Objective To investigate the efficacy of sakubatril valsartan combined with tolvaptan in the treatment of heart failure patients with reduced ejection fraction(HFrEF)and the effects on echocardiography and cardiovascular events.Methods According to the random number table method,400 patients with HFrEF admitted to the First People's Hospital from September 2017 to January 2022 were divided into the control group and the combination group with 200 cases each.Both groups were given conventional treatment,based on which the control group was given sacubitril valsartan and the combination group was given sacubitril valsartan combined with tolvaptan.The efficacy,echocardiographic indexes[left ventricular ejection fraction(LVEF),left ventricular end-diastolic internal diameter(LVEDD),left ventricular end-systolic internal diameter(LVESD)],myocardial injury indexes[serum brain natriuretic peptide(BNP),high-sensitivity troponin T(hs-CTnT),growth transforming factor-15(GDF-15)],urine output,neuroendocrine factors[antidiuretic hormone(ADH),angiotensin(PRA),angiotensin Ⅱ(Ang Ⅱ)],cardiovascular events and adverse effects were compared between the two groups.Results The total effective rate was 94.50%(189/200)higher in the combined group than 86.00%(172/200)in the control group(P＜0.05);LVEF was high-er in the combined group than in the control group after treatment,and LVEDD and LVESD were lower than in the control group(P＜0.05);BNP,hs-CTnT,GDF-15,ADH PRA,and Ang II were lower in the combined group than in the control group,and urine volume was higher than in the control group(P＜0.05);at 6-month follow-up after treatment,there were no statistically significant differences in the rehospitalization rate of heart failure,the incidence of non-fatal infarction,post-discharge cardiovascular mortali-ty and all-cause mortality in the combined group compared with those of the control group(P＞0.05);there were no statistically significant differences in the incidence of adverse events in the combined group compared with that of the control group(P＞0.05).Conclusion Sacubitril valsartan combined with tolvaptan is effective in treating HFrEF,by reducing myocardial inju-ry,promoting urination,and improving patients'cardiac function without increasing the risk of cardiovascular events and adverse reactions.

ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg^-1） and Captopril group （0.002 57 g·kg^-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

The relationship between the duration of type 2 diabetes mellitus (T2DM) and the risk of female reproductive malignancies is complex and multifaceted. Large population cohort studies revealed a negative association between the duration of T2DM and the incidence of breast cancer and endometrial cancer. Furthermore, the risk of breast and endometrial cancer is the highest within a short time after T2DM diagnosis and remains remarkably higher in patients with longer diabetes duration than in the nondiabetic population. This phenomenon suggests causal reverse bias and potential detection bias. Nevertheless, T2DM remains an important risk factor for breast and endometrial cancer. Research on the association between diabetes with cervical and ovarian cancer is limited, and results vary by region. Future epidemiological studies should focus on large prospective studies with long follow-up to further investigate this association. Research into the biological mechanisms linking diabetes and female reproductive cancers is also necessary to develop effective cancer prevention and early intervention strategies.

ObjectiveTo establish the characteristic sugar spectrum of polysaccharides， oligosaccharides and monosaccharides of wild-simulated and transplanted Astragali Radix， and find out the difference of the sugar spectrum between the two， so as to provide a basis for quality evaluation of Astragali Radix. MethodThe relative molecular weight distribution of polysaccharides from 18 batches of wild-simulated Astragali Radix and 12 batches of transplanted Astragali Radix were characterized by high performance liquid chromatography-evaporative light scattering detection（HPLC-ELSD） to establish the characteristic chromatograms of two kinds of polysaccharides. The difference in the peak area ratio of APS-Ⅱ， a polysaccharide component with a relative molecular weight of 10 kDa， in two kinds of Astragali Radix was analyzed， and the critical value of peak area ratio of APS-Ⅱ was determined by receiver operating characteristic（ROC） curve. At the same time， APS-Ⅱ was partially acid-hydrolyzed by trifluoroacetic acid（TFA） to establish characteristic spectra of two kinds of oligosaccharides from Astragali Radix based on HPLC-ELSD， and the characteristics of differential oligosaccharides were found by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Two kinds of APS-Ⅱ were completely acid-hydrolyzed by TFA and derivatized to establish characteristic spectra of two kinds of monosaccharides from Astragali Radix based on HPLC， PCA and OPLS-DA were performed on the peak area ratio of two kinds of monosaccharides to explore the differences in the composition of two kinds of APS-Ⅱ monosaccharides. ResultThe characteristic sugar spectrum of polysaccharides from Astragali Radix showed that the peak area ratio of APS-Ⅱ was the main difference， and the peak area of APS-Ⅱ of wild-simulated and transplanted Astragali Radix were 89.17%-97.17% and 80.14%-91.96%， respectively. The ROC curve determined the critical value of 92.28% for the difference of APS-Ⅱ peak area ratio of the two kinds of Astragali Radix. The multivariate analysis of APS-Ⅱ oligosaccharides revealed that the peak area ratio of oligosaccharides with polymerization degree≥10 was the main difference， which ranged from 11.835%-19.092% for wild-simulated products and 2.778%-7.017% for transplanted products. The results of monosaccharide characteristic sugar spectrum analysis showed that both Astragali Radix species consisted of six monosaccharides， and glucose and arabinose were the differential monosaccharide fractions. The peak area ratios of glucose and arabinose in wild-simulated products were 85%-93.9% and 2.7%-5.8%， respectively， while those of transplanted products were 74.3%-87.3% and 5.3%-10.7%， suggesting that the structures of the two polysaccharide fractions APS-Ⅱ of Astragali Radix may be different. ConclusionThe difference of sugar spectrum between two kinds of Astragali Radix may be related to the content and structure of APS-Ⅱ， and this study may provide a reference for the study of carbohydrates in Astragali Radix and the quality evaluation of medicinal materials.

