Objective To investigate the changes and diagnostic value of serum hypoxia inducible factor 1 subunit alpha(HIF-1α)and Toll-like receptor 4(TLR4)levels in patients with chronic obstructive pulmonary disease(COPD)complicated with pulmonary Aspergillosis infection.Methods A total of 240 COPD patients who visited Xi'an Qinhuang Hospital(hereinafter referred to as the hospital)from December 2020 to Decem-ber 2023 were selected as the study subjects in the study,and another 218 volunteers who underwent physical examinations at the hospital were selected as the control group.The COPD patients were separated into an in-fected group(124 cases)and an uninfected group(116 cases)based on whether they had pulmonary Aspergil-losis infection.Enzyme-linked immunosorbent assay was applied to detect the levels of HIF-1α and TLR4 in patients.Fully automated biochemical analyzer was applied to detect lactate dehydrogenase(LDH)and albu-min(ALB)levels.Multivariate Logistic regression was applied to analyze the influencing factors of infection in COPD patients.Pearson correlation was applied to analyze the correlation between HIF-1α and TLR4 levels in the infected group.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic val-ue of HIF-1α and TLR4 levels for the occurrence of infection in COPD patients.Results Compared with the control group,the COPD group showed an increase in HIF-1α and TLR4 levels(P＜0.05).Compared with the uninfected group,the proportion of dyspnea,antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,mechanical ventilation procedures,the longer glucocorticosteroid(GC)use time,and levels of LDH,HIF-1α,TLR4 in the infected group were higher(P＜0.05),while the level of ALB was lower(P＜0.05).The types of antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,the duration of GC use,and elevat-ed levels of LDH,HIF-1α,and TLR4 were independent risk factors for infection in COPD patients(P＜0.05),while elevated level of ALB was an independent protective factor for infection in COPD patients(P＜0.05).The levels of HIF-1α and TLR4 in the infected group were positively correlated(r=0.453,P＜0.001).The area under the curve(AUC)of HIF-1α and TLR4 in diagnosing infection in COPD patients alone was 0.816 and 0.813,and the AUC of their combined diagnosis was 0.930,which was better than their indi-vidual diagnoses(Zcombination-HIF-1α=4.923,Z combination-TLR4=5.192,P＜0.001,P＜0.001).Conclusion The levels of HIF-1α and TLR4 increase in COPD patients,and further increase after infection with pulmonary Aspergil-lus.They are independent risk factors for infection in patients,and the two are positively correlated.The combined di-agnosis of pulmonary aspergillosis has certain value and provides a theoretical basis for clinical diagnosis.

Objective To investigate the application value of bronchoalveolar lavage fluid(BALF)met-agenomic next-generation sequencing(mNGS)in elderly patients with severe pneumonia.Methods A total of 48 elderly patients with severe pneumonia admitted to the intensive care unit from January to August 2024 were selected and randomly divided into an observation group and a control group,with 24 patients in each group.BALF samples were collected within 24 hours of ICU admission from both groups,with lavage per-formed at the most radiologically evident lesion site.The control group underwent traditional culture at the hospital,while the observation group had one specimen sent for mNGS testing and another specimen subjected to traditional culture at the hospital.Comparison of detection results between mNGS and traditional culture in the observation group,pathogen distribution,infection markers(on days 4 and 7 of ICU admission),and prog-nostic outcomes were compared between the groups.Results The observation group showed higher positive detection rates and higher rates of detecting ≥2 pathogens by mNGS compared to both traditional culture in the same group and the control group(P＜0.05).Excluding Acinetobacter baumannii,Candida albicans,Can-dida glabrata,and Raoultella planticola,the observation group detected higher quantities of fungi,viruses,and rare pathogens than the control group.On days 4 and 7 of ICU admission,the observation group had signifi-cantly lower body temperature,white blood cell count,C reactive protein,and procalcitonin levels compared to the control group(P＜0.05).The observation group also demonstrated shorter ICU stays,reduced mechanical ventilation duration,and total lower hospitalization costs than the control group(P＜0.05).Conclusion BALF mNGS facilitates early identification of mixed and rare pathogens,improves detection rates,broadens microbial coverage,and shortens testing time.

