Objective To explore the distribution and localization of dopamine receptor D3-D5 in the small intestine of different species.Methods The distribution and expression of D3-D5 in the small intestine of mice,rats and rhesus monkeys were detected by immunohistochemistry and Western blotting.The expression of D3-D5 in immunoglobulin A positive plasma cells(IgA+PC)located in the lamina propria(LP)were detected by immunofluorescence double labeling.Results D3 and D5 were widely distributed in the epithelium,LP,submucosal plexus(SMP)and intermuscular plexus(MP)of the small intestine in mice,rats and rhesus monkeys.The distribution of D4 in the small intestinal of mice and rhesus monkeys were consistent with the result of D3 and D5.D4 was distributed only within the epithelium and LP of rat small intestine.D3 and D5 were expressed in the IgA+PC in the LP of mice and rats,whereas D4 was not.Conclusion The distribution and localization pattern of D3 and D5 are similar in the small intestine of mice,rats and rhesus monkeys,whereas those of D4 vary between different species.Dopamine may be involved in regulating the functions of IgA+PC.

ObjectiveTo develop basic training courses for family doctor teams for people with disabilities. MethodsUtilizing the methods and theories of the World Health Organization (WHO) rehabilitation competency framework (RCF), and referring to the WHO universal health coverage global competency framework, the rehabilitation competency characteristics of family doctor teams for people with disabilities in community settings were analyzed, and a basic training course system for these teams based on the RCF was developed. Results and ConclusionBased on RCF, a competency framework for family doctor teams serving people with disabilities has been constructed. The objectives, content and training course system for basic rehabilitation training has been established.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective To investigate the value of multi-phase MRI-based radiomics machine learning models in differentiating small renal cell carcinoma(sRCC)from fat-poor renal angiomyolipoma(fp-AML).Methods 79 cases of sRCCs and 35 cases of fp-AMLs(diameter≤4 cm)which were confirmed by pathology were retrospectively analyzed.The volume of interest(VOI)of the total tumor was manually delineated on the images of T2WI(T2),unenhanced phase(UP),corticomedullary phase(CMP)and nephrographic phase(NP)and then the radiomics of the VOIs were extracted respectively.The training set and the test set were set according to the ratio of 7∶3.The t-test,maximal relevance and minimal redundancy(mRMR)and the least absolute shrinkage and selection operator(LASSO)were used to select the radiomics features.The selected features were used to build classification models with logistic regression(LR)and support vector machine(SVM).The receiver operating characteristic(ROC)curve was used to evaluate the classification performances of the models.Results There were 4,12,3,11 and 15 optimal features obtained from T2、UP、CMP、NP and the combined four phases,respectively.The radiomics features based on NP or the combined four phases with LR model performed best,AUCs were respectively 0.956,0.986 in the training set and both were 0.881 in the test set.Conclusion The multi-phase MRI-based radiomics machine learning model has favorable diagnostic performance in differentiating sRCC from fp-AML.

OBJECTIVES: To study the role and mechanism of autophagy in lipopolysaccharide (LPS)-induced inflammatory response of human alveolar epithelial A549 cells. METHODS: A549 cells were stimulated with LPS to establish a cell model of inflammatory response, and were then grouped (n=3 each) by concentration (0, 1, 5, and 10 μg/mL) and time (0, 4, 8, 12, and 24 hours). The A549 cells were treated with autophagy inhibitor 3-methyladenine (3-MA) to be divided into four groups (n=3 each): control, LPS, 3-MA, and 3-MA+LPS. The A549 cells were treated with autophagy agonist rapamycin (RAPA) to be divided into four groups (n=3 each): control, LPS, RAPA, and RAPA+LPS. The A549 cells were transfected with the Toll-like receptor 4 (TLR4) overexpression plasmid to be divided into four groups (n=3 each): TLR4 overexpression control, TLR4 overexpression, TLR4 overexpression control+LPS, and TLR4 overexpression+LPS. The A549 cells were transfected with TLR4 siRNA to be divided into four groups (n=3 each): TLR4 silencing control,TLR4 silencing, TLR4 silencing control+LPS, and TLR4 silencing+LPS. CCK-8 assay was used to measure cell viability. Western blot was used to measure the protein expression levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4. RESULTS: After stimulation with 1 μg/mL LPS for 12 hours, the levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4 increased and reached the peak (P<0.05). Compared with the LPS group, the 3-MA+LPS group had reduced expression of autophagy-related proteins and increased expression of inflammation-related proteins and TLR4, while the RAPA+LPS group had increased expression of autophagy-related proteins and reduced inflammation-related proteins and TLR4 (P<0.05). The TLR4 overexpression+LPS group had reduced autophagy-related proteins and increased inflammation-related proteins compared with the TLR4 overexpression control+LPS group, and the TLR4 silencing+LPS group had increased autophagy-related proteins and reduced inflammation-related proteins compared with the TLR4 silencing control+LPS group (P<0.05). CONCLUSIONS In the LPS-induced inflammatory response of human alveolar epithelial A549 cells, autophagic flux has a certain protective effect on A549 cells. TLR4-mediated autophagic flux negatively regulates the LPS-induced inflammatory response of A549 cells.
Humans ; A549 Cells ; Autophagy ; Beclin-1/metabolism* ; Caspase 1/metabolism* ; Inflammation ; Lipopolysaccharides/pharmacology* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Toll-Like Receptor 4/metabolism*

Fall efficacy is an important index reflecting the confidence and belief degree of individuals who do not fall in daily activities. Parkinson disease is a common neurodegenerative disease. Due to the deterioration of balance and other functions, the overall fall efficacy level is generally poor, which not only restricts the daily social interaction, but also further degrades the body function, and ultimately leads to the patients′ falling more easily, increased disability and decreased overall quality of life. This paper reviewed the concept, measurement tools, research status, influencing factors and intervention of fall efficacy in patients with Parkinson disease, and pointed out the existing problems and future directions, aiming to provide reference for further research on fall efficacy in patients with Parkinson disease in China.

