ObjectiveTo explore the possible mechanism of Gengxin Decoction （更欣汤） in the treatment of perimenopausal insomnia from the perspective of the expression of oestrogen receptor and orexin A （OXA） in hypothalamic tuberomammillary nucleus （TMN）. MethodsFemale ICR mice with regular estrous cycle were selected to establish perimenopausal insomnia mice models by injecting 4-vinylcyclohexene diepoxide （VCD） combined with para-chlorophenylalanine （PCPA） suspension intraperitoneally. After successful modeling， 75 mice models were randomly divided into model group， zopiclone group and low-， middle-， and high-dose Gengxin Decoction， with 15 mice in each group， and 15 normal mice were set as blank group. On the next day after successful modelling， mice in the low-， middle-， and high-dose Gengxin Decoction were given Gengxin Decoction granules 1.15， 2.3 and 4.6 g·kg^-1·d^-1 by gavage at 9：00 AM every day， mice in the zopiclone group were given zopiclone suspension 1.13 mg·kg^-1·d^-1 by gavage at the same time point， and mice in the blank and model groups were given distilled water 1 ml·kg^-1·d^-1 by gavage at the same time point， for 14 days in all groups. During the experimental period， general conditions of the mice in each group， such as daytime activities， mental state， diet and coat colour， were observed； twenty-four hours after the final intervention， the sleep latency and sleep duration of mice were detected by sodium pentobarbital synergy test， and the levels of serum estradiol （E₂）、progesterone （P）、follicle stimulating hormone （FSH） and OXA protein in TMN of hypothalamus were detected by ELISA， and the protein optical density values of estrogen receptor α （ERα）， OXA and ERβ in TMN was detected by immunofluorescence staining. ResultsThe circadian rhythm of mice was regular in the blank group； the circadian rhythm of mice was disordered in the model group， and they remained active during the day and night； the mental state of mice in each group of Gengxin Decoction was improved compared with that before， which showed that the daytime activity was less than before， and the coat color was slightly yellow but shiny， and the mental state of mice was significantly improved in the middle-dose Gengxin Decoction； the zopiclone group was less active during the day than before， had rough， less shiny hair， and was more alert. Compared with the blank group， the sleep latency of mice in the model group prolonged， the sleep duration shortened， serum E₂ and P decreased， serum FSH and the expression of OXA protein in TMN region increased， the optical density of ERα and ERβ in TMN region decreased， and the optical density of OXA increased （P＜0.05 or P＜0.01）. Compared with the model group， the sleep latency of the mice in the low-， middle-， and high-dose Gengxin Decoction groups and the zopiclone group shortened， the sleep duration prolonged （P＜0.01）； the serum E₂ and P in the middle-， and high-dose Gengxin Decoction groups increased， FSH and the expression of OXA protein in TMN area decreased （P＜0.05）； the optical density values of ERα in TMN area increased in the medium-dose group， and the optical density value of OXA decreased in low- and middle-dose Gengxin Decoction groups， and the optical density values of ERβ in TMN area increased in low-， middle-， and high-dose Gengxin Decoction groups and the zopiclone group （P＜0.05 ）. Compared with the zopiclone group， mice in the low-dose Gengxin Decoction group had longer sleep latency and shorter sleep duration， and mice in the middle- and high-dose Gengxin Decoction groups had higher serum E₂ level and ERβ optical density value in the TMN area， and lower serum FSH and OXA level in the TMN area （P＜0.05）. Compared with the low-dose Gengxin Decoction group， the sleep latency of mice in the middle- and high-dose Gengxin Decoction groups shortened， and the serum FSH level reduced （P＜0.01）. ConclusionGengxin Decoction may inhibit arousal and improve perimenopausal insomnia by modulating the distribution of estrogen receptors and OXA in the TMN region， and inhibiting the overactivation of the orexin system in the TMN region.

Whether direct manipulation of Parkinson's disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6-10 months), and thus provides a practical transgenic monkey model for future PD studies.
Animals ; Brain ; CRISPR-Cas Systems/genetics* ; Dependovirus/genetics* ; Haplorhini ; Phenotype ; Protein Kinases/genetics*

ObjectiveTo explore the relationship between schizotypal personality traits and creativity in college students and the mediating role of cognitive flexibility. MethodsSchizotypal Personality Questionnaire （SPQ）， Cognitive Flexibility Inventory （CFI） and Williams Creative Aptitude Test （WCAT） were used to assess 471 college students. Thereafter， Spearman correlation analysis was used to explore the relationship among the variables and the Bootstrap methodology was used to estimate the mediating role of cognitive flexibility. ResultsThe total SPQ， positive and disorganized schizotypal traits scores， and CFI score were all positively correlated with WCAT score （r=0.241~0.313， P<0.01）. The total SPQ， positive and disorganized schizotypal traits scores were also positively correlated with CFI score （r=0.111~0.128， P<0.05）. Cognitive flexibility mediated the relationship between positive schizotypal traits and creativity ［indirect effect=0.052 （95% CI： 0.016~0.112， P<0.01）， accounting for 11.93% of the total effect］. Cognitive flexibility mediated the relationship between disorganized schizotypal traits and creativity ［indirect effect=0.075 （95% CI： 0.020~0.161， P<0.01）， accounting for 11.50% of the total effect］. ConclusionSchizotypal personality has a direct impact on the creativity of medical students and also cause an indirect impact on their creativity through the mediating role of cognitive flexibility.

Whether direct manipulation of Parkinson’s disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6–10 months), and thus provides a practical transgenic monkey model for future PD studies.

