Volume 100 ·  Issue 35 ·  2020

Alzheimer's disease (AD) is the most common type of senile dementia, characterized by progressive neurological degeneration, and is an important cause of disability in the elderly^[1]。 In recent years, scholars have gradually realized that AD is a complex multifactorial disease, in which age, sex, family history and carrying apolipoprotein E (APOE) ε 4 allele are important risk factors for AD. In addition to these uncontrollable risk factors, there are many controllable risk factors, mainly including vascular risk factors, life behaviors, social and psychological factors, etc. In addition, there are a variety of protective factors related to the development of AD, including cultural education in adolescence, work complexity in adulthood, and participation in social, cognitive or intellectual stimulating activities and physical exercise activities in spare time in middle and later years^[2]。

The list of members of the expert group for the formulation of this consensus:

To explore the characteristics of psychiatric symptoms and caregivers’ distress in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.

Seventy-two patients with anti-NMDAR encephalitis were investigated in Peking Union Medical College Hospital from 2011 to 2018. The Chinese version of the Neuropsychiatric Inventory-Questionnaire (NPI-Q) was used to assess the severity of neuropsychiatric symptoms and caregivers’ distress around the treatment.

A highly positive correlation existed between severity scores of neuropsychiatric symptoms and caregiver distress, and pre- and post-treatment correlation coefficients was 0.872 and 0.947, respectively (all P<0.001). The frequency of 12 symptom domains was higher than 45% before treatment, however, it significantly reduced to below 45% after treatment. Irritability/lability, agitation/aggression were the most common neuropsychiatric symptoms. Irritability/lability, agitation/aggression, and nighttime behavioral disturbances occurred concurrently. Patients with severe symptoms tended to be administrated antipsychotics (Z=-2.581, P=0.01). Neuropsychiatric symptoms significantly improved after immunotherapy (Z=-6.611, P<0.001). There was no significant difference in the symptom severity and distress subscale scores between the first episode and relapse around the therapy (P>0.05).

Patients with anti NMDAR encephalitis often present severe neuropsychiatric symptoms, which aggravate the burden on caregivers. Immunotherapy significantly improves neuropsychiatric symptoms, and thus reduces the distress of caregivers.

To evaluate the precision of the robot-assisted sacroiliac screw placement for posterior pelvis injury and the impacting factors.

The clinical data of twenty-four cases of posterior pelvic fractures treated by percutaneous sacroiliac screw placement in Yantai shan Hospital from August 2016 to May 2018 were studied retrospectively. There were 17 males and 7 females with a mean age of 44.1 years (ranged from 17 to 71 years). According to AO classification, 17 cases were type B fractures (9 cases of type B1 and 8 type B2), and 7 cases were type C factures (3 cases of type C1, 2 type C2 and 2 type C3). All cases were treated by robot-assisted percutaneous sacroiliac screw placement (AO cannulated screws with a diameter of 7.3 mm). In the posterior pelvic surgeries for the 24 cases, 26 S₁ sacroiliac screws fixations and 18 S₂ sacroiliac screw fixations were placed in total, with single S₁ segmental fixation in 8 cases, single S₂ segmental fixation in 3 cases, S₁ and S₂ combined fixation in 13 cases, S₁ unidirectional one-sided fixation in 18 cases, S₁ bidirectional two-sided fixation in 3 cases, S₂ unidirectional one-sided fixation in 14 cases, S₂ bidirectional two-sided fixation in 2 cases and S₁ unidirectional double screws fixation in 2 cases. X-ray and CT examinations were taken for all 24 cases after operation. The visual analogue scale (VAS) of pain were performed before and after the operation.

All the sacroiliac screws were successfully implanted at once as planned with the assistance of the robot. The postoperative X-ray films and CT showed that none of the sacroiliac screws broke through the sacral body and the contralateral sacral wing′s frontal cortex nor did they stray into the sacral canal and the intervertebral space. In 3 cases, the sacroiliac screws went closely against and wore out the front edge of iliac cortical density line and sacral alar slope and finally re-entered the sacral body. In 3 cases, sacroiliac screws touched upon the sacral nerve canals but did not break through the nerve canals. The mean VAS of pain was improved from 7.1 points (4-10 points) before the operation to 1.9 points (0-3 points) after.

The robot-assisted sacroiliac screw placement shows high precision, and hence is worthy of clinical promotion; however the primary role of the surgeon could not be replaced.

To evaluate the clinical impact of percutaneous coronary intervention (PCI) on left ventricular myocardial remodeling and main adverse cardiovascular and cerebrovascular events (MACE) in ischemic cardiomyopathy patients with different left ventricular ejection fraction and SYNTAX score≤22.

A total of 191 ischemic cardiomyopathy patients who underwent PCI in Department of Cardiology from May 2017 to October 2018 were enrolled in this study, and they were divided into three groups according to preoperative left ventricular ejection fraction (≥50% group, 36%~49% group and ≤35% group). The main outcomes and left ventricular ejection fraction, left ventricular end-diastolic volume were analyzed at 12 months follow-up. The main outcomes were the recurrence of acute left ventricular failure, recurrent angina, restenosis, revascularization, non-fatal myocardial infarction, cardiovascular death and non-cardiovascular death.

