. There is a significant correlation between disease cognition, health beliefs and the level of disease control, and the improved cognitive level may help to improve the disease management and control effect. For middle-aged and elderly COPD patients, the community can provide health education courses, personalized health guidance and self-management training to enhance their awareness of diseases, so as to improve the long-term management of COPD and the quality of life of patients.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Objective:To screen plasma metabolic markers in patients with unexplained recurrent spontaneous abortion (URSA) by non-target metabolomics approach.Methods:From September 2022 to May 2023, the plasma of 23 URSA pregnant women with threatened abortion who visited the outpatient clinic of Gansu Provincial Maternity and Child-care Hospital in the first trimester (URSA group) was collected, and the plasma of 22 healthy pregnant women in the first trimester who underwent prenatal examination during the same period (normal control group) was collected. Plasma metabolomics was analyzed by ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS), fold change analysis, principal component analysis and partial least square discriminant analysis were applied to screen for differential metabolites, and the metabolites and their pathways associated with URSA were screened using receiver operating characteristic (ROC) curve and pathway enrichment analysis.Results:There were no significant differences in age, body mass index and gestational weeks between URSA and normal control group(all P<0.05). Metabolomics analysis using UPLC-MS showed that a total of 526 metabolites were detected from plasma, of which 33 were found to be differential metabolites associated with URSA based on the screening standards. Six potential metabolites with large area under the curve (AUC) were identified by ROC curve analysis, including phosphatidylethanolamine (AUC=0.972, 95% CI: 0.920-1.000), santene hydrate (AUC=0.902, 95% CI: 0.786-0.982), L-leucine (AUC=0.884, 95% CI: 0.772-0.960), cembrene (AUC=0.881, 95% CI: 0.758-0.956), caffeine (AUC=0.875, 95% CI: 0.756-0.962), and 4-hydroxybenzoic acid propyl ester (AUC=0.864, 95% CI: 0.732-0.946). The AUC for the combined diagnosis of URSA by the six metabolites was 0.983 (95% CI: 0.929-1.000). Pathway enrichment analysis of the differential metabolites showed that the pathogenesis of URSA was associated with a variety of metabolic pathways including caffeine metabolism, glycerophospholipid metabolism, and unsaturated fatty acid biosynthesis. Conclusion:The plasma metabolic profiles of pregnant women with normal pregnancies versus URSA differ in early pregnancy, and six potential metabolites such as phosphatidylethanolamine, santene hydrate, L-leucine, cembrene, caffeine, 4-hydroxybenzoic acid propyl ester, and their metabolic pathways may be involved in the pathogenesis of URSA.

Objective:To explore the role of c-Jun N-terminal kinase (JNK) /c-Jun signaling pathway mediated by endoplasmic reticulum stress in triptolide-induced apoptosis of melanoma A375 cells.Methods:Nude mice were subcutaneously inoculated with melanoma A375 cells on the back to establish the animal model of melanoma. Tumor formation could be observed at approximately 3 weeks after inoculation, and then the mice were divided into 4 groups (4 mice in each group) : control group (injected with sodium chloride physiological solution via the tail vein), 0.1-, 0.2-, and 0.4-mg/kg triptolide groups (injected with 0.1, 0.2, and 0.4 mg/kg triptolide via the tail vein, respectively). Injections were performed twice a week. After 3 weeks of injections, tumors were resected, and their size and weight were measured. The apoptosis levels of tumor xenografts were detected by the terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay. qPCR was conducted to determine the mRNA expression of inositol-requiring enzyme 1 (IRE1), JNK, and c-Jun, and Western blot analysis to determine the protein expression of IRE1, JNK, c-Jun, phosphorylated-JNK (p-JNK), and phosphorylated-c-Jun (p-c-Jun). Comparisons among multiple groups were performed using one-way analysis of variance, and multiple comparisons were performed using Dunnett's test.Results:Significant differences were observed in the tumor mass, volume and tumor suppression rate among the control group, 0.1-, 0.2-, and 0.4-mg/kg triptolide groups (all P < 0.05) ; all the triptolide groups showed significantly decreased tumor masses and volumes (all P < 0.05), but significantly increased tumor suppression rates compared with the control group (all P < 0.05). The tumor apoptosis index significantly differed among the control group, 0.1-, 0.2-, and 0.4-mg/kg triptolide groups (7.67% ± 1.15%, 9.67% ± 3.21%, 62.00% ± 6.08%, and 85.67% ± 5.51%, respectively; F = 305.91, P < 0.001), and the 0.2- and 0.4-mg/kg triptolide groups showed significantly increased tumor apoptosis indices compared with the control group ( t = 17.56, 27.72, respectively, both P < 0.05). qPCR and Western blot analysis revealed significant differences in the mRNA expression of IRE1, JNK, and c-Jun among the control group, 0.1-, 0.2-, and 0.4-mg/kg triptolide groups ( F = 112.23, 27.51, 112.37, respectively, all P < 0.05), as well as in the relative protein expression levels of IRE1, JNK, c-Jun, p-JNK, and p-c-Jun among the above 4 groups (all P < 0.05). Additionally, the 0.4-mg/kg triptolide group showed significantly increased mRNA and protein expression of IRE1, JNK and c-Jun (including p-JNK, p-c-Jun) compared with the control group (all P < 0.05). The mRNA and protein expression levels of IRE1, JNK, and c-Jun in the tumor tissues tended to increase with the rise in drug concentrations, and the protein expression levels of p-JNK and p-c-Jun showed the same trend. Conclusion:Triptolide could activate the JNK/c-Jun signaling pathway mediated by the endoplasmic reticulum stress, and then induce apoptosis of melanoma A375 cells in mice.

