Objective:To discuss the inhibitory effects of combined application of chlorogenic acid(CA),procyanidin(PC),and paeoniflorin(PF),the active components of Paeoniae Radix Rubra,on Enterococcus faecalis(E.faecalis)and its biofilm,and to clarify the mechanism.Methods:The minimal inhibitory concentration(MIC)and minimal bactericidal concentration(MBC)of CA,PC,and PF against E.faecalis were detected by microdilution method;the fractional inhibitory concentration index(FICI)and fractional bactericidal concentration index(FBCI)of the three active components of Paeoniae Radix Rubra in combination were detected by checkerboard dilution method.The experiment was divided into control group,high concentration of single-drug groups(PF-10 group,PC-6 group,and CA-10 group),and drug combination groups(CA-2+PC-1 group,CA-2+PC-2 group,PF-4+PC-2 group,PF-6+PC-2 group,PF-4+CA-4 group,and PF-6+CA-4 group).Crystal violet staining was used to detect the biofilm formation of E.faecalis in various groups after treated with three active components in combination;scanning electron microscope(SEM)was used to observe the morphology of E.faecalis biofilm in various groups after treated with three active components in combination;spot assay was used to detect the inhibitory effects of three active components in combination on E.faecalis planktonic bacteria and biofilm in various groups;SEM was used to observe the damage to E.faecalis cell membrane in various groups after treated with three active components in combination;kit was used to detect the adenosine triphosphate(ATP)levels in E.faecalis planktonic bacteria and biofilm in various groups after treated with three active components in combination.Results:Among the three active components of Paeoniae Radix Rubra,the MIC of PC was 4 g·L?1 and the MBC was 6 g·L?1;the MIC of CA was 8 g·L?1 and the MBC was 10 g·L?1;the MIC and MBC of PF were both>10 g·L?1,and the concentration of PF was selected as 10 g·L?1.The combination of PC and CA showed synergistic effects,the combination of PC and PF showed additive effects,and the combination of CA and PF showed additive effects.The crystal violet staining results showed that compared with control group,the biofilm formations of E.faecalis in PF-10 group,PC-6 group,CA-10 group,and drug combination groups were significantly decreased(P<0.05);compared with PF-10 group,the biofilm formations of E.faecalis in PC-6 group,CA-10 group,CA-2+PC-1 group,CA-2+PC-2 group,PF-4+PC-2 group,PF-6+PC-2 group,and PF-6+CA-4 group were significantly decreased(P<0.05 or P<0.01).The SEM results showed that in control group,the E.faecalis biofilm was thick,with tightly connected bacteria,regular morphology,and intact cell membranes;in PF-10 group,PC-6 group,and CA-10 group,the thickness of E.faecalis biofilm was significantly reduced,and the arrangement of bacteria became relatively loose;in all drug combination groups,the E.faecalis biofilm was significantly reduced or even completely disappeared,and under high magnification,the biofilm structure was completely absent,with bacterial fragments adhering and aggregating,losing their original bacterial morphology.The spot assay results showed that compared with control group,the colonies of E.faecalis planktonic bacteria in PF-10 group,PC-6 group,and CA-10 group were significantly reduced after treated for 5,10,and 30 min,indicating gradually enhanced bactericidal effects;among drug combination groups,the combination of CA and PC significantly reduced the colonies of E.faecalis planktonic bacteria within 5 min,showing strong bactericidal effects.Compared with CA group and PC group,the colonies of E.faecalis planktonic bacteria in all drug combination groups showed no significant reduction after treated for 5,10,and 30 min;compared with control group,the colonies of E.faecalis biofilm in PF-10 group,PC-6 group,and CA-10 group were gradually decreased after the treated for 30 and 60 min,suggesting that the high concentration of single-drug groups exhibited gradually enhanced bactericidal effects on E.faecalis in biofilm.Among them,the biofilm-killing effect of PC-6 group was the most significant,with no colony formation observed after treated for 30 min;in drug combination groups,only a few colonies of E.faecalis biofilm were observed in CA-2+PC-2 group after treated for 30 min,indicating effective killing of bacteria in biofilm;compared with PC-6 group and CA-10 group,all drug combination groups achieved the bactericidal effects of high concentration of single-drug groups at low concentrations.The SEM results showed that in control group,E.faecalis exhibited an oval shape with intact cell membranes;in PF group,bacterial morphology was altered,and cell membrane integrity was damaged;in CA group,most bacterial cell membranes remained relatively intact,but the bacterial surface showed shrinkage and depression,with a few bacteria exhibiting disrupted cell membrane integrity;in PC group,the integrity of bacterial cell membranes was most severely damaged,leading to leakage of cellular contents and aggregation of cell fragments into flocculent structures;in all drug combination groups,E.faecalis exhibited ruptured cell membranes,leakage of contents,and aggregation of bacterial debris,especially in the combination of CA and PC,where the most severe disruption of bacterial cell membrane integrity and complete leakage of contents were observed;in the combination of PF and CA,bacterial surface pits and shrinkage were observed,with occasional cell membrane rupture.The kit results showed that compared with control group,the ATP levels in E.faecalis planktonic bacteria and biofilm in various groups were significantly decreased(P<0.01);compared with PF-10 group,the ATP levels in E.faecalis planktonic bacteria in CA-10 group,CA-2+PC-2 group,PF-4+CA-4 group,and PF-6+CA-4 group were significantly decreased(P<0.05 or P<0.01),and the ATP levels in E.faecalis biofilm in CA-10 group and CA-2+PC-2 group were significantly decreased(P<0.05 or P<0.01).Conclusion:The combined application of PF,PC,and CA,the active components of Paeoniae Radix Rubra,exhibits significant inhibitory effects on E.faecalis and its biofilm formation.The pairwise combinations of three active components show synergistic or additive effects,with the combination of CA and PC demonstrating the most significant synergistic effect.The underlying mechanism may be related to the disruption of E.faecalis cell membrane integrity and inhibition of bacterial ATP levels.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To investigate the clinical, neuropsychological, and neuroimage characteristics in patients with corticobasal syndrome (CBS), and to elucidate the exact diagnosis of CBS patients.Methods:Twelve CBS cases admitted to the Department of Neurology, Huashan Hosiptal,Fudan University from April 2019 to July 2021 were retrospectively enrolled in this study. Those data, including clinical features (demographic data and clinical characteristics of cortical dysfunction and movement disorder), neuropsychological assessment [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales score], brain magnetic resonance imaging (MRI) and multi-mode positron emission tomography (PET)/CT, were collected and carefully reviewed. Exact diagnosis of these patients was given according to the disease diagnosis criteria.Results:Cortical dysfunction and asymmetrical movement disorders were found in all cases, with poor response to levodopa. Patients suffered from cognitive impairment (MMSE score 16.16±9.82, MoCA score 13.44±7.35). The cranial MRI demonstrated significant asymmetric atrophy of frontal and parietal lobes, especially in the pre- and post-central gyrus. Fluorodeoxyglucose PET of 12 patients showed asymmetric frontal lobe and basal ganglia (especially caudate and putamen) hypometabolism (obviously on the contralateral side of the affected limb). Tau PET was implemented in 11 patients and displayed that abnormal tau protein deposition was positive in the cortex and/or subcortex in all patients. Of the 4 cases, who completed amyloid PET, amyloid protein deposition was positive in the cortex of 2 patients. As a result, 6 patients were diagnosed as progressive supranuclear palsy, 1 patient was diagnosed as corticobasal degeneration, and 5 patients were diagnosed as Alzheimer′s disease.Conclusions:The etiology of CBS is heterogeneous. The combination of clinical manifestation, cranial MRI and multi-mode PET/CT helps the differential diagnosis of CBS.

