ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Background: Gut microbiota is closely related to the occurrence and development of diabetes and affects the prognosis of diabetic complications, and the underlying mechanisms are only partially understood. We aimed to explore the possible link between the gut microbiota and vascular inflammation of diabetic mice. Methods: The db/db diabetic and wild-type (WT) mice were used in this study. We profiled gut microbiota and examined the and vascular function in both db/db group and WT group. Gut microbiota was analyzed by 16s rRNA sequencing. Vascular function was examined by ultrasonographic hemodynamics and histological staining. Clostridium butyricum (CB) was orally administered to diabetic mice by intragastric gavage every 2 days for 2 consecutive months. Reactive oxygen species (ROS) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by fluorescence microscopy. The mRNA expression of inflammatory cytokines was tested by quantitative polymerase chain reaction. Results: Compared with WT mice, CB abundance was significantly decreased in the gut of db/db mice, together with compromised vascular function and activated inflammation in the arterial tissue. Meanwhile, ROS in the vascular tissue of db/db mice was also significantly increased. Oral administration of CB restored the protective microbiota, and protected the vascular function in the db/db mice via activating the Nrf2/HO-1 pathway. Conclusion This study identified the potential link between decreased CB abundance in gut microbiota and vascular inflammation in diabetes. Therapeutic delivery of CB by gut transplantation alleviates the vascular lesions of diabetes mellitus by activating the Nrf2/HO-1 pathway.

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8⁺ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

Objective:To study the current status of critical neonatal care centers (CNCC) construction and treatment of critically-ill neonates at city- and county-level in Henan Province.Methods:A questionnaire survey was conducted in January 2022 to city- and county-level CNCC in Henan Province. The basic information of CNCC, ward settings, neonatal management in the Department of Obstetrics and the treatment of critically-ill neonates in 2019-2021 were analyzed.Results:A total of 188 questionnaires were sent and 183 (97.3%) eligible questionnaires were analyzed, including 30 from city centers and 153 from county centers. The bed occupancy rate in county centers was significantly lower than city centers (67.3%±24.1% vs. 86.1%±23.2%), and the doctor/bed ratio, doctor/rescue bed ratio and nurse/rescue bed ratio were significantly higher than city centers ( P<0.05). All city centers had set up independent Department of Neonatology and the number is 92.8% (142/153) in county center. For 80.9% (148/183) centers, neonates were managed in the Department of Obstetrics with consultations and referrals to the Department of Pediatrics and 19.1% (35/183) were managed in the Department of Pediatrics/Neonatology. The average number of deliveries and admissions to the Department of Neonatology in both city and county centers decreased year on year during 2019-2021, but the proportion of premature and low/very low birth weight infants treated in these centers increased year on year. During 2019-2021, the top three diseases treated at the city centers were neonatal respiratory distress syndrome, neonatal asphyxia and acute respiratory distress syndrome, while the top three diseases treated at the county centers were neonatal asphyxia, neonatal respiratory distress syndrome and meconium aspiration syndrome. The incidence of sudden infant death syndrome in city and county centers was (10~30)/100,000. Conclusions:The construction of CNCC in Henan Province is facing challenges such as decreased hospital admissions, increased critically-ill neonates, insufficient cooperation between Obstetrics and Pediatrics and waste of resources. Rationally allocated and optimised use of resources to improve the ability to treat critically-ill neonates is warranted.

Objective:To study the prognostic value of left atrial strain in diastolic function response by treadmill exercise stress echocardiography.Methods:During May 2018 to February 2019, 64 patients underwent treadmill exercise stress echocardiography for diastolic function evaluation in Tangdu Hospital, Air Force Medical University, were recruited.Patients were categorized into diastolic stress test negative group (pre-stress E/e′ <14 & post-stress E/e′<14) (DST- group), and diastolic stress test positive group (pre-stress E/e′ <14 & post-stress E/e′>14) (DST+ group). Patients′ characteristics of the stress test, left ventricular diameter, left atrial volume index, systolic and diastolic function, and left atrial strain parameters were compared between these two groups. ROC analyses were performed based on the echocardiographic parameters with significant group differences ( P<0.01) to determine the predictive values for diastolic stress test response. Results:The pre-stress E/e′ and left atrial strain parameters were significantly differently between DST- and DST+ group. The DST- showed significantly lower E/e′ (8.20±1.27 vs 10.32±1.33, P<0.01), but higher left atrial strains than DST+ group[reservoir function(33.7±5.7)% vs (26.5±5.5)%, P<0.01; conduit function(16.8±4.0)% vs (11.8±3.4)%, P<0.01; pump function(16.9±5.7)% vs (14.7±5.5)%, P<0.05]. The left atrial reservoir function, conduit function and pre-stress E/e′ could predict the diastolic stress test response, the areas under ROC curve were 0.81 ( P<0.01), 0.62 ( P=0.04) and 0.71 ( P<0.01). Conclusions:The left atrial strain parameters under resting condition could predict the diastolic stress test response. It may serve as an alternative method of exercise stress echocardiography for diastolic function evaluation.