The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.
Betacoronavirus ; isolation & purification ; Child ; Coronavirus Infections ; diagnosis ; pathology ; therapy ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis ; diagnostic imaging ; etiology ; pathology ; therapy

Betacoronavirus ; isolation & purification ; Child ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; drug therapy ; therapy ; Humans ; Pneumonia, Viral ; diagnosis ; therapy

Objective:To evaluate the accuracy of lung recruitment maneuver (LRM) combined with brachial artery peak velocity variation (ΔVp) in predicting fluid responsiveness.Methods:Sixty-four patients of both sexes, aged 18-64 yr, with body mass index 19-26 kg/m 2, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with New York Heart Association class Ⅰor Ⅱ, scheduled for elective open gastrointestinal surgery under general anesthesia, were enrolled in this study.LRM (positive airway pressure was maintained at 30 cmH 2O for 10 s) and volume loading test were performed in sequence after anesthesia induction.ΔVp was measured by ultrasonography at the beginning of LRM.Mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP) and stroke volume (SV) were recorded before LRM (T 1), during LRM (T 2), before volume expansion (T 3) and after volume expansion (T 4). The changing rate of each index before and after LRM (ΔMAP LRM, ΔHR LRM, ΔCVP LRM, ΔSV LRM) and before and after volume expansion (ΔMAP VE, ΔHR VE, ΔCVP VE, ΔSV VE) were calculated.ΔSV VE≥15% was considered to be a positive response after volume expansion, and patients were divided into response group (≥ 15%, R group) and non-response group (< 15%, NR group). Results:There were 34 cases in R group and 30 cases in NR group.Compared with NR group, MAP at T 2 and SV at T 1, 2 were significantly decreased, ΔMAP LRM, ΔMAP VE, ΔSV LRM and ΔSV VE were increased, and ΔVp was increased in group R ( P<0.05). There was a positive correlation between ΔVp and ΔSV VE ( r=0.829, P<0.05), a negative correlation between ΔSV LRM and ΔSV VE ( r=-0.876, P<0.05), and a negative correlation between ΔVp and ΔSV LRM ( r=-0.819, P<0.05). The area under the receiver operating characteristic curve of LRM combined with ΔVp was 0.808, and the cut-off value was 32.3%, the sensitivity 75.3%, and the specificity 88.2%. Conclusion:LRM combined with ΔVp (≥32.3%) can accurately predict the intraoperative fluid responsiveness in patients.

Objective: To investigate the prognostic factors of hyperamylasemia following pancreaticoduodenectomy (PD) . Methods: Clinical data of 359 patients were collected prospectively who underwent PD by the same group at Changhai Hospital of Navy Medical University from January 2017 to June 2018.There were 212 males and 147 females.The median age was 63 years old (range: 23 to 82 years old) .According to whether the patient′s serum amylase was greater than 120 U/L at 0 or 1 day after surgery,the patients were divided into hyperamylasemia group and non-hyperamylasemia group. Univariate analysis and multivariate analysis were used to find out the prognostic factors of hyperamylasemia after PD. Results: Of the 359 patients, 238 cases (66.3%) developed hyperamylasemia.The incidence rate of clinically related pancreatic fistula (15.1% vs.2.5%, P<0.01) , grade B/C post pancreatectomy hemorrhage (8.8% vs. 2.5%, P<0.01) , and surgical site infection (9.2% vs. 3.3%, P=0.04) was significantly higher in the hyperamylasemia group.The severity of complications (CD grade≥Ⅲ: 11.3% vs.4.1%, P=0.023) and postoperative hospital stay (11 days vs. 9 days, P=0.001) were higher in the hyperamylasemia group.In the multivariate analysis, the main pancreatic duct diameter (MPD) ≤3 mm (OR=4.469, 95% CI: 2.563-7.793, P<0.01) , pathological type of disease (pancreatic cancer or pancreatitis) (OR=0.230, 95% CI: 0.122-0.436, P<0.01) and soft texture of pancreas (OR=3.297, 95%CI: 1.930-5.635, P<0.01) were independent prognostic factors for hyperamylasemia. Conclusions Post-PD hyperamylasemia increased the incidence and severity of postoperative complications after PD.MPD≤3 mm, soft texture of pancreas and pathological type of disease were independent prognostic factors of hyperamylasemia.

Objective: To explore the association between the efficacy of peg-IFN and the complexity of TP and RT regions of hepatitis B virus (HBV) in chronic hepatitis B. Methods: Patients with HBeAg positive, HBV DNA positive chronic hepatitis B were given peg-interferon 180 μg once a week for subcutaneous injection, and baseline information was collected from baseline and after 12 weeks’ treatment. The baseline HBV DNA TP and RT fragments were amplified, database, high-throughput sequencing, and the average genetic distance calculation. Results: Data of 108 patients were analyzed by logistic regression. RT area fragment Markov distance and TP area fragment Shannon quotient for HBV DNA response were calculated. ALT level is good for HBeAg response. HBsAg level is bad for HBsAg response. Conclusions The complexity of the baseline TP and RT regions may be associated with the efficacy of peg-interferon therapy for CHB.

Objective: To learn the impact of abolishing medicine markups on the revenue structure of public hospitals in Qingdao city. Methods: The business performance of 12 public hospitals directly under the Qingdao Health and Family Planning Commission was analyzed to compare their revenue structure the year before (July 2015 to June 2016) and the year since the reform (July 2016 to June 2017). Results: The reform has witnessed increased government subsidies, and decreased revenue from drugs and healthcare materials. For example, the proportion of drug expenditure decreased from 44.21% to 32.71%, while the proportion of medical service income and that of examination and laboratory examination increased to some extent. Conclusions Given the initial success of the reform, challenges remain in further curbing revenues from examinations and checkups, and growing revenue from TCM drugs as well.