Poly ADP-ribose polymerase-1 (PARP-1) plays a vital role in organisms, including regulating repair of DNA, maintaining genome stability, regulating cell proliferation, differentiation, and death.At present, PARP inhibitors have been made some breakthrough in the treatment of breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.However, PARP inhibitors have certain limitations in other malignant tumors and patients who are resistant to PARP-1 inhibitors.This article summarizes the research on PARP inhibitors in lung cancer, hepatocellular carcinoma, glioblastoma, leukemia and cervical cancer, and introduces the strategies of combining other anti-tumor drugs such as DNA repair inhibitors, immune checkpoint inhibitors, anti-angiogenic drugs and other chemotherapeutic drugs to solve their drug resistance, which provides some reference for the wide clinical application of PARP inhibitors in the future.

To explore the mechanisms by which AKR1C3 induces tumor resistance, human breast cancer cell strain MCF-7/DOX resistant to doxorubicin, MCF-7/ AKR1C3 cells for overexpression of AKR1C3 and MCF-7/DOX-KD cells for knockdown of AKR1C3 in MCF-7/DOX cells were established. Western blot analysis found that AKR1C3 was expressed at a higher level in MCF-7/DOX than MCF-7 wild type cells. Similarly, CCK-8 and DAPI confirmed that MCF-7/ AKR1C3 cells were more resistant to DOX than AKR1C3 wild types as the IC50 was increased 6 times in MCF-7/AKR1C3 cells more than in AKR1C3 wild type cells. Meanwhile, colony formation ability was also enhanced after AKR1C3 was over-expressed in MCF-7 cells.Cytoplasmic/nuclear separation analysis and IF further found that β-catenin nuclear translocation mediated by AKR1C3 was the main reason contributing to the occurrence of DOX-resistant breast cancer cells. β-catenin inhibitor, XAV939, could reverse the AKR1C3 induced doxorubicin resistance in MCF-7 cells.Results indicated that AKR1C3 could be a potential therapeutic target in breast cancer cells.

Objective:To investigate the clinical features of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis misdiagnosed as mental disorder, improve the early diagnosis rate and reduce misdiagnosis.Methods:The clinical data of patients with anti-NMDA receptor encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University from 2012 to 2018 were collected. Patients misdiagnosed as mental disorders were screened out. Their psychiatric symptom characteristics, disease course characteristics, imaging and laboratory findings, treatment and prognosis were retrospectively analyzed.Results:A total of 121 cases of anti-NMDA receptor encephalitis were collected, and 43 cases of mental disorders were screened out. Sixteen of the 43 patients (37.2%) had prodromal symptoms, and all the patients had psychiatric behavioral abnormalities (100%), including 32 cases (74.4%) of seizures, 13 cases (30.2%) of decreased level of consciousness, 21 cases (48.8%) of involuntary movements, 15 cases (34.9%) of decreased memory, 8 cases (18.6%) of speech dysfunction, and 8 cases (18.6%) of other neurological symptoms (central hyperventilation, autonomic dysfunction). Memory loss was observed in 15 cases (34.9%), speech dysfunction in 8 cases (18.6%), other neurological symptoms (central hypoventilation, autonomic dysfunction) in 8 cases (18.6%), and various symptoms may appear simultaneously or successively in the same patient. Thirty-eight cases had complete resolution of symptoms or only minor physical impairment, and 5 cases had recurrent admissions with mental abnormalities and seizures. The recurrence rate accounted for 11.6% (5/43).Conclusions:The clinical manifestations of anti-NMDA receptor encephalitis are complex and varied. Most of them have mental behavior abnormalities as the first symptom, which is easily misdiagnosed as mental disorder and delayed treatment will lead to prolonged disease course and poor prognosis.