The aim of this paper was to observe the combination therapy with total triterpenoids of Chaenomeles speciosa and omeprazole on indomethacin-induced gastric ulcer in rats, and explore its possible mechanism. Rats were randomly divided into normal group, model group, omeprazole monotherapy(3.6 mg·kg~(-1)) group, total triterpenoids of C. speciosa monotherapy(100 mg·kg~(-1)) group, total triterpenoids of C. speciosa and omeprazole combination therapy(100 mg·kg~(-1)+3.6 mg·kg~(-1)) group. Except for the normal group, the other groups were given indomethacin(20 mg·kg~(-1)) by oral once a day for 7 consecutive days. Then the treated groups were given corresponding drugs by gavage, once a day for 14 consecutive days. The next day after the last administration, half of the rats in each group were measured the gastric mucosal blood flow, gastric juice volume and serum TNF-α, IL-1β, IL-6, IL-4 and IL-10. After the remaining rats in each group were underwent pyloric ligation 4 hours after the last administration, the gastric endocrine volume, pH value and total acidity of gastric secretion were measured, then histological analysis was performed, MPO activity, cAMP content and histomorphological analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of gastric tissue TNF-α,IL-1β, IL-6, IL-4, IL-10, VEGFA, A_(2A)R; the protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue were detected by Western blot. The results indicated that total triterpenoids of C. speciosa and omeprazole combination therapy might significantly increase gastric mucosal blood flow, gastric mucus volume, reduce gastric endocrine volume, secretion acidity and mucosal damage, decrease the levels of TNF-α,IL-1β and IL-6, increase the levels of IL-4 and IL-10 in blood and gastric tissue, inhibit the activity of MPO, increase the content of cAMP in gastric tissue, up-regulate the mRNA expressions of VEGFA, A_(2A)R and protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue, elevate p-PKA/PKA, p-CREB/CREB and p-EFGR/EFGR. Moreover, the combination therapy with total triterpenoids of C. speciosa and omeprazole was more obvious than those of two monotherapies. These aforementioned findings suggested that the combination therapy with total triterpenoids of C. speciosa and omeprazole on indomethacin-induced gastric ulcer have significant therapeutic effect on indomethacin induced gastric ulcer in rats, its mechanism might be related to regulating A_(2A)R/AKT/CREB, A_(2A)R/VEGFA, EGF/EGFR and MUC6/TFF2 signaling pathways, inhibiting pro-inflammatory factors, increasing gastric mucosal blood flow, up-regulating mucosal cell proliferation factors and promoting mucosal protective factors.
Animals ; Cytokines ; Gastric Mucosa ; Indomethacin ; Omeprazole ; pharmacology ; Phytochemicals ; pharmacology ; Random Allocation ; Rats ; Rosaceae ; chemistry ; Stomach Ulcer ; chemically induced ; drug therapy ; Triterpenes ; pharmacology ; Tumor Necrosis Factor-alpha

