Objective This study aimed to explore the differences in global and local brain network topological properties between deficient pattern(DP)and excess pattern(EP)of mild vascular cognitive impairment caused by subcortical small vessel disease based on graph theory network.Methods Patients were recruited prospectively and were classified with DP and EP subtype.The global small-world topological attributes and local nodes were calculated for the comparison of DP,EP,and healthy controls(CN)using the GRETNA platform.Results The three groups all had small-world attributes,but only the patients in EP had a significantly lower small world attribute δ in the range of 0.05-0.26 than the control group(P<0.05).The node efficiency and node strength indicators of multiple brain region were able to significantly distinguish the DP group from the EP group.However,there was no positive brain region in the node efficiency of the DP patients(P>0.05),and only a few brain regions showed increased node strength efficiency(P<0.05).Conclusion The results indicate that the syndrome of DP and EP have significantly different neuroimaging phenotypes,providing a basis for further research of biological classification based on Chinese Medicine syndromes.

Objective To investigate the effect of"zero channel"emergency mode on the treatment of patients with severe traumatic brain injury.Methods A total of 147 patients with severe traumatic brain injury admitted to the Second Hospital of Jiaxing from January 2020 to December 2021 were selected as study objects.Sixty-two patients hospitalized in traditional emergency mode from January to December 2020 were included in control group,and 85 patients hospitalized in"zero channel"emergency mode from January to December 2021 were included in observation group.The initiation time of rescue,completion time of CT examination,completion time of blood transfusion,duration of operation,clinical prognosis and complication rate were compared between two groups.Results The initiation time of rescue,completion time of CT examination,completion time of blood transfusion,and duration of operation in observation group were significantly shorter than those in control group(P<0.05).The proportion of good recovery in observation group was significantly higher than that in control group(68.20%vs.38.70%,χ2=12.671,P<0.001).The complication rate of observation group was significantly lower than that of control group(21.18%vs.80.65%,χ2=51.000,P<0.001).Conclusion"Zero channel"emergency mode can effectively shorten the treatment time of patients with severe traumatic brain injury,improve the success rate of rescue,reduce the incidence of complications,worthy of clinical use and promotion.

Objective:To assess the effect of low-dose esketamine on postoperative cognitive function in elderly patients undergoing non-cardiac surgery.Methods:One hundred and twenty-four patients, aged 65-80 yr, regardless of gender, with a body mass index of 18-35 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, were assigned to either esketamine group (group E, n=64) or control group (group C, n=60) using a random number table method. Group E received intravenous esketamine at a dose of 0.5 mg/kg, while group C received an equal volume of normal saline intravenously. Anesthesia was induced with intravenous fentanyl, propofol and rocuronium and maintained using combined intravenous-inhalational anesthesia in both groups. Patient-controlled analgesia was carried out postoperatively. Cognitive function tests including a simple mental state examination, auditory word learning test, tracking connection test A and B, number symbol replacement test, Boston naming test and complex graph test were performed at 1 day before surgery and 30 days after surgery, and postoperative cognitive dysfunction was determined using Z-score method. Delirium was assessed using Confusion Assessment Method from 1 to 7 days after operation. The operative hypotension, postoperative delayed emergence, nausea and vomiting, and hallucinations were recorded. The recovery time of spontaneous breathing, eye opening to verbal command and extubation time were recorded. Results:Compared with group C, the incidence of cognitive dysfunction at 30 days after surgery and intraoperative hypotension was significantly decreased ( P<0.05), and no significant change was found in the recovery time of spontaneous breathing, eye opening to verbal command, extubation time, incidence of postoperative delayed emergence, delirium, nausea and vomiting, and hallucinations in group E ( P>0.05). Conclusions:Low-dose esketamine can improve postoperative cognitive function in elderly patients undergoing non-cardiac surgery.