Objective:To explore the effects of 5E rehabilitation nursing model on self-management behavior and fatigue symptoms of patients with chronic obstructive pulmonary disease (COPD) .Methods:Totally 110 COPD patients admitted in Yantai Yuhuangding Hospital from October 2018 to September 2019 were selected by convenient sampling, and divided into the control group ( n=53) and the experimental group ( n=57) according to the random number table. Excluding missing patients and patients with incomplete data, finally 48 patients were included in the control group and 51 patients were included in the experimental group. Patients in the control group received routine care and health guidance, while patients in the experimental group received care based on the 5E rehabilitation nursing model. The Self-Management Scale for COPD Patients and the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) were used to evaluate the effects of interventions in the two groups. Results:There was no statistically significant difference in the scores of the Self-Management Scale between the two groups before intervention ( P>0.05) ; the scores of all dimensions the Self-Management Scale of the experimental group were higher than those of the control group 12 weeks after discharge, and the differences were statistically significant ( P<0.05) . There was no statistically significant difference in fatigue scores between the two groups before intervention and 12 weeks after discharge ( P>0.05) . Conclusions:The 5E rehabilitation nursing model can improve the self-management behavior of COPD patients, but it cannot ameliorate the fatigue symptoms of patients. Large-sample, multi-center, and long-term research will be further needed in the future to explore the effects of the 5E rehabilitation nursing model on patients' fatigue symptoms.