Objective:To explore the effects of habit reversal training on the use of inhaled corticosteroids (ICS) in patients with bronchial asthma.Methods:Select 89 patients with bronchial asthma using ICS admitted to the respiratory department of the Anhui No.2 Provincial People′s Hospital from 2016 January - 2019 January, and they were randomly divided into control group and study group, 45 cases in control group and 44 cases in study group. Patients in the control group received usual care and propaganda measures, the patients in the study group were intervened by the behavioral habit reversal training consisting of consciousness practice, behavior evaluation, antagonistic action training, anxiety management, follow-up and social support.. Asthma control test questionnaire (ACT), self-developed evaluation method of ICS inhalation technique, bronchial asthma quality of life questionnaire (AQLQ), were used to evaluate the difference of inhaled glucocorticoid corticosteroid therapy before and after the intervention.Results:The ICS inhalation technique scores (6.24±0.82) were higher than those of the control group (4.13±0.67), the difference was statistically significant ( t=-13.307, P<0.05). ACT scores of the study group were better than those of the control group ( Z=-2.780, P=0.005), the difference was statistically significant ( P<0.05). After intervention, AQLQ total scores in the study group, and the asthma symptoms, psychological status, and scores of the self-health dimension in AQLQ in the study group were (211.74±29.84), (51.09±6.49), (39.57±5.24), (24.36±3.41), higher than those in the control group(191.18±27.91), and (43.18±5.73), (31.21±4.62), (19.94±2.84), the difference was statistically significant ( t value was -7.988 - -3.358, P<0.05). Conclusion:Habit reversal training can effectively enhance the technical level of bronchial asthma patients operating ICS device, further improve the status of asthma control, improve the quality of life of patients, and improve the quality of nursing services for such patients.

Objective:To evaluate the effect of remote ischemic conditioning (RIC) on left ventricular (LV) myocardial perfusion, myocardial viability, LV remodeling, regional and global LV function serially following acute myocardial infarction (AMI) in Chinese mini-pigs.Methods:AMI was established in 12 Chinese mini-pigs (8 males, 4 females; age: 6-8 months) and they were randomly divided into RIC group ( n=6) and non-RIC group ( n=6). RIC was performed in pigs by blood pressure inflation on the lower limbs for 5 min period and 4 cycles immediately after surgery. A series of myocardial perfusion imaging and gated 18F-fluorodeoxyglucose (FDG) myocardial metabolism PET/CT imaging were performed longitudinally at the 1st, 14th, 28th and 56th days after AMI, and parameters including total perfusion defect (TPD), hibernating myocardium (HM), Scar, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), summed motion score (SMS), summed thickening score (STS) and changes of these parameters were obtained. Independent-samples t test and Mann-Whitney U test were used to analyze data. Results:Nine Chinese mini-pigs survived after surgery and were performed imaging. Compared to non-RIC group ( n=4), HM at the 28th ((6.0±2.4)% vs (17.0±4.6)%; t=-4.158), TPD 14th-1st ((-11.8±5.4)% vs 9.0%(4.5%, 15.0%); z=2.449), TPD 28th-1st ((-15.3±3.9)% vs (12.0±3.0)%; t=-10.071), TPD 56th-1st ((-18.0±6.5)% vs 9.0%(4.5%, 12.0%); z=2.449), HM 28th-1st ((-10.5±6.9)% vs (8.3±2.1)%; t=-4.507), HM 56th-1st (-15.0%(-17.5%, -8.5%) vs 2.0%(0%, 7.0%); z=2.449) and LVEDV 14th-1st (-0.5(-2.5, 0) ml vs (13.0±4.4) ml; z=2.470) were reduced in RIC group ( n=5; all P<0.05). Conclusion:RIC can improve myocardial perfusion, delay LV remodeling in the acute stage and salvage hibernating myocardium in the subacute stage and chronic stage.

Finding stable expression sites on the chromosomes of Chinese hamster ovary (CHO) cells is an effective method to solve the problem of unstable expression of CHO cells in long-term culture. Our group used lentiviral transfection to integrate the tracer gene (Zsgreen1) into the chromosome of CHO cells and found multiple potential stable expression sites. This study verified the ability of one of the sites located in the 148052-148157 bp region on chromosome NW_003614241.1 to stably express exogenous proteins.The expression of Zsgreen1 gene was first observed, and CRISPR/Cas9 technology was then used to integrate the enhanced green fluorescent protein (EGFP) gene into this site. Three strains of EGFP gene integrated cells were obtained. After 60 generations of suspension culture, the fluorescence intensity of the cells had no significant changes, which proved that this site can stably express the EGFP gene. The same method was used to construct recombinant CHO cell lines expressing the human serum albumin (HSA) gene, and was verified by Western blot that this site could express and secrete HSA. It shows that the above-mentioned sites can be integrated and can stably express exogenous proteins.