Objective:To analyze the current level and dynamic change of the salary and income satisfaction rate of doctors in Chinese tertiary public hospitals in recent years.Methods:In January 2018, March 2019 and March 2021, the project team of " the third party evaluation of the China Healthcare Improvement Initiative" conducted a questionnaire survey among doctors of 136 tertiary public hospitals in 31 provinces. The first-line clinicians were investigated by stratified sampling method. The salary level and satisfaction of doctors were investigated by questionnaire. Chi square test was used for comparison between groups.Results:The sample size of the three surveys was 20 786, 23 289 and 22 836 respectively. The median value of doctors′ actual income after tax in 2017, 2018 and 2020 was 100 800 yuan, 120 000 yuan, 150 000 yuan respectively, and the median expected annual income after tax was 196 000 yuan, 250 000 yuan and 250 000 yuan. The proportion of doctors satisfied with the current income was 16.5%, 17.8% and 26.9% respectively. The salary and satisfaction rate of doctors had an upward trend, but the overall level was still low.Conclusions:In recent years, the salary of doctors in tertiary public hospitals in China has been improved to a certain extent, but on the whole, it is at a low level, and there is still much room for improvement. In the future, the government needs to improve the hospital salary system and increase the salary of doctors continuously, especially needs to pay attention to the doctors with high education level and intermediate titles.

ObjectiveTo compare the retest reliability and discriminant validity of dynamic postural stability indices for functional ankle instability (FAI) obtained by different algorithms based on acceleration signals at different positions of human body. MethodsFrom April to June, 2021, 21 subjects with unilateral FAI and 21 subjects with normal ankle were recruited. Three inertial sensors were attached to the waist points, knee and ankle positions. The ground reaction force (GRF) and kinematics data of the subjects in multi-direction single leg landing test were collected synchronously by 3D force plate and inertial sensors. The unbounded third order polynomial (UTOP) fitting method was used to calculate the stability time, and the root mean square was used to caculate the stability index. ResultsMost of the indicators calculated based on acceleration signal correlated with that based on GRF with low coefficient (|r| = 0.116 to 0.368, P < 0.05). The stability time and stability index based on the acceleration signals of different positions of human body showed low to high retest reliability (CMC 0.30 to 0.91). For the females, among the stability time based on acceleration signal, eleven indexes achieved average to very high discriminant validity (AUC = 0.702 to 0.942, P < 0.05); eight of the stability indexes reached general level of discriminant validity (AUC = 0.717 to 0.782, P < 0.05). No algorithms achieved good discriminant effect in male subjects. ConclusionBased on the acceleration signal of waist point in single-leg landing stability test, the stability time calculated by UTOP algorithm can evaluate the dynamic postural stability of female FAI patients with high discriminant validity and medium to high retest reliability.

The pathological processes of Alzheimer's disease and type 2 diabetes mellitus have been demonstrated to be linked together. Both PDE9 inhibitors and PPAR agonists such as rosiglitazone exhibited remarkable preclinical and clinical treatment effects for these two diseases. In this study, a series of PDE9 inhibitors combining the pharmacophore of rosiglitazone were discovered. All the compounds possessed remarkable affinities towards PDE9 and four of them have the IC values <5 nmol/L. In addition, these four compounds showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Compound , the most effective one, gave the IC of 1.1 nmol/L towards PDE9, which is significantly better than the reference compounds PF-04447943 and BAY 73-6691. The analysis of putative binding patterns and binding free energy of the designed compounds with PDE9 may explain the structure-activity relationships and provide evidence for further structural modifications.

Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC₅₀ = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A-15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π-π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE-inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.