Objective: To quantitatively measure biological parameters of nanophthalmos and analyze the correlation between axial length (AL) and the other biological parameters. Methods: The clinical data of 71 eyes of 43 patients identified with nanophthalmos (AL≤20 mm) from September 2012 to August 2018 in Zhongshan Ophthalmic Center were retrospectively analyzed.All enrolled patients underwent ophthalmological examinations including best-corrected visual acuity, refraction, slit-lamp biomicroscopy, fundus examination, Goldmann applanation tonometry, A-scan ultrasound examinations, ultrasound biomicroscopy, spectral domain optical coherence tomography (SD-OCT) and nonmydriatic fundus photography.Pearson correlation analysis was used to analyze the relationship between AL and all biological parameters.This study followed the Declaration of Helsinki and was approved by the Ethics Committee of Zhongshan Ophthalmic Center (NO.2017KYPJ092). All patients signed informed consent. Results: Of the 43 patients, the average age was (46.00±12.75) years, the mean intraocular pressure was (24.97±14.87)mmHg (1 mmHg=0.133 kPa). The mean best corrected visual acuity was 1.14±0.79, the mean refraction was (11.61±4.09)D.The mean AL, central corneal thickness (CCT), central anterior chamber depth(ACD), anterior chamber width (ACW), len thickness(LT) and vitreous cavity length(VCL) was (17.13±1.57)mm, (550±60)μm, (1.64±0.37)mm, (11.17±0.61)mm, (5.01±0.51)mm and (10.10±1.80)mm, respectively.The average retinal nerve fiber layer thickness (mRNFLT), macular foveal retinal thickness (FRT) and subfoveal choroidal thickness (SFCT) was (98.51±40.93), (294.46±116.83) and (488.72±133.06)μm, respectively.The ratio of ACD to AL, LT to AL, and VCL to AL was 9.6%, 29.4% and 59.3%, respectively.The ACW and VCL were positively correlated with AL(r=0.432, 0.978; both at P<0.001); whereas, LT and FRT were negatively correlated with AL(r=-0.272, P=0.027; r=-0.679, P<0.001). There was no correlation between CCT, central ACD, mRNFLT, SFCT and AL (r=0.153, -0.053, -0.322, 0.063; all at P>0.05). Conclusions Nanophthalmos has the characteristics of narrow anterior and posterior segment structure.The ratio of LT to AL is increased and the ratio of VCL to AL is decreased.The AL is positively correlated with ACW and VCL, negatively correlated with LT and FRT.

Objective To investigated the relationship between plasma sclerostin(SOST)and knee osteoar-thritis(KOA). Methods A total of 95 patients with KOA and 95 healthy people were involved.Plasma sclerostin, CTX-II, AGG1 and AGG2 levels were measured by ELISA. The 95 patients were divided based on Kellgren-Law-rence classification. The correlation between plasma SOST level and KL classification, CTX-II, AGG1 and AGG2 were analyzed.Results Plasma SOST level in KOA was significantly lower than that in control group(P<0.001). SOST level was negatively correlated with KL grade (r =-0.828,P < 0.001),also with CTX-II (r =-0.917,P <0.001),AGG1 (r =-0.658,P < 0.001) and AGG2 (r =-0.583,P < 0.001). Conclusions SOST level in KOA patients is related to the degree of cartilage degeneration. Thus, it helps to monitor the progress and evaluate the severity of the KOA.

Clinically, kidney?yang deficiency is one of the main TCM syndromes in patients with major depressive disorder. Warming yang and reinforcing kidney as a therapeutic measure for the treatment of depressive disorder has a?chieved good clinical curative effect. However, there are some problems on the study of kidney?yang deficiency depression. One of the reasons is that the establishment methods of depression animal model with kidney?yang deficiency are not uni?fied. In order to provide reference and further improve the replication method of depression animal models with kidney?yang deficiency, we systematically collected and analyzed the experiment results published in the past 15 years about the depres?sion animal model with kidney?yang deficiency induced by glucocorticoid hormone drugs and find out their similarities and differences.

Objective To investigate the effect of acarbose on waist circumference (WC) in patients with IGR. Methods A total of 46 subjects with IGT (2 hPG>7.8 mmol/L) were selected in this study. All the subjects were given diet and exercise treatment for half a month and then treated with acarbose for 3 months in combination with life style modification. Self-paired method was adopted to compare islet βcell function and WC before and after the treatment. Results After acarbose treatment for 3 months ,islet βcell function were markedly improved. Insulin secretion of Fins and 2 hIns decreased ,early insulin secretion index (ΔI30/ΔG30 ) significantly increased ,and BMI and WC were reduced significantly (P<0.05) . Multiple regression analysis showed that there was correlation between WC and TG ,insulin resistance index (HOMA-IR) and islet β-cell function index (HOMA-β) (P< 0.05). Conclusion Acarbose in combination with life style modification can improve islet β-cell function in patients with IGR and reduce WC and abdominal fat accumulation as well.

[Abatract] In order to improve the result of clinical practice for undergraduate students of clinical medicine, combined with the professional characteristics of hematology and teaching syllabus, Hematology Department in the First Affiliated Hospital of Dalian Medical University developed practi-cal teaching content and tried using a variety of teaching methods and teaching means such as multi-media aided teaching, case teaching and simulation teaching method and so on. Besides, multiple station examination was established; teaching feedback and supervision were strengthened. The prac-tice proved that the reform measures were conducive to the cultivation of medical students' practical skills and clinical thinking, which helped to speed up the transformation from the students to the role of doctors.