Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; alpha-Synuclein/metabolism* ; Male ; Prefrontal Cortex/drug effects* ; Rats, Sprague-Dawley ; Depression/metabolism* ; MAP Kinase Signaling System/drug effects* ; Rats ; Parkinson Disease/metabolism* ; Receptor, trkB/metabolism* ; Phosphorylation ; Disease Models, Animal ; Signal Transduction

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of generic drugs and original drugs of voriconazole. METHODS The information of patients who used voriconazole generic drugs selected in National Centralized Drug Procurement （generic drug group） or non-selected original drugs （original drug group） in the treatment of fungal infection was collected from the our hospital. The propensity score matching was carried out to eliminate bias. The comprehensive efficacy was evaluated according to clinical efficacy， image findings and microbiological test， and stratified analysis of different populations was conducted based on fungal species， underlying diseases， etc.， the efficacy of different stratifications was evaluated. Evaluation of safety was performed by using the incidence of adverse reactions. The total cost， defined daily doses （DDDs） and defined daily dose cost （DDDc） were used to evaluate the cost-effectiveness. RESULTS A total of 436 patients were included， and there were 190 patients in each group after matching. In terms of efficacy， the effective rates of voriconazole generic drugs and original drugs were 62.63% and 59.47% （P＝0.528）； in terms of safety， the incidence of adverse reactions caused by generic drugs and original drugs of voriconazole was 13.68% and 7.89%， respectively（P＝0.069）. In terms of cost-effectiveness， the average total cost of generic drugs was 4 636.26 yuan， and that of original drugs was 8 613.20 yuan （P＜0.001）. After the implementation of National Centralized Drug Procurement， replacement rate of generic drugs increased to 87.30%， and DDDc decreased by 59.08%. CONCLUSIONS The efficacy and safety of voriconazole generic drugs are similar to those of original drugs in the treatment of fungal infection， and it is more cost-effective in terms of treatment cost.

Objective:To investigate the clinical characteristics of patients with combined oxidative phosphorylation deficiency type 4 (COXPD4) related to TUFM gene variation, in order to improve clinicians′ understanding of the disease. Methods:A case of COXPD4 with cystic leukodystrophy admitted to the Children′s Hospital of Zhengzhou University in June 2021 was taken as the study subject, and her clinical characteristics and genetic testing results were retrospectively analyzed. The "combined oxidative phosphorylation deficiency type 4" " TUFM gene" "cystic leukodystrophy" "combined oxidative phosphorylation deficiency 4" "COXPD 4" " TUFM" and "cystic leukodystrophy" were used as keywords, and the documents on COXPD4 related to TUFM gene mutations were reviewed from Wanfang Data Knowledge Service Platform, CNKI, PubMed Document Database, and National Center for Biotechnology Information (NCBI) until August 2021. The COXPD4 patients that have been reported internationally were analyzed for clinical features and variant types. Results:The patient was a 2-month-old girl with clinical manifestations of delayed development and progressive aggravation, elevated lactic acid in serum and cerebrospinal fluid, and diffuse white matter dysplasia with multiple cystic lesions in cerebral magnetic resonance imaging (MRI). Whole exome sequencing showed TUFM gene complex heterozygous variants c.684_684+4delGGTGA and c.1105C>T, which had not been reported in the past. A total of 5 cases of COXPD4 were reported in 4 English literatures. Together with 1 case in this study, there were 4 cases with detailed clinical history data, including 1 male and 3 females. The clinical manifestations were severe early-onset lactic acidosis and developmental lag, and 3 cases were accompanied by progressive infantile encephalopathy. Among them, 3 cases underwent head MRI examination, all of which showed diffuse white matter signal with multiple cystic lesions, 2 cases with basal ganglia involvement and multiple cerebellar gyri deformity. Genetic test indicated different types of TUFM gene variation. Conclusions:COXPD4 is a rare hereditary mitochondrial disease. For cases with COXPD4 clinical and imaging features, TUFM gene mutations can be screened first.

Morels (Morchella spp.) are valuable medicinal and edible mushrooms. In this study, chemical profiles of aromas and lipophilic extracts of black morel (Morchella importuna) grown in China were analyzed by gas chromatography/mass spectroscopy, along with the evaluation of antioxidant and antimicrobial activities for the lipophilic extracts. Sixty-five compounds in total were identified from the aromas, and 1-octen-3-ol was the main component for aromas of fresh (34.40%) and freeze-dried (68.61%) black morels, while the most abundant compound for the aroma of the oven-dried sample was 2(5H)-furanone (13.95%). From the lipophilic extracts, 29 compounds were identified with linoleic acid as the main compound for fresh (77.37%) and freeze-dried (56.46%) black morels and steroids (92.41%) as the main constituent for an oven-dried sample. All three lipophilic extracts showed moderate antioxidant activities against 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) with the IC50 values ranging 7.56 ∼ 17.52 mg/mL and 5.75 ∼ 9.73 mg/mL, respectively, and no obvious antimicrobial activity was observed for lipophilic extracts. The drying methods affect the chemical profile of black morel, and freeze-drying was favorable for retaining nutrients and morel smell. This is the first report on the aroma and lipophilic extracts of M. importuna grown in China.