Objective To evaluate the postoperative survival quality in the patients with heart valve re-placement (HVR) in Three Gorges Reservoir area,and to analyze its main influencing factors.Methods A to-tal of 343 valvular heart disease patients from Three Gorges Reservoir area who received HVR treatment for the first time in this hospital from January 2019 to December 2021 were selected by the convenience sampling method.The general data questionnaire and the MOS 36-item short form health survey (SF-36) were adopted to conduct the survey.The main influencing factors affecting the survival quality were analyzed.Results Af-ter HVR,the physical components summary (PCS) score of SF-36 was 238.0±73.6,and the mental compo-nents summary (MCS) score was 254.8±83.6,and the scores in each dimension were significantly lower than those of the Chinese norm (P<0.05).The multiple stepwise linear regression analysis results showed that the age,gender,place of residence,education level,postoperative time,complications and readmission were the influencing factors of PCS and MCS scores (P<0.05).Conclusion The survival quality of the patients af-ter HVR is different from that of healthy population.The targeted intervention could be carried out according to the influencing factors of the survival quality of the patients,so as to improve their survival quality.

Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

Objective:To investigate the in vitro inhibitory activity of a novel class Ⅰ and Ⅱb selective histone deacetylase (HDAC) inhibitor, purinostat mesylate (PM) , in diffuse large B-cell lymphoma and its mechanism.Methods:The 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide method was used to detect the effect of PM on cell proliferation. The effects of PM on cell cycle and apoptosis were detected by flow cytometry. The acetylation levels of HDAC substrate, cell cycle protein, apoptosis-related protein, and oncogene protein expression were detected by Western blot.Results:PM significantly inhibited the proliferation of lymphoma SUDHL-4 and SUDHL-6 cells and increased the acetylation levels of HDAC substrates H3, H4, and α-tubulin. In cell cycle experiments, PM induced G 0/G 1 phase arrest in SUDHL-4 and SUDHL-6 cells. Western blot experiment showed that PM could significantly downregulate the expression of cyclin-dependent kinases Cdk2, Cdk4, Cdk6, cyclin D1, and cyclin E and upregulate the expression of CDK inhibitor protein p21. In the apoptosis experiment, PM could induce the apoptosis of SUDHL-4 and SUDHL-6 cells. Western blot experiment demonstrated that PM promoted endogenous apoptosis by activating caspase-3 kinase and affecting antiapoptotic protein Bcl-2. In addition, PM could downregulate the expression of oncogene marker proteins MYC, IKZF1, and IKZF3. Conclusion:PM has an efficient biological activity in vitro for diffuse large B-cell lymphoma, including double-hit lymphoma, and provides valuable experimental evidence for PM in clinical treatment.

Objective To investigate the prediction of axillary lymph node metastasis in patients with early breast cancer by sentinel lymph node biopsy (SLNB) combined with preoperative ultrasound.Methods From Jun 2014 to Oct 2018,340 patients with early breast cancer were enrolled in the 5th Department of General Surgery of Second Hospital of Lanzhou University.113 cases were grouped into ultrasound examing,75 patients in the SLNB,and 152 patients in the SLNB combined with preoperative ultrasound.Using the results of axillary lymph node dissection as gold standard,the 3 groups were compared.Results The sensitivity of SLNB,ultrasound and SLNB combined with ultrasound for suspicious axillary lymph node biopsy were 90.1％,85.7％,and 96.4％,respectively.The specificity was 84.0％,76.3％,and 100％,and the accuracy was 91.6％,83.0％,and 97.4％,respectively.The false negative rates were 8.6％,14.3％,and 3.6％,respectively.Conclusion Preoperative ultrasound diagnosis of axillary lymph node status combined with sentinel lymph node biopsy can significantly improve the diagnosis rate of axillary lymph node metastasis in early breast cancer.

Objective To analyze the risk factors of acute kidney injury after orthotropic liver transplantation for adult benign end-stage liver disease.Methods A retrospective analysis was conducted in 30 recipients (18 males,12 females,aged 23-68 years,ASA grade Ⅲ or Ⅳ) who underwent orthotropic liver transplantation for benign end-stage liver disease at Tongji Hospital from May,2014 to December,2014.Both demographic characteristics and perioperative parameters were collected,including general condition,surgery and anesthesia factors and intraoperative salvage autotransfusion or not.Perioperative laboratory findings related to renal function including urine volume,serum creatinine (Scr) and urea nitrogen (BUN) were collected,too.All variables tested in the univariate analysis with a P<0.10 were included in a multiple logistic regression analysis.Results There were less intraoperative salvage autotransfusion,more platelet transfusion and a higher using rate of vasopressors in the AKI group after surgery than those did not.Patients who received intraoperative salvage autotransfusion had 0.058 time odds (95%CI 0.005-0.649) of AKI than those did not;patients who required platelet transfusion had 10.706 times higher odds (95%CI 1.212-94.963) of AKI than those did not.Conclusion It is likely that intraoperative salvage autotransfusion was able to decrease the morbidity of AKI,while platelet transfusion and vasopressor administration to maintain blood pressure could increase the possibility of AKI.