OBJECTIVE: To compare the effects and medication cost of tenofovir disoproxil and entecavir in the treatment of hepatitis B. METHODS: A total of 300 patients with HBV infection selected from our hospital during Sept. 2015-Sept. 2016 were randomly divided into tenofovir disoproxil group and entecavir group, with 150 cases in each group. Tenofovir disoproxil group was given Tenofovir disoproxil fumarate tablet 300 mg orally, qd. Entecavir group was given Entecavir tablet 0. 5 mg orally, qd, for consecutive 48 weeks. HBV-DNA level, negative conversion rate of HBV-DNA, ALT level and ALT normalization rate were compared between 2 groups before treatment, after 24, 48 weeks of treatment. The medication cost-effectiveness ratio and ADR were compared between 2 groups after 48 weeks of treatment. RESULTS: There were no statistical significances in the level of HBV-DNA between 2 groups before treatment, the level of ALT and ALT normalization rate before treatment, after 24, 48 weeks of treatment (P>0. 05). Compared with entecavir group, the level of HBV-DNA in tenofovir disoproxil group after 24, 48 weeks of treatment was decreased significantly (P<0. 05); the negative rate of HBV-DNA in tenofovir group was slightly higher after 24 weeks of treatment, without statistical significance (P>0. 05); the negative rate of HBV-DNA was slightly increased after 48 weeks of treatment (P<0. 05). Negative conversion rate of HBV-DNA and medication cost-effectiveness ratio of ALT normalization in tenofovir disoproxil group were better than entecavir group (P<0. 05). The incidence of ADR in tenofovir dipivoxil group was lower than entecavir group (P<0. 05). CONCLUSIONS: Tenofovir dipivoxil can effectively treat HBV, and its effects and medication cost are both better than entecavir.

Objective To compare the effect of breast conserving surgery and modified radical mastectomy on the clinical efficacy of patients with early breast cancer.Methods CNKI,Chinese Journal Full-text Database (CJFD),China Biology Medicine Disc (CBMdisc),China Dissertation Database (Chinese Dissertation Database,CDDB) google academic and other databases were comprehensive searched.And then the search time was limited to between January 1,2015 and September 1,2017.Key words can be locked for breast conserving surgery,improved surgery for breast surgery,case-control studies,etc.,and then meet the conditions of the literature into the study,for a retrospective analysis.The authors reviewed the literature independently,extracted data and evaluated the risk of bias,and used Review Manager 5.3 software for systematic analysis.Results A total of 1 093 patients with early breast cancer were enrolled in the study.The Meta-analysis showed:there was a significant difference in operation time between the two groups(MD =-30.71,95％ CI:-31.96--29.46,P ＜ 0.01);there was a significant difference in intraoperative blood loss between the two groups(MD =-53.30,95％ CI:-55.38--51.22,P ＜ 0.01);there was a significant difference in postoperative hospital stay (MD =-5.66,95％CI:-7.17--5.17,P ＜0.01) and the incidence of complications (OR =0.30,95％ CI:0.19-0.47,P ＜ 0.01)compared with modified radical mastectomy in early breast cancer patients.There was no significant difference between the two groups in the postoperative recurrence and metastasis (OR =0.78,95％ CI:0.54-1.13,P =0.19).Conclusions In the choice of surgical methods,breast-conserving therapy is better than modified radical surgery,and postoperative recurrence and metastasis rate has no significant difference.

Objective To investigate the value of S-Detect classification in differential diagnosis of breast mass . Methods The data of forty-seven patients with breast mass lesions ( n=61) from our hospital during January to December in 2016 were retrospectively analyzed . Both the man-made BI-RADS classification ( identified by three different specialist physicians with 2 ,5 and 7 years of experience , respectively) and computer S-Detect classification were performed . The sensitivity ,specificity ,accuracy , positive predictive value and negative predictive value of the man-made BI-RADS classification and S-Detect classification of the benign or malignant diagnosis of breast lumps were calculated . The ROC curve was further plotted ,and the area under the curve ( AUC) of each group was compared ,respectively . Results Sixty-one breast mass lesions were confirmed 36 benign lesions and 25 malignant lesions by pathological biopsy . The sensitivity ,specificity and accuracy of man-made BI-RADS classification were as follows:2-year experience physicians 69 .4％ ,72 .0％ and 70 .5％ ;5-year experience physicians:64 .0％ ,92 .0％ and 75 .4％ ;7-year experience physicians:69 .4％ , 92 .0％ and 78 .7％ . The diagnostic sensitivity , specificity , and accuracy of S-Detect classification were 80 .6％ ,96 .0％ and 86 .9％ . The specificity ,accuracy and positive predictive value of S-Detect classification were significantly higher than those of 2-year experience physicians by BI-RADS classification ( P <0 .05) . The area under the ROC curve of each group was 0 .729 ,0 .786 and 0 .801 for 2 , 5 and 7-year experience physicians , respectively , and 0 .917 for S-Detect classification . Conclusions Compared with the man-made BI-RADS classification ,S-Detect classification has advantages in diagnosis of the benign or malignant of breast mass and is helpful to improve the accuracy of diagnosis , especially for junior physicians .