Objective:To observe the effect of early mechanical ventilation on the expression of inflammatory factors and prognosis of patients with severe traumatic brain injury (sTBI).Methods:From January 2017 to December 2020, 138 patients with sTBI admitted to the department of the emergency of Xinhua Hospital Chongming Branch were enrolled. Although some patients were admitted to hospital without acute respiratory failure, their Glasgow coma score (GCS) were less than 8, they bad risk of hypoxia, so early mechanical ventilation was required. According to the patient's condition and the willingness of family members, patients were divided into mechanical ventilation group (tracheal intubation mechanical ventilation) and conventional oxygen inhalation group (nasal catheter or mask oxygen inhalation) in the end. The arterial partial pressure of oxygen (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2), oxygenation index (PaO 2/FiO 2), tumor necrosis factor-α (TNF-α), and interleukin (IL-6, IL-10) levels at admission, preoperation and 72 hours postoperation, as well as GCS before operation and 1 week after operation, the duration and number of patients successfully evacuated from the ventilator within 1 week after surgery were observed and analyzed. Results:A total of 138 sTBI patients were enrolled in the study, including 72 cases in the mechanical ventilation group and 66 cases in the routine oxygen inhalation group. In the two groups, PaO 2, PaO 2/FiO 2 and IL-10 were higher, and PaCO 2, TNF-αand IL-6 were lower at 72 hours post operation than that before operation. Moreover, the changes in the mechanical ventilation group were more significant than those in the conventional oxygen inhalation group [PaO 2 (1 mmHg = 0.133 kPa): 94.6±7.7 vs. 92.5±6.8, PaO 2/FiO 2 (mmHg): 351±94 vs. 319±89, IL-10 (ng/L): 8.2±2.7 vs. 7.4±1.8, PaCO 2 (mmHg): 35.6±1.8 vs. 37.5±2.7, TNF-α(ng/L): 71.5±6.3 vs. 96.8±15.5, IL-6 (ng/L): 10.8±3.9 vs. 14.4±6.5, all P < 0.05]. There were 17 patients with severe respiratory insufficiency or failure in the conventional oxygen inhalation group before operation. Compared with the conventional oxygen inhalation group, the GCS score (11.7±3.1 vs. 9.1±4.6) and the proportion of successful weaning [62.5% (45/72) vs. 44.0% (29/66)] were significantly higher, and the duration of successful weaning (hours: 63.5±28.6 vs. 88.1±33.9) was significantly shorter in the mechanical ventilation group 1 week after operation. Conclusion:Early mechanical ventilation in sTBI patients can significantly improve oxygen supply, inhibit the release of pro-inflammatory factors, reduce secondary brain damage, and effectively improve the prognosis.

Objective To evaluate the application of the dual-energy CT (DECT) in detection of monosodium urate (MSU) crystals in gout patients.Methods The imaging and clinical data of 101 patients with suspected gout were retrospectively analyzed,including 64 cases of clinically diagnosed gout (gout group) and 37 non-gout cases (non-gout group).The DECT examination was performed for 85 joints in gout group and 42 joints in non-joint group.The value of DECT in detection of MSU crystals was evaluated with receiver operating characteristic (ROC) curve.Results There were significant differences in gender (x2=5.32,P=0.03) and blood uric acid levels (t=1.95,P=0.04) between gout and non-gout groups.The detection rate of MSU in gout group was significantly higher than that of non-gout group (x2=30.52,P＜0.001).The area under the ROC curve (AUC) of DECT in detection of was 0.74±0.05 (Mean±SE),95％CI:0.64-0.85.The sensitivity,specificity,positive predictive value and negative predictive value of the DECT in detection of gouty stone was 0.844,0.703,83.1％ and 72.2％,respectively.Conclusion The dual-energy CT has high sensitivity,specificity and reliability for the detection and diagnosis of monosodium urate crystals in joints of gout patients.