Objective:To observe the effect of old RBCs transfusion on cognitive function in rats and the improvement effect of mi -nocycline.Methods: Male SD rats at the age of 6 months were randomly divided into 4 groups.The RBCs were obtained from male rats by centrifuging the total blood and stored at 4℃.The rats of fresh RBCs group (group F) were transfused with the RBCs stored for 1 day.The rats of old RBCs group (group O) were transfused with the RBCs stored for 7 days.The rats of treatment group (group T) received 40 mg· kg-1 minocycline with intraperitoneal injection before the transfusion .The rats of the control group ( group C) were transfused with the normal saline .The brain levels of IL-1βand IL-6 were determined with Quantikine ELISA kits in 24 hours after the blood transfusion (n=6).The rats were subjected to Barnes maze tests after 1 week of the blood transfusion (n=10).Results:The brain levels of IL-1βand IL-6 in group O were higher than those in group C and F (P<0.05), which were lower in group T than those in group O(P<0.05).The rats of group O spent longer time finding the target box than those of group C and F in the Barnes maze (P<0.05), and the time was shorter in group T than that in group O (P<0.05).Conclusion: Old RBCs transfusion plays a role in neuro-inflammation and induces cognitive dysfunction in rats , which may be improved by minocycline .

Objective To investigate the mechanism of sleeve gastrectomy combined with modified jejunoileal bypass (SG/MJIB) in improving the blood glucose of Goto-kakizaki (GK) rats.Methods According to the random meter method,the 28 GK rats were divided into 4 groups:sleeve gastrectomy with modified jejunoileal bypass (SG/MJIB),sleeve gastrectomy (SG),modified jejunoileal bypass (MJIB) and sham operation (SHAM).The changes of weight,food intake,fasting blood glucose,oral glucose tolerance test (OGTT),insulin tolerance test (ITT),plasma insulin and gastrointestinal hormonal (ghrelin and GLP-1) were monitored before and 16 weeks after surgery respectively.Results After surgery,the fasting blood glucose level in SG/MJIB group was obviously lower than that in SG,MJIB and SHAM groups (P＜0.05).From the 2nd week after surgery,OGTT of the SG/MJIB group was obviously improved compared to SG,MJIB,and SHAM groups (P＜0.02).In our post-op erative study,the insulin levels in SG/MJIB group were lower than those in SG,and SHAM groups (P＜0.05).Compared to MJIB and SHAM groups,ghrelin levels of SG/MJIB group were significantly decreased (P＜0.001),while GLP-1 levels of SG/MJIB group were higher than those of SG and SHAM groups (P＜0.01).Conclusions SG/ MJIB can improve insulin sensitivity and insulin secretion,and this effect is independent of the body weight and food intake.This study further validates that the gastrointestinal hormones play an important role in the pathogenesis and treatment mechanisms of type 2 diabetes mellitus.

Objective To explore the aging mechanisms of human adult adipose-derived stem cells (hADSCs) in vitro.Methods The hADSCs came from the production of normal patients with liposuction.The hADSCs were cultured in the 37℃ incubator and passed until the cells were senescent.The senescence-associated β-gal staining (SA-β-gal) and histone protein γH2AX staining were carried out in both young and old hADSCs.The quantitative real-time PCR (qRT-PCR) was conducted to check the difference of the transcription function of the young and old hADSCs.Results The cultured hADSCs would be the senescent cells when the PD number was more than 35.The aging cells became big and had large flat nuclei and much more lososomes in the cytoplasm.The SA-β-gal staining and γH2AX staining were mostly positive in the aging hADSCs (PD>35) compared with the self-renewing hADSCs (PD<20).The qRT-PCR results showed that the transcription levels of Nanog and Oct4 gene were very low in aging hADSCs compared with the self-renewing ones.Conclusions The hADSCs will be senescent (SEN) when cultured and passed in vitro for long time and the aging process is similar to that of stem cells in vivo.The aging model of hADSCs can be established by this method and will be very useful in the anti-aging drug, regeneration medicine, tissue engineering and stem cell therapy.