Objective: To study the effects of Phellodendron amurense on herpes simplex virus 1 (HSV-1) and cytokines, and to explore the mechanism of Phellodendron amurense inhibiting HSV-1 virus through multiple channels. Methods: Viruses were inoculated into medicine treated HeLa cells. The proliferation of virus was observed by fluorescence microscopy. The transcriptional levels of glycoprotein gD and functional protein US1 on the surface of virus envelope were detected by quantitative (q) PCR. After incubating HeLa cells for 24 h, qPCR was used to detect the expression of intrinsic immune factors such as IP-10, IL-12, IFN-gamma and transcription factor NF-kappa B (P65). The expression and nuclear location of NF-kappa B (P65) protein were detected by immunofluorescence. Results: Fluorescence showed that the proliferation of virus decreased significantly at 8 and 40 ng/ml (P<0.01), and the transcription levels of viral protein gD and US1 decreased (P<0.05). After incubation for 24 hours, the transcription levels of IP-10, IL-12 and IFN-gamma in HeLa cells increased significantly (P<0.01). The transcription level of transcription factor NF-kappa B (P65) also increased (P<0.05), and immunofluorescence showed that the nuclear penetration rate of p65 subunit of NF-kappa B (P65) in each group increased (P<0.05). Conclusions Phellodendron amurense extract can inhibit HSV-1 by inhibiting the transcription of viral functional protein and promoting the expression of cellular immune factors.

Optimization efforts were devoted to discover novel PDE10A inhibitors in order to improve solubility and pharmacokinetics properties for a long-term therapy against pulmonary arterial hypertension (PAH) starting from the previously synthesized inhibitor

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

Normal mammalian secondary palate development undergoes a series of processes, including palatal shelf (PS) growth, elevation, adhesion and fusion, and palatal bone formation. It has been estimated that more than 90% of isolated cleft palate is caused by defects associated with the elevation process. However, because of the rapidly completed elevation process, the entire process of elevation will never be easy to clarify. In this article, we present a novel method for three-dimensional (3D) reconstruction of thick tissue blocks from two-dimensional (2D) histological sections. We established multiplanar sections of the palate and tongue in coronal and sagittal directions, and further performed 3D reconstruction to observe the morphological interaction and connection between the two components prior to and during elevation. The method completes an imaging system for simultaneous morphological analysis of thick tissue samples using both synthetic and real data. The new method will provide a comprehensive picture of reorientation morphology and gene expression pattern during the palatal elevation process.

Objective: To carry out the 4^th round of third-party evaluation on the implementation and effect of the 1^st year of the 2^nd Phase National Healthcare Improvement Initiative(abbreviated as Initiative)since 2015. Methods: The 4^th round of the evaluation survey adopted the same methods, organization and execution, and technical roadmap as the former three rounds of evaluations. Results: The 4^th round of evaluation was carried out from 18 March to 9 April, 2019 at 185 public hospitals in 31 provinces(autonomous regions, municipalities directly under the Central Government)and Xinjiang Production and Construction Corps.Facility survey, health professional survey and patient survey were conducted at each of the sample health facilities. A total of 120 782 valid questionnaires were collected from 144 non-psychiatric health facilities, 16 246 valid questionnaires were obtained from 41 psychiatric health facilities, and 252 cases of outstanding departments/hospitals in healthcare improvement were also collected. The average overall scoring of the 12 dimensions to assess Initiative implementation at 144 non-psychiatric health facilities was 84.4%. The overall outpatient satisfaction scoring was 91.1%, 96.7%for the inpatients. The overall inpatient satisfaction(family members inclusive) at 41 psychiatric health facilities was 93%. Areas remaining to be improved include day-surgery, telemedicine and medical social work. Compared with technical services, non-technical care should be further strengthened. The compensation, workload and work environment of the healthcare providers are still to be improved. Conclusions The implementation of the Initiative by health facilities has been greatly improved. The percentage of health facilities and patients who had positive perceptions of improved doctor-patient relationship has been increasing. Patient care experiences at public hospitals have been generally improved, and the implementation of promoting traditional Chinese Medicine practices also made progress. However, work satisfaction of healthcare providers was found to be rather low, compared to the high level of patient satisfaction.