Objective To detect the expression of caveolin-1 and PY14caveolin-1 in different esophageal tissues,and study the relationships between the expressions of caveolin-1 and PY14caveolin-1 with the occurrence and development of esophageal squamous cell carcinoma.Methods The fresh surgical specimens in 60 patients with esophageal squamous cell carcinoma were collected and Western blotting were used to analyze and detect the expressions of caveolin-1 and PY14caveolin-1 in esophageal squamous cell carcinoma,adjacent esophageal tissues and normal esophageal tissues.The expression of cav-1 and PY14caveolin-1 with esophageal squamous cell carcinoma were analyzed.Results The expressions of caveolin-1 and PY14caveolin-1 in esophageal squamous cell carcinoma were much higher than that in adjacent tissues and normal esophageal tissues,and the difference between them was statistically significant(P＜0.05).Conclusion The expression of caveolin-1 and PY14caveolin-1 in esophageal squamous cell carcinoma, adjacent esophageal tissues and normal esophageal tissues decreases successively,it suggests the caveolin-1 and PY14caveolin-1 may be the key of the occurrence and development of esophageal cancer cells and they could be involved in the migration and invasion of esophageal cancer.

BACKGROUND:The treatment of autologous pericardium transplantation has been widely applied in clinics, mainly involving cardiovascular repair and reconstruction, the treatment of ocular surface disease. The study addressing protection effects of autologous pericardium transplantation on the heart with ischemia injury is rarely reported. The investigations on the safety and protection effects of autologous pericardial transplantation on the heart with ischemia injury are of important significance.
OBJECTIVE:To explore effect of autologous pericardial transplantation on cardiac electrical activity and the protective effects on myocardial ischemia.
METHODS:Rongchang pork pigs and Sprague-Dawley rats were randomly divided into three groups:autologous pericardium transplantation, myocardial ischemia, and myocardial ischemia+autologous pericardium transplantation. The model of myocardial ischemia was established by ligation of the left anterior descending coronary artery in the groups of myocardial ischemia and myocardial ischemia+autologous pericardium transplantation. The model of transplantation was established by autologous pericardium transplant with flap in the groups of autologous pericardium transplantation and myocardial ischemia+autologous pericardium transplantation.
RESULTS AND CONCLUSION:Porcine electrocardiogram monitoring results showed that, superventricular premature beat was frequently observed in each group of pigs;the ventricular premature beat was occasional observed in autologous pericardium transplantation group, ventricular tachycardia and ventricular fibril ation did not appear. Compared with myocardial ischemia group, the ventricular premature beat decreased and the heart function was improved in myocardial ischemia+autologous pericardium transplantation group (P<0.05). Rat electrocardiogram monitoring results showed that, the ventricular fibril ation did not appear in autologous pericardium transplantation group, the lethal ventricular fibril ation did not appear in myocardial ischemia and myocardial ischemia+autologous pericardium transplantation groups. Compared with myocardial ischemia group, the heart function was improved, the apoptosis index decreased, the expressions of Bcl-2 protein increased, the expressions of Caspase-3 protein decreased in myocardial ischemia+autologous pericardium transplantation group (P<0.05). The autologous pericardium transplantation with flap cannot induce malignant ventricular arrhythmia and is relatively safe;the ventricular premature beat is reduced, the cardiac function is improved, which is possibly related to the inhibition of apoptosis in myocardial ischemic area.

BACKGROUND: Electrical stimulation at different intensity, frequency and time on the human body may produce a variety of pathophysiological reactions. OBJECTIVE: To observe the effects of surface electric-impulse stimulation on heart rhythm and heart rate in mice. METHODS: Thirty Kunming mice were randomly divided into three groups, each group contained 10 mice. Electrical stimulation at different voltage, time and frequency was respectively applied to the three groups. The stimulus power was supplied by BL-420F Data Acquisition & Analysis System. The II lead electrocardiogram was recorded. The systemic reactions and local body changes of mice were observed.

ObjectiveTo investigate the effects of propofol and etomidate on apoptosis in hippocampal neurons in rats.MethodsOne hundred and forty male 4 weeks old SD rats were randomly divided into 7 groups (n =20 each):control group (group C) ; groups P1,2,3 received intraperitoneal (IP) propofol 50,100 and 200mg/kg and groups E1,2,3 received IP etomidate 10,30 and 60 mg/kg respectively.Arterial blood samples were obtained at 2 h after the animals were fully awake for blood gas analysis.The animals were then sacrificed and their brains removed for microscopic examination of the ultrastructure of neurons in hippocampal CA1 area and detection of Survivin and Caspase-3 mRNA and protein expression in hippocampus by RT-PCR and Western blot analysis.ResultsThere was no significant difference in PaO2,PaCO2,SaO2,HCO3-,BE and pH value among the 7 groups.The neurons in CA1 area were basically normal in groups C,P1 and E1 while condensation of the chromatin of the nucleus and apoptotic bodies were observed in groups P3 and E3.Caspase-3 mRNA and protein expression was significantly up-regulated while Survivin mRNA and protein down-regulated in groups P3 and E3.Conclusion High dose of propofol and etomidate may induce apoptosis in hippocampal neurons in rats by up-regulation of Caspase-3 expression and down-regulation of Survivin expression.