Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Hepatoma is one of the most common malignant tumors of digestive system worldwide， and a main factor leading to cancer-related deaths. Its incidence is increasing year by year， posing a serious threat to human health. Currently， hepatoma is mainly treated by surgical resection， liver transplantation， radiation and drugs， but there are certain adverse reactions and problems of high recurrence rate and low survival rate. Chinese medicine has unique advantages in improving the comprehensive curative effect of hepatoma and reducing adverse reactions. With a variety of active ingredients， Chinese medicine can induce hepatoma cell apoptosis， inhibit the proliferation， migration and reverse multidrug resistance through multiple targets， thus exerting anti-hepatoma effect. It has become an important means for the prevention and treatment of hepatoma as well as a rich resource for anti-hepatoma drug research and development. Wnt/β-catenin signaling pathway， one of the most classical pathways in cancer， is involved in tumor cell proliferation， cell cycle， migration， invasion and tumor angiogenesis. Recently， many studies have reported that the active ingredients of Chinese medicine can play an anti-hepatoma role through this pathway. Therefore， this paper summarized the domestic and foreign literature in recent years， analyzed the relationship between wnt/β-catenin signaling pathway and the specific mechanism of hepatoma occurrence and development， and combed the literature on the effect of flavonoids， terpenoids， alkaloids， polysaccharides and other active ingredients of Chinese medicine on inducing hepatoma cell apoptosis， regulating cell cycle and inhibiting the invasion and metastasis through Wnt/β-catenin signaling pathway. In addition， the paper summarized the research progress of relevant active ingredients of Chinese medicine against hepatoma， to explore their specific mechanism against hepatoma through Wnt/β-catenin signaling pathway， so as to provide theoretical reference for further development of anti-hepatoma drugs.

Next-generation sequencing has revolutionized family-based association tests for rare variants. As the lower power of genome wide association study for detecting casual rare variants, methods aggregating effects of multiple variants have been proposed, such as burden tests and variance component tests. This paper summarizes the methods of rare variants association test that can be applied for family data, introduces their principles, characteristics and applicable conditions and discusses the shortcomings and the improvement of the present methods.
Computer Simulation ; Family Relations ; Genetic Association Studies ; Genetic Variation ; Genome-Wide Association Study/methods* ; Humans

Objective:To investigate efficacy before and after operation of Information-motivation-behavior nursing model in low-temperature plasma tonsillectomy.Methods:A total of 132 cases of tonsillectomy patients admitted to our department of otolaryngology from January 2016 to January 2017 were selected as research objects. All patients were divided into observation group and control group by random number table method, with 66 cases in each group. Cold plasma tonsillectomy was performed in both groups. The control group received routine nursing measures, and the observation group received IMB nursing mode based on the information - motivation - behavioral skills model. The psychological and emotional scores, surgical awareness, behavior and quality of life scores of patients in the two groups were compared.Results:There was no significant difference in Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores of patients in the observation and control groups before nursing, and SAS and SDS scores of patients in the observation group [SAS (40.56±2.12); SDS (40.56±2.12)] and control group [SAS (50.24±2.14); SDS (47.66±2.57)] were significantly decreased after 1 month of nursing ( t value was13.958, P=0.000), and there were statistically significant differences in the scores between two groups ( t value was 26.106, P=0.000). Before nursing, there was no statistically significant difference in surgical awareness between the two groups, and there was a significant difference in surgical awareness between the observation group (96.97%, 64/66) and control group (84.85%, 56/66) 1 month after nursing ( χ2 value was 16.810, P=0.000), and the observation group was higher than the control group. The scores of the observation group on regular work and rest, taking medicine on time, giving up smoking and drinking, healthy diet, and rehabilitation training (96.12±2.33, 95.72±2.16, 96.96±2.56, 95.68±2.14, 96.45±2.69) were higher than those of the control group (88.42±5.12, 89.86±5.33, 90.13±5.22, 87.61±5.36, 88.19±5.43). There was significant difference in those scores ( t value was 8.278-11.360, P=0.000). After 1 month of nursing, SF-36 scores of patients in the observation group (86.47±6.99) were significantly higher than those in the control group (74.28±7.23) and the difference was statistically significant ( t value was 9.848, P=0.000). Conclusions:Information - motivation - behavior nursing model is helpful to improve the psychological state of patients before and after low-temperature plasma tonsillectomy, and improve the patients′ awareness of the operation and quality of life.