The incidence of MACE was 32.6% (15 cases) in ≥50% group, 32.0% (31 cases) in 36%-49% group, 45.8% (22 cases) in ≤35% group, respectively, which was lower in the first two groups than in ≤35% group, but there was no statistically significant difference among the 3 groups (P=0.231). The incidence of acute left ventricular failure in the three groups was 2.2%, 12.4% and 22.9%, respectively, and there was statistically significant difference among the 3 groups (P= 0.01). Multivariate analysis indicated that preoperative left ventricular ejection fraction ≤35% was an independent predictor of acute left ventricular failure (OR=2.696, 95%CI: 1.099-6.612, P=0.030). Compared with baseline data, left ventricular end-diastolic volume ((62±4) mm vs (56±5) mm, P<0.001), left atrium ((42±6) mm vs (40±6) mm,P<0.001) decreased significantly 1 year after PCI. However, left ventricular ejection fraction ((43±10)% vs (51±13)%,P<0.001) increased significantly. At 1 year, left ventricular remodeling related parameters were detected in 3 groups, and there was statistically significant difference in left ventricular end-diastolic volume ((53.1±0.6) mm vs (55.1±0.5) mm vs (59.1±0.7) mm,P<0.001), left ventricular ejection fraction ((62.1±1.1)% vs (51.4±1.0)% vs (37.0±1.5)%,P<0.001) among the 3 groups.

Coronary vascular reopening with PCI in patients with ischaemic cardiomyopathy and SYNTAX score≤22, can improve prognosis of patients with preoperative left ventricular ejection fraction>35% significantly, but not in those with preoperative left ventricular ejection fraction≤35%. Preoperative left ventricular ejection fraction may be an independent predictor of acute left ventricular failure in patients with ischemic cardiomyopathy and SYNTAX score≤22, postoperative left ventricular remodeling and left ventricular systolic function correlate with preoperative left ventricular ejection fraction.

To investigate the effect and mechanism of Polyphyllin Ⅱ on the proliferation, invasion and chemosensitivity of glioma cells.

CCK-8 cell proliferation assays and Transwell assays were employed to determine the effect of Polyphyllin Ⅱ on the proliferation and invasion of glioma cells (T98G and LN18), respectively. The expression of E-cadherin, Snail and O6-methylguanine DNA methyltranferase (MGMT) were quantified by Western blot analysis.

Polyphyllin Ⅱ could inhibit the proliferation of glioma cells in a time- and does-dependent manner. The half maximal inhibitory concentration (IC₅₀) of T98G at 24 h, 48 h and 72 h were (5.82±0.32), (3.57±0.07) and (1.48±0.35) µmol/L, respectively. The IC₅₀ of LN18 at 24 h, 48 h and 72 h were (6.83±0.11), (4.28±0.29), (2.66±0.22) µmol/L, respectively. After being treated with 2 µmol/L, 4 µmol/L and 6 µmol/L Polyphyllin Ⅱ for 24 h, the percentage of invasive cell area in the chamber area was lower than those in T98G and LN18 control groups (P<0.05). Western blot analysis showed that compared with glioma cells without Polyphyllin Ⅱ treatment, the expression of E-cadherin in T98G and LN18 was higher (F=85.56, P<0.05;F=60.80, P<0.05), but the expression of snail was lower (F=25.34, P<0.05;F=48.28, P<0.05). When temozolomide was used in combination with Polyphyllin Ⅱ at different concentrations, the coefficient of drug interaction (CDI) was less than 1. Western blot showed that MGMT expressions in T98G and LN18 were inhibited compared with glioma cells without Polyphyllin Ⅱ treatment (F=40.38, P<0.05;F=48.44, P<0.05).

Polyphyllin Ⅱ can inhibit the proliferation and invasion of glioma cells, and improve its sensitivity to Temozolomide.

To investigated whether berberine could ameliorate septic cardiomyopathy in a rat model of sepsis and it′s mechanisms.

SD rats were divided into 3 groups: sepsis group (LPS group), rats were intraperitoneal injected of LPS (10 mg/kg); Berberine intervention group (Ber group), Ber (50 mg/kg, one time per day) was gavage fed 3 days before intraperitoneally injection of lipopolysaccharides (LPS); control group (Con group), rats were gavage fed with double distilled water (2 ml/100 g, one time per day) 3 days before intraperitoneal injection of normal saline (1 ml/100 g). LPS group and the Ber group was further divided into 3 subgroups (n=6), and the follow-up experiments were conducted at 6 h, 24 h and 48 h after LPS injection (of which 48 h subgroup rats were gavage fed with Ber/saline at 24 h). Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of change of left ventricular pressure (±dp/dtmax) were monitored, the level of cardiac troponin T (cTnT), tumor necrosis factor (TNF)-α and interleukin (IL)-1β was detected by ELISA method, HE staining of myocardial tissues was done to observe myocardial injury; Western blotting method was used to detect the expression of toll-like receptor 4(TLR4) protein in rat myocardial tissue, the level of myocardial cell nucleus protein p65 was detected to reflects the degree of NF-κB activation. The correlation of factors was analyzed with Pearson correlation analysis.