This study aimed to explore the link between block copolymers' interfacial properties and nanoscale carrier formation and found out the influence of length ratio on these characters to optimize drug delivery system. A library of diblock copolymers of PEG-PCL and triblock copolymers with additional PEI (PEG-PCL-PEI) were synthesized. Subsequently, a systematic isothermal investigation was performed to explore molecular arrangements of copolymers at air/water interface. Then, structural properties and drug encapsulation in self-assembly were investigated with DLS, SLS and TEM. We found the additional hydrogen bond in the PEG-PCL-PEI contributes to film stability upon the hydrophobic interaction compared with PEG-PCL. PEG-PCL-PEI assemble into smaller micelle-like (such as PEG-PCL4006-PEI) or particle-like structure (such as PEG-PCL8636-PEI) determined by their hydrophilic and hydrophobic block ratio. The distinct structural architectures of copolymer are consistent between interface and self-assembly. Despite the disparity of constituent ratio, we discovered the arrangement of both chains guarantees balanced hydrophilic-hydrophobic ratio in self-assembly to form stable construction. Meanwhile, the structural differences were found to have significant influence on model drugs incorporation including docetaxel and siRNA. Taken together, these findings indicate the correlation between molecular arrangement and self-assembly and inspire us to tune block compositions to achieve desired nanostructure and drug loading.

Objective:To observe effect of Zeqi Tang in intervening mice with orthotopic lung cancer model, in order to observe its anti-tumor mechanism. Method:An in situ mouse model of non-small cell lung cancer was established through intrapulmonary injection with 1×10⁵ LLC-luc cells. The model mice were intragastrically administered with Zeqi Tang(0.171 g·mL^-1) or normal saline for 35 days. Appearance (spirit, hair, appetite, sleep), survival period and Zeqi Tang anti-tumor effect were observed, weekly vital imaging was performed to detect the fluorescence signal in the lungs of mice. Flow cytometry was used to detect the NK cell content in the spleen of the model mice. CD107α was used to detect the degranulation of NK cells in the spleen of mice after administration of Zeqi Tang. Kromasil 100 5 C₁₈ column was used and eluted with acetonitrile-0.025%phosphoric acid in a gradient mode, with flow rate at 1.0 mL·min^-1, column temperature at 35℃ and detection wavelength of 265 nm, as to establish the fingerprint of Zeqi Tang. The fingerprints of 10 batches of samples was evaluated by using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System Software (2012 Edition) recommended by the Chinese Pharmacopoeia Commission, in order to complete the quality control of Zeqi Tang. Result:Zeqi Tang could significantly inhibit the lung fluorescence signal of lung cancer in situ model mice and prolong the survival of mice(P<0.05, P<0.01). After the intervention with Zeqi Tang, the NK cells in the tumors increased significantly(P<0.01), and the degranulation of CD107α also increased significantly(P<0.01). Moreover, the HPLC-DAD fingerprint of Zeqi Tang showed a significant increase in the fingerprint similarity of 10 batches of lacquer soup aqueous extract. Moreover, the HPLC-DAD fingerprint of Zeqi Tang showed that the fingerprint similarity of 10 batches of lacquer soup aqueous extract was ≥ 0.9, indicating that small differences between the batches. Conclusion:Zeqi Tang may enhance the tumor growth and prolong the survival period of mice by up-regulating the number of NK cells in mice and enhancing their degranulation function. The evaluation of similarity of HPLC fingerprint of Zeqi Tang reflects the quality of lacquer soup to a certain extent, and can provide reference for further study.

Objective: To explore the recovery time and risk factors of coagulopathy caused by rodenticide poisoning through analyzing and following up the confirmed cases, and to provide more useful guidance information for the clinic practice. Methods: A total of 96 cases with coagulation dysfunction caused by anticoagulant rodenticide poiso-ning in Children′s Hospital, Chongqing Medical University from January 2014 to December 2016, were analyzed retrospectively.The recovery time of coagulation function and the relationship between recovery time and drug involved way, dysfunction organs and poison concentration were studied respectively. Results: (1) A total of 96 patients were hospitalized because of severe coagulopathy caused by the poisoning of second generation anticoagulant rodenticide.Brodifacoum was detected from 33 blood samples and the median concentration was 364 μg/L (55-4 654 μg/L). Bromadiolone was detected from 7 blood samples and the median concentration was 130 μg/L (18-652 μg/L). Brodifacoum and Bromadiolone were both detected from 8 cases and the median concentration was 741 μg/L (63-6 000 μg/L) and 11 μg/L (3-3 694 μg/L), respectively.(2) A total of 57 cases of the patients were successfully followed up.A total of 18 cases were confirmed with oral poisoning, 16 cases with dermal poisoning, while 23 cases denied any involved ways of poisoning, and 7 cases had organs dysfunction.The follow-up time was 12-54 months.All the hospitalized patients were given specific antidote Vitamin K treatment and recovered successfully without any sequelae.(3) The median recovery time of coagulopathy caused by rodenticide poisoning was 2.5 months.(4) The recovery time of coagulation function was positively correlated with the plasma concentration of Brodifacoum(r=0.619, P<0.01). (5) There was no significant correlation between recovery time and organ dysfunction or drug involved ways of poisoning involvement (all P>0.05). Conclusions The recovery time of coagulation dysfunction caused by anticoagulant rodenticide in children is much longer.The higher the concentration of Brodifacoum poison is, the longer the recovery time.Enough supplementation course of Vitamin K should be given according to the follow-up of coagulation function.