To observe three-dimensional changes of dentigerous cyst-associated maxillary canines (DCAMC) in adolescents after marsupialization by using cone beam computed tomography (CBCT).
 Methods: A total of 34 DCAMC patients with dentigerous cyst aged 10-14 were divided into central type and lateral type, while canines on the non-cyst side served as a control. A three-dimensional reference frame was set up to analyze the position, angle changes and influential factors for DCAMC by using CBCT before operation and in 3-6 month after operation.
 Results: 1) Compared with pre-operation, there was significant vertical movement in DCAMC after marsupialization. Tip of tooth moved labially while tooth axis inclined mesiodistally; 2) Horizontal, vertical movement and mesiodistal inclination of DCAMC were significantly greater than those in the health side; 3) Compared with the lateral type DCAMC, the central type DCAMC showed a significant changes in labial inclination; 4) Horizontal movement, mesiodistal and labial inclination of lateral type DCAMC were all evidently greater than those of the central type DCAMC; 5) Vertical movement and inclination of DCAMC after marsupialization were significantly correlated to the time interval (r=0.354, 0.374, both P<0.05), while vertical movement of cuspid in health side was significantly negative correlated with the patients' age and the level of root formation (r=-0.506, -0.721, both P<0.01).
 Conclusion: DCAMC in adolescents can obtain obvious changes in position and angles after marsupialization regardless of the level of root formation, which is beneficial for further orthodontic treatment.
Adolescent ; Child ; Cone-Beam Computed Tomography ; Cuspid ; Dentigerous Cyst ; Humans ; Maxilla

Objective: To explore the relationship between liver controlled attenuation parameters (CAP) and body fat mass and its distribution. Methods: From May to December 2018, 978 adult patients visited at the fatty liver center of the Third People's Hospital of Changzhou were treated. The patient's liver controlled attenuation parameters were measured by transient elastography and the body fat mass and its distribution were measured by bioelectrical impedance technology. Pearson’s correlation coefficient was adopted to describe the correlation between liver CAP value and body mass index (BMI), body fat mass index (BFMI), trunk fat mass index (TFMI), limbs fat mass index (LFMI) and visceral fat area (VFA). Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate BMI, BFMI, TFMI, LFMI and VFA to differentiate the cut-off points and efficacy of CAP for diagnosing grading of fatty liver changes in S0-1 and S2-3. Results: In 653 cases of male, S0 ~ S3 accounted for 4.90%, 3.37%, 22.36% and 69.37%, respectively, and in 325 cases of females, S0 ~ S3 accounted for 7.38%, 6.46%, 13.23% and 72.92%, respectively. Female patients had more visceral, trunk and limbs fat than male (P < 0.01). Body mass, body fat mass, body fat percentage, BMI, BFMI, TFMI, LFMI, and VFA were increased in male and female patients with increasing liver fat grade (P < 0.01). CAP values ​​of male and female patients were positively correlated with BMI, BFMI, TFMI, LFMI and VFA. Percentage of body fat mass increased with increasing liver fat grade (male: F = 13.42, P < 0.001; female: F = 3.22, P = 0.023); while limb fat mass percentage did not increase with liver fat grade (Male: F = 1.13, P = 0.34; female: F = 1.05, P = 0.37). Hepatic steatosis grading (S0 ~ 1 or S2 ~ 3) diagnosed with CAP were distinguished through BMI, BFMI, TFMI, LFMI and VFA. AUC was 0.80 ~ 0.82 in males (P < 0.01), and 0.75 ~ 0.78 in females (P < 0.01). Conclusion The liver CAP value is positively correlated with the body's limbs, trunk and visceral fat, and has a strong correlation with trunk and visceral fat. BMI, BFMI, TFMI, LFMI and VFA up to some extent can identify the CAP diagnosis of grading of fatty liver changes in S0-1 and S2-3.