Objective:To investigate the clinical value of tissue Doppler echocardiography in the evaluation of left ventricular function in patients with pregnancy-induced hypertension.Methods:This is a case-control study, including 100 patients with pregnancy-induced hypertension who received treatment at the Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2019 to May 2022, and an additional 100 healthy pregnant women who underwent physical examination during the same period. All participants underwent two-dimensional echocardiography, pulsed Doppler echocardiography, and tissue Doppler echocardiography. Ultrasound parameters related to left ventricular morphology and function were collected from all participants. The ultrasound parameters related to left ventricular morphology and function between patients with different types of pregnancy-induced hypertension and healthy controls were compared. The correlation between left ventricular function ultrasound parameters and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels was investigated.Results:Patients with pregnancy-induced hypertension, patients with mild preeclampsia, patients with severe preeclampsia, and healthy controls demonstrated differences in interventricular septum thickness during diastole [(10.24 ± 1.18) mm, (11.39 ± 1.24) mm, (11.57 ± 1.29) mm, (8.81 ± 0.95) mm], left ventricular end-diastolic diameter [(47.31 ± 2.81) mm, (49.82 ± 2.89) mm, (52.03 ± 2.94) mm, (46.82 ± 2.76) mm], left ventricular posterior wall thickness [(9.73 ± 1.06) mm, (10.62 ± 1.13) mm, (11.75 ± 1.21) mm, (8.96 ± 0.97) mm], left ventricular inner diameter [(32.82 ± 2.34) mm, (35.48 ± 2.39) mm, (36.04 ± 2.45) mm, (30.41 ± 2.27) mm], and left ventricular mass index [(98.41 ± 7.83) g/m 2, (105.73 ± 8.26) g/m 2, (108.63 ± 8.57) g/m 2, (96.59 ± 7.69) g/m 2]. All of these parameters showed significant differences between patients with different types of pregnancy-induced hypertension and healthy controls ( F = 13.47, 12.61, 16.59, 13.26, 19.73, all P < 0.001). Significant differences were also observed in echocardiographic indices of left ventricular function such as peak velocity ratio of E and A waves, systolic motor amplitude, early peak diastolic velocity to late peak diastolic velocity, and Tei index between patients with different types of pregnancy-induced hypertension and healthy controls ( F = 12.84, 11.27, 14.64, 21.43, all P < 0.001). In patients with pregnancy-induced hypertension, peak velocity ratio of E and A waves, systolic motor amplitude, and early peak diastolic velocity to late peak diastolic velocity were moderately negatively correlated with serum NT-proBNP level ( r = -0.56, -0.43, -0.54, P = 0.029, 0.042, 0.031), while Tei index showed a positive correlation with serum NT-proBNP level ( r = 0.77; P = 0.003). Conclusion:Two-dimensional echocardiography, pulsed Doppler echocardiography combined with tissue Doppler echocardiography can be used to effectively evaluate the changes in left ventricular structure and function in patients with different types of pregnancy-induced hypertension. Monitoring the Tei index using tissue Doppler echocardiography can accurately reflect myocardial injury and functional changes, which has a great clinical application value.

Objective:To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) .Methods:Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified.Results:① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123 + tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group ( P<0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10 5/ml to 3.2×10 6/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8 + PD-1 + LAG-3 + T cells was 10.90%, and the proportion of propidium iodide (PI) - Annexin Ⅴ + T cells and PI + Annexin Ⅴ + T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group ( P<0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group ( P<0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group ( P<0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123 + tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123 + MV4-11 cells, CD123 + Molm13 cells, and CD123 + THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group ( P<0.05) . Conclusion:In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123 + tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.

Objective:To explore the effects of the continuing nursing model based on "Internet +" in premature infants and their families.Methods:Premature infants and their families admitted to the Department of Neonatology, Wenzhou Central Hospital, from July 2021 to October 2022 were selected by convenience sampling. They were randomly divided into control group and observation group, each consisting of 108 pairs. Infants in the control group received routine nursing intervention, while those in the observation group received "Internet +" based continuing nursing based on the care provided to the control group. Physical growth indicators (weight, length, head circumference), Neonatal Behavioral Neurological Assessment (NBNA) scores, family caregiving knowledge and ability scores were measured before intervention (at birth) and after intervention (at 6 months of age) in both groups. The occurrence of delayed physical development and unplanned rehospitalization of premature infants at 6 months of age was also recorded.Results:After intervention, the physical growth indicators, NBNA scores, and family caregiving knowledge and ability scores of both groups improved, with the observation group higher than the control group, and the differences were statistically significant (all P<0.05). At 6 months of age, the observation group had lower rates of delayed physical development and unplanned rehospitalization compared to the control group, with statistically significant differences (all P<0.05) . Conclusions:The continuing nursing model based on "Internet +" can effectively improve the caregiving knowledge and ability of premature infants' families, promote the growth and development of premature infants, and reduce the risk of delayed physical development and rehospitalization.

Objective To establish the ultra-high performance liquid chromatography(UPLC)chromatographic fingerprint of Notopterygii Rhizoma et Radix;To determine the contents of ferulic acid,nodakenin,ammijin,notopterol,isoimperatorin and volatile oil of Notopterygii Rhizoma et Radix from different producing areas;To provide reference for quality evaluation of Notopterygii Rhizoma et Radix.Methods Waters BEH C18 chromatographic column(2.1 mm×150 mm,1.7 μm)was used,with mobile phase acetonitrile-0.02%formic acid aqueous solution gradient elution,flow rate 0.25 mL/min,column temperature 25℃,detection wavelength 330 nm,injection volume 2 μL.UPLC fingerprints of 25 batches of Notopterygii Rhizoma et Radix were established,and the similarity analysis and chemometrics analysis were carried out.The contents of ferulic acid,nodakenin,ammijin,notopterol and isoimperatorin were determined simultaneously,and the contents of volatile oil was determined by steam distillation method.Results Totally 23 common fingerprint peaks were calibrated,11 known components were identified.According to the results of the cluster analysis and principal component analysis,25 batches of Notopterygii Rhizoma et Radix samples were divided into 3 categories,and the 6 potential differential components were screened out by orthogonal partial least squares-discriminant analysis(OPLS-DA).The results showed that the contents of notopterol and volatile oil from Sichuan Province were higher than those from Gansu Province and Qinghai Province.Conclusion The method established in the study is accurate and reliable,which can provide scientific basis and reference for the quality evaluation and control of Notopterygii Rhizoma et Radix.