Objective To explore the effect of controlled low central venous pressure(CLCVP)on venous congestion and postoperative acute kidney injury(AKI)in cardiac surgery under cardiopulmonary bypass(CPB).Methods A total of 137 patients scheduled for elective cardiac surgery under general anes-thesia with CPB were selected,including 73 males and 64 females,aged 18 to 70 years,with a BMI of 20 to 28 kg/m2,and ASA physical status Ⅱ or Ⅲ.The patients were randomly assigned into two groups:the controlled low central venous pressure group(group CL,n=68)and the control group(group C,n=69).In group CL,CLCVP was applied by pumping nitroglycerin to reduce CVP to below 10 mmHg after 20 minutes of CPB cessation until the end of surgery.If necessary,norepinephrine was applied to maintain MAP≥65 mmHg.Patients in group C received standardized anesthesia management.Urine samples were collected before anesthesia induction and 12 hours postoperatively to detect the concentration of kidney injury molecule-1(KIM-1).Urine samples were also collected before anesthesia induction and 2 hours postopera-tively to detect the concentration of neutrophil gelatinase-associated lipocalin(NGAL).Cumulative time a-bove 10,12,16,and 20 mmHg and time-weighted average CVP were used to assess venous congestion.The occurrence of postoperative AKI,stage 2 or above AKI,renal replacement therapy(CRRT),postoperative low cardiac output syndrome(LCOS),acute kidney injury following cardiac surgery(AKICS)score when arriving in ICU,in-hospital mortality,ICU stay,and postoperative hospital stay were recorded.Results Compared with group C,the cumulative time of CVP above 10,12,16,and 20 mmHg after CPB in group CL was significantly shorter,and the time-weighted average CVP was significantly lower(P＜0.05).AKI occurred in 9 patients(13.2%)in group CL and 15 patients(21.7%)in group C postoperatively,and there was no significant difference between the two groups.One case(1.5%)of stage 2 or above AKI oc-curred in group CL and 2 patients(2.9%)in group C,with one patient in group C requiring CRRT.Com-pared with group C,the concentrations of KIM-1 at 12 hours postoperatively and NGAL at 2 hours postoper-atively were significantly lower in group CL(P＜0.05).There were no statistically significant differences between the two groups in LCOS,AKICS score,in-hospital mortality,ICU stay,and postoperative hospital stay.Conclusion Controlled low central venous pressure in cardiac surgery under cardiopulmonary bypass can reduce venous congestion and decrease the occurrence of postoperative renal injury,thereby exerting a certain renal protective effect.

Objective:To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment.Methods:Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella.Results:Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced ( P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella ( P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice ( P<0.05). Conclusions:Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.

Objective:We genetically modified our non-replicating vaccinia virus NTV to improve its immunogenicity.Methods:We constructed NTV-modified strain NTV-ΔF1L-C7L by homologous recombination of vaccinia virus based on CRISPR-Cas9 technology by inserting the C7L gene while deleting the F1L gene. The recombinant virus NTV-ΔF1L-C7L was then immunized with 10 7 PFU in BALB/c mice, and the levels of humoral and cellular immunity induced by NTV-ΔF1L-C7L were detected by ELISA and ELISpot method, respectively, and the levels of neutralizing antibodies were determined by the phage-reduced neutralization assay. Results:The PCR and western- blot identification proved that the F1L gene of the constructed NTV-modified strain NTV-ΔF1L-C7L was missing, while the C7L gene was inserted back in the region, and the C7L gene could be expressed normally, indicating that the recombinant virus was constructed correctly. After immunization of mice with NTV-ΔF1L-C7L, ELISA result showed that the recombinant virus NTV-ΔF1L-C7L induced a higher level of IgG antibody than NTV; ELISpot result also showed that the recombinant virus was able to induce a higher level of IFN-γ; and the result of plaque reduction neutralization test showed that the recombinant virus was able to induce a higher level of IFN-γ antibody than that of NTV.Conclusions:We correctly constructed the NTV gene-modified strain NTV-ΔF1L-C7L, which induced stronger humoral and cellular immunity compared with NTV, and provided reference data for the research and development of replacement products for smallpox or monkeypox vaccines.