Pre-treatment with berberine stabilized cardiac hemodynamics and improved the systolic function and diastolic function in the heart of LPS-induced rats, as evidenced by the partial recovery of the reduced±dp/dtmax and LVSP, as well as the decreased LVEDP. Compared with the LPS group, the Ber group showed improved myocardial injury, as demonstrated by decreased cTnT at each time point. HE staining results showed that berberine decreased inflammatory cell infiltration and LPS-induced cell swelling. These effects were observed early at 6 hours, severe at 24 hours, and become more serious at 48 hours after LPS injection. Further, TLR4 and NF-κB p65 subunits, which were the two key factors of the TLR4/NF-κB signaling, were upregulated in the LPS group and attenuated in the Ber group. Consistently, the expression levels of the downstream cytokines TNF-α and IL-1β were lower in the Ber group than those in the LPS group (allP<0.05). Myocardial injury markers were positively correlated with the markers of TLR4/NF-κB signals and the downstream host inflammatory factors (allP<0.05).

Berberine can improve myocardial injury and cardiac function in sepsis rats, the mechanism is considered to be related to that it can inhibit the activation of TLR4/NF-κB signaling pathway induced by LPS and further reducing the production of TNF-α and IL-1β.

To investigate the effect of mild hypothermia therapy on liver after cardiopulmonary resuscitation.

Thirty-three inbred Chinese Wuzhishan (WZS) minipigs, weighted (28±2) kg, were used to establish a ventricular fibrillation model. And 30 animals survived after cardiopulmonary resuscitation reached basic life support. The surviving animals were randomly divided into two groups: mild hypothermia group (group M, n=15) and conventional treatment group (group C, n=15). All the animals were observed for 24 hours. Blood samples were extracted at baseline, 0.5, 1, 2, 4, 6, 12 and 24 h after successful resuscitation. The concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected at the time points. The enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α). The data were compared between the two groups, LSD test was used when the variance was homogeneous, and Tamhane T2 test was used when the variance was uneven.

Eleven pigs (73.3%) in the group M and 8(53.3%) in the group C survived at 24 h after successful resuscitation, with no statistically significant difference between the two groups (χ²=1.229, P=0.225). After successful resuscitation, the AST, ALT increased in both group but less in M group (all P<0.05). After successful resuscitation, the concentrations of TFN-α and IL-6 in the blood increased in both groups, reached the peak at 4h, and then decreased gradually. The concentrations of TFN-α in group M were lower than those in group C at 0.5, 2, 4 and 6 h after successful resuscitation (t=0.01, 0.01, 0.87, 0.86, all P<0.05). The concentrations of IL-6 in the group M were lower than those in group C at 0.5, 1, 2 and 4 h after successful resuscitation (t=0.23, 0.78, 0.11, 0.80, all P<0.05).

After successful resuscitation, the release of inflammatory mediators, such as TNF-α and IL-6, and cell apoptosis may involve in liver ischemia reperfusion injury. After successful resuscitation, the liver undergoes ischemia-reperfusion injury, which may be related to the release of inflammatory mediators such as TNF-α and IL-6. Mild hypothermia therapy can prevent the release of TNF-α, IL-6 to reduce the degree of liver damage after resuscitation.

Alzheimer's disease (AD) has become one of the diseases that seriously endanger the health and quality of life of the elderly worldwide. However, there is no effective drug that can cure AD at present. The main reason for the failure of previous AD drugs in clinical trials may be that the subject's disease course is already at a late stage. If there are biomarkers that can predict AD in the early onset or even asymptomatic stage of AD patients, and then intervene in patients, the appearance of clinical symptoms of patients may be delayed, thus improving the current treatment dilemma of AD. To this end, the research team recruited subjects from a longitudinal study 10 years ago to explore biomarkers for early diagnosis of AD. A total of 739 subjects were enrolled and divided into two stages: discovery and validation of exosomal synaptic proteins and establishment and validation of predictive models. During the discovery and validation stages, exosomal synaptic growth-associated protein 43 (GAP43), Neurogranin, synaptosome-associated protein 25 (SNAP25) and Synaptotagmin 1 in AD and mild cognitive impairment (MCI) subjects were significantly lower than those in the control group (P<0.001), exosomal biomarker levels correlated with levels in CSF (R²=0.54~0.70）。 In order to further verify the predictive ability of these exosomal synaptic proteins on the asymptomatic phase of AD, the team established a predictive model for the population of subjects with normal cognitive function 5 to 7 years ago and now developed AD, and predicted the incidence of this population. Subsequently, the predictive model was further validated in the familial AD cohort. Through ROC curve and ridge regression analysis, exosomal biomarkers had high efficacy to reflect brain pathological changes (AUCs =0.87-0.89), and could detect AD 5-7 years before cognitive impairment.