Objective To investigate the serum levels of soluble programmed death-1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in chronic hepatitis B (CHB) patients with clinical cure, the correlation between programmed death-1 (PD-1) and lymphocytes by flow cytometry, and the recovery of hepatitis B virus (HBV)-specific immunity. Methods A total of 26 CHB patients with clinical cure, 26 treatment-naïve CHB patients, and 26 healthy controls who were diagnosed at the outpatient service of Peking University First Hospital from January to May of 2022 were enrolled, and related clinical data and peripheral blood samples were collected. ELISA was used to measure the serum levels of sPD-1 and sPD-L1, and flow cytometry was used to measure the expression of PD-1 in peripheral blood lymphocytes. CHB patients with clinical cure were compared with the treatment-naïve CHB patients and the healthy controls. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between three groups, and the chi-square test was used for comparison of categorical data between groups. The Pearson correlation analysis or the Spearman correlation analysis was used to investigate the correlation between two continuous variables. Results For the 26 CHB patients with clinical cure, the mean time of antiviral therapy was 8.33 years, with entecavir as the antiviral drug. The CHB patients with clinical cure had significantly higher levels of sPD-1 and sPD-L1 than the healthy controls ( P < 0.05) and significantly lower percentages of PD-1 + cells/lymphocytes and PD-1 + CD8 + T cells/lymphocytes than the treatment-naïve CHB patients ( P < 0.05). In the treatment-naïve CHB patients, the serum levels of sPD-1 and sPD-L1 were moderately negatively correlated with HBsAg level ( r =-0.524 and -0.583, both P < 0.05). The serum levels of sPD-1 and sPD-L1 were moderately positively correlated with PD-1 + CD8 + T cells/lymphocytes ( r =0.535 and 0.419, both P < 0.05). In the CHB patients with clinical cure, the serum levels of sPD-1 and sPD-L1 were not correlated with age, sex, alanine aminotransferase, T cells/lymphocytes, CD8 + T cells/lymphocytes, PD-1 + T cells/lymphocytes or PD-1 + CD8 + T cells/lymphocytes (all P > 0.05). Conclusion The serum levels of sPD-1 and sPD-L1 in treatment-naïve CHB patients are mainly associated with exhausted CD8 + T cells in peripheral blood, while there is no significant correlation between serum sPD-1/sPD-L1 and exhausted CD8 + T cells in peripheral blood in CHB patients with clinical cure.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Objective:To evaluate the long-term safety, tolerability and efficacy of Lacosamide add-on therapy in Chinese children with partial-onset seizures.Methods:SP848 was a global multicenter single-arm study involving 60 Chinese children with partial-onset seizures with the age of 4-17 years who were managed by Lacosamide add-on therapy at seven hospitals across China from April 2018 to May 2019.After treatment with at least two kinds of anti-seizure medications simultaneously or sequentially, partial seizures were still poorly controlled and Lacosamide oral solution (syrup) or tablets were added.The minimum initial oral dose was 2 mg/(kg·d), and the maximum allowable dose was 12 mg/(kg·d)or 600 mg/d during the study period.The dose was adjusted according to the tolerance and seizure control level of partial-onset seizures children.Seizure frequency and the median percentage change in partial-onset seizures per 28 days from baseline to the final visit were recorded, including 50% responder rate and 75% responder rate.Results:A total of 60 Chinese children with the mean age of 9.18 (4.00-15.40) years were included in this interim analysis, involving 39 males and 21 females.The mean course of epilepsy was 5.04 (0.50-15.20) years.A total of 43 patients (71.7%) still have been treated.One patient (1.7%) has completed the 6-12 months of follow-up, and 14 patients (23.3%) have completed the follow-up for less than 6 months.The median change in the frequency of partial seizures every 28 days from baseline to the last visit was -2.91, with its median percentage as -25.46%, and the proportions of ≥50%, while ≥75% responder rate were 40.0% and 28.3%, respectively.A total of 52 patients (86.7%) had 265 treatment emergent adverse events (TEAE), 11 patients (18.3%) had 19 serious TEAE, 37 patients (61.7%) had 127 drug-related TEAE, and 11 patients (18.3%) had 16 TEAE leading to the discontinuation of the trial.The most common TEAE were upper respiratory tract infections (20 cases, 33.3%), followed by drowsiness (16 cases, 26.7%), dizziness (15 cases, 25.0%) and vomiting (13 cases, 21.7%). There were no abnormal changes in the electrocardiographic findings during the treatment.Conclusions:For Chinese patients with partial seizures who are older than the age of 4 years and poorly controlled by other drugs, Lacosamide is effective and well tolerated as an add-on therapy drug.The safety characteristics are consistent with those reported in children and adults.No new safety concerns are identified.