Objective:To discuss the differences in eosinophil(EOS)infiltration in cervical tissue and its relationship with cervical-related diseases,and to clarify the effect of EOS on the occurrence and development of cervical intraepithelial neoplasia(CIN)and cervical cancer.Methods:The clinical data of 256 patients with cervical diseases were collected and divided into cervical cancer group(n=46,including 26 cases of squamous cell carcinoma,15 cases of adenocarcinoma,and 5 cases of adenosquamous carcinoma),chronic cervicitis group(n=50),CIN stage Ⅰ group(n=50),CIN stage Ⅱ group(n=50),CIN stage Ⅲ group(n=30),and normal group(adjacent normal cervical tissue,n=30)based on their conditions.Colposcopy was used to observe the morphology of cervical tissue of the patients in various groups;thin-layer liquid-based cytology test(TCT)was used to observe the morphology of the cervical exfoliated cells in various groups;hybrid capture-chemiluminescence method was used to detect the human papillomavirus(HPV)infection in cervical tissue of the patients in various groups;HE staining was used to observe the pathomorphology of cervical tissue of the patients in various groups;Congo red staining was used to detect the numbers of EOS infiltration in cervical tissue of the patients in various groups;Pearson correlation analysis was used to analyze the correlation between the number of EOS infiltration and the malignancy degree of cervical cancer.Results:The cervical surface of the patients in normal group was smooth and pink,with uniformly distributed capillaries;the cervical surface of the patients in chronic cervicitis group showed red inflammatory changes,with some accompanied by Nabothian cysts and varying degrees of erosion and ulcers;the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups showed epithelial ulcers,thickening,and irregular morphology,with mosaic and punctate vessels;the cervical surface of the patients in cervical cancer group showed raised areas with neoplasms and necrotic ulcers,and they were fragile and prone to bleeding.After acetic acid staining,no obvious changes of the patients in normal group were observed.The cervix of the patients in chronic cervicitis group showed slight white changes that lasted for a short time;in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,irregular thin acetowhite epithelium with map-like borders was observed,with increasingly acetowhite reactions and larger areas as the stages advanced.The cervix of the patients in cervical cancer group showed thick acetowhite epithelium that lasted longer,with rigid and clear contours.After iodine staining,the cervix of the patients in normal group was brown,with uniform coloration;the cervix of the patients in chronic cervicitis group showed poor coloration in inflammatory lesion areas;the cervix of the patients in CIN stage Ⅰ group showed iodine coloration in metaplastic areas,while the cervix of the patients in CIN stage Ⅲ group showed poor coloration in larger lesion areas;the cervix of the patients in cervical cancer group showed irregular surfaces with cauliflower-like growth and no coloration after iodine staining,appearing orange-yellow or mustard yellow.The TCT observation results showed there were no heteromorphic cells and few inflammatory cells in cervical exfoliated cells of the patients in infiltration in normal group;there were numerous neutrophils and EOS in exfoliated cervical cells without heteromorphic cells in chronic cervicitis group.The heteromorphic binucleated cells with high nuclear-cytoplasmic ratios and deeply stained nuclei were observed in cervical exfoliated cells of the patients in CIN stage Ⅰ and CIN stage Ⅱ groups.More heteromorphic cells with high nuclear-cytoplasmic ratios and irregular nuclear membranes were showed in cervical exfoliated cells of the patients in CIN stage Ⅲ group.The cervical exfoliated cells of the patients in cervical cancer group showed large and prominent nucleoli,clustering into syncytial changes.Compared with normal group,the atypial of cervical exfoliated cells in CIN stage Ⅰ,CIN stage Ⅱ,CIN stage Ⅲ,and cervical cancer groups was increased.The hybrid capture-chemiluminescence results showed that compared with normal and chronic cervicitis groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in cervical cancer group were increased(P<0.05).The HE staining results showed normal cell morphology and structure in normal group,with infiltration of inflammation cells such as neutrophils,monocytes,macrophages,EOS,and lymphocytes;in chronic cervicitis group,the infiltration of inflammatory cells was increased;in CIN group,the cervical cells showed slightly larger nucleoli and heteromorphic cells,with inflammatory cells mainly distributing around the hetermomorphic cells;in cervical cancer group,the cervical cells showed large and deeply stained nucleoli with significant atypia,and the infiltration of inflammatory cells around the cancer cells was increased.Compared with normal group,the numbers of inflammatory cells and EOS infiltration in cervical tissue of the patients in chronic cervicitis group were increased(P<0.05),and the numbers of inflammatory cells and EOS infiltration of the patients in CIN group were increased(P<0.05);compared with chronic cervicitis group,the number of inflammatory cells and EOS infiltration of the patients in CIN group were decreased(P<0.05);compared with chronic cervicitis group and CIN group,the numbers of inflammatory cells and EOS infiltration of the patients in cervical cancer group were increased(P<0.05).The EOS in cervical cancer tissue was mainly distributed around the cancer nests;compared with CIN stage Ⅰ group,the numbers of EOS infiltration in CIN stage Ⅱ and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅱ group,the number of EOS infiltration in CIN stage Ⅲ group was increased(P<0.05).The higher the malignancy degree of the tumor,the more EOS infiltration was observed,and the number of EOS infiltration was positively correlated with the invasion depth of cervical cancer(r=0.533 0,P<0.01).Conclusion:HPV infection and EOS infiltration play a role in promoting the and occurrence development of cervical precancerous lesions and cervical cancer.