Objective The aim of our work is to characterize individual normal occlusions to establish appropriate treatment standards for different vertical facial types. Methods A total of 30 patients with near-normal occlusion were grouped into high-angle group (eight cases), medium-angle group (12 cases), and low-angle group (10 cases) according to vertical facial skeletal type. Invivo5 software was used and digital imaging and communications in medicine data were rebuilt to measure the ∠L1/MP, ∠L6/MP, axis corner of L6, cant of occlusion plane, Balkwill angle, and Bonwill triangle of each group. Results Among the groups, the low-angle group had the smallest ∠L6/MP (P<0.05) and largest cant of occlusion. No significant difference was observed among the three groups with regard to the other parameters (P>0.05). Conclusion Patients with low-angle vertical facial skeletal type requires a modified treatment standard. In this group, the treatment standard must ensure that the cant of occlusion plane is more parallel to the Frankfurt horizontal plane compared with those of the other groups, and the axis of L6 is tilted distally relative to the mandibular plane.

In order to cultivate clinical pharmacy undergraduates to have better quality, Chongqing Medical University collaborated with The University of Chicago and University of Cincinnati in the reform of the course of pharmacotherapeutics. We build pharmacotherapeutics series curriculum with the center of disease, construct department of clinical pharmacy for transnational departments, build course leader and teaching team of pharmacotherapeutics series curriculum , compile teaching program and its material of pharmacotherapeutics series curriculum, build pharmacotherapeutics series curriculum and teaching model in line with the current direction of China's education system of clinical pharmacy training, reform teaching methods, and strengthen clinical pharmacy practice and community clinical pharmacy education.

We investigated the molecular characteristics of the full-length genome of 14 dengue serotype 1 virus (DENV-1)strains isolated in Sino-Myanmar border region in Yunnan Province,China during 2013-2015.Isolation of dengue virus was using C6/36 cell culture method.Viral RNA was extracted from virus isolates,and then the full-length genome was amplified by RT-PCR.The homology and phylogenetic analysis was made on the nucleotide and deduced amino acid sequences by bioinformatics software including ClastalX1.83 and MEGA6 etc.Results showed that fourteen strains of DENV-1 isolated from dengue fever cases,of these,9 strains from Ruili City of Dehong Prefecture,3 from Lincang Prefecture,2 from Kunming City.RT-PCR and sequencing indicated that the full-length genes (10 735 nt) of 14 DENV-1 strains were obtained,and their open reading frame (95-10 271) were coded 3 392 amino acid residues.The genotypes of DENV-1 were revealed by homology and phylogenetic analysis based on structural and non-structural proteins.Thirteen were genotype Ⅰ (G-Ⅰ) (7 from indigenous cases in Ruili and Lincang and 6 from imported case from Myanmar to Ruili,Lincang and Kunming),and 1 G-Ⅲ from imported case from India to Kunming.The phylogenic analysis indicated that the 13 isolates from Yunnan divided into 2 phylogenic subgroups,and they had a closer genetic relationship with the strains isolated from Southeast Asia.The gene sequences of the 13 G-Ⅰ strains have been acquired,the rate of their nucleotide homology and amino acid homology were 97.02 ％-100 ％ and 98.78 ％100 ％ respectively.Compared with 6 strains from Southeast Asia,nucleotide homology and amino acid homology were 96.53％-99.53％ and 97.33％-100％ respectively.Compared with prototype strain (US_Hawaii) of DENV-1,nucleotide homology and amino acid homology were 93.76％-94.45 ％ and 95.86 ％-96.91％ respectively.Compared with US_Hawaii strain,there were 44 and 150 different sites in amino acid of structural and non-structural proteins,respectively.The G-1 of DENV-1 have been popular in Sino-Myanmar border region in Yunnan,2013-2015.They have genetic diversity but multiple transmission sources were from Myanmar,and should strengthen control cross-border spread of dengue fever in this region.It is necessary to further study that change of the amino acid sites of Yunnan strains of DENV-1 is related to its antigenicity and pathogenicity.