Objective To create the new type critical illness score scale based on logistic regression pre-diction model,and to evaluate its predictive value for the patient transferring to intensive care unit (ICU) and death.Methods The clinical data in 1000 patients were retrospectively collected from the HIS system of this hospital from October 2022 to October 2023.The new critical illness score scale was created based on the model in predicting the ICU transfer rate created by the previous studies.The modified early warning score (MEWS) and acute physiology and chronic health evaluation Ⅱ (APCHEⅡ) score served as reference respec-tively,the predictive value of the new type critical illness score scale for patient transferring to ICU and death was evaluated by using the receiver operating characteristic (ROC) curve and area under curve (AUC).Results The ICU transfer rate of the patients was 29.8％,and the mortality rate was 8.10％.The new type critical illness score scale,MEWS and APCHEⅡ scores of the patients who were transferred to ICU or died were significant-ly higher than those of the patients who were not transferred to ICU or died (P<0.05).The predictive value of the new critical illness scale,MEWS,and APCHEⅡ scores for ICU transfer was high (P<0.05).AUC was 0.917,0.922 and 0.934 respectively,the sensitivity was 82.26％,84.22％ and 90.57％ respectively,the speci-ficity was 80.36％,73.50％ and 83.45％ respectively and the Youden index was 62.62％,57.72％ and 74.02％,respectively.The predictive value of the new type critical illness score scale,MEWS and APCHEⅡ scores for the death was high (P<0.05).AUC was 0.924,0.914 and 0.933 respectively,the sensitivity was 93.48％,86.38％ and 84.67％ respectively,the specificity was 73.46％,79.38％ and 88.69％ respectively,and the Youden index was 66.94％,65.76％ and 73.36％ respectively.Conclusion The predictive value of the new type critical illness score scale for the patients transferring to ICU and death is basically consistent with that of the traditional scales,which could serve as a new evaluation tool for ICU patients.

Objective:To develop the Nutrition Impact Symptom Scale for Colorectal Cancer Patients.Methods:Guided by the theory of unpleasant symptoms, the initial draft of the scale was formed through literature research, expert consultation, and small sample pre-survey. From March to May 2023, convenience sampling was used to select 127 colorectal cancer patients who visited Jiangsu Cancer Hospital as the research subject for item analysis and reliability and validity testing of the scale.Results:The final scale consisted of five dimensions and a total of 17 items. The content validity index of the scale was from 0.83 to 1.00, with an average content validity index of 0.97. Exploratory factor analysis extracted five common factors, and the cumulative variance contribution rate was 61.622%. The total Cronbach's α coefficient of the scale was 0.708, and the coefficients for each dimension were 0.762, 0.642, 0.625, 0.510, and 0.644, respectively. The half reliability coefficient of the scale was 0.824.Conclusions:The development process of the Nutrition Impact Symptom Scale for Colorectal Cancer Patients is scientific, with good reliability and validity, and can be used to evaluate the nutrition impact symptom of colorectal cancer patients.