Ten pharmacophore models of beta-tubulin inhibitors were established from the training set of seventeen beta-tubulin inhibitors (two categories) with comformer analysis by using the Catalyst software. The optimal pharmacophore model with two hydrophobic units and two hydrogen bond acceptor units were confirmed (RMS = 0.43, Correl = 0.98, Weight = 2.06, Config = 15.97). This pharmacophore model is able to predict the activity of known beta-tubulin inhibitors and can be further used to identify structurally diverse compounds with higher activity.

Objective:To explore the effect of probiotics on the cognitive function of patients with schizophrenia.Methods:100 schizophrenic patients admitted to Shanghai Jinshan District Mental Health Center from January 2019 to January 2021 were randomly divided into the conventional group (treated with atypical antipsychotics combined with placebo, 50 cases) and the intervention group (treated with atypical antipsychotics combined with probiotics, 50 cases). Before treatment and 3 months after treatment, the feces of the patients were taken for DNA detection to compare the composition of intestinal flora. The cognitive function of the patients was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the mental state of the patients was assessed by the Positive and Negative Symptom Scale(PANSS). The incidence of adverse drug reactions was compared between the two groups.Results:Before treatment, the relative abundance of Fusobacteria, Proteus and Actinobacteria in the two groups had no statistical significant difference (all P>0.05); After 3 months of treatment, the relative abundance of Fusobacteria, Proteus and Actinobacteria in the two groups decreased compared with that before treatment, and the decline was more significant in the intervention group (all P<0.05). Before treatment, there was no significant difference in immediate memory, visual span, speech function, attention function, delayed memory and RBANS between the two groups (all P>0.05); After 3 months of treatment, the scores of immediate memory, visual span, speech function, attention function, delayed memory and RBANS in the two groups were higher than those before treatment, and the increase was more significant in the intervention group (all P<0.05). Before treatment, there was no significant difference in PANSS scores between the two groups ( P>0.05); After 3 months of treatment, PANSS scores in both groups decreased compared with those before treatment, and the decrease degree in the intervention group was higher than that in the conventional group (all P<0.05). During the three months of treatment, there was no significant difference in the incidence of adverse drug reactions between the two groups ( P>0.05). Conclusions:Probiotics are used in adjuvant therapy for patients with schizophrenia, which can regulate the patients′ intestinal flora, improve patients′ cognitive function and mental disorders, and do not increase the incidence of adverse drug reactions. They have significant clinical efficacy and high treatment safety.

Chronic hepatitis C virus (HCV) infection has become a major public health burden worldwide. Twenty-two sophocarpinic acid or matrine derivatives were synthesized and their anti-HCV activities were evaluated in vitro. The structure-activity analysis revealed that (i) sophocarpinic acids with a D-seco 3-ring structure scaffold were more favorable than matrines with a 4-ring scaffold; (ii) the introduction of an electron-withdrawing group on the phenyl ring in 12-N-benzenesulfonyl Δ (βγ) sophocarpinic acids was beneficial for the antiviral activity against HCV. Among them, compounds 9h and 9j exhibited the most potent inhibitory activities on HCV replication with selectivity indies of 70.3 and 30.9, respectively. Therefore, both were selected as antiviral candidates for further investigation.

Chest trauma is one of the most common injuries. Venous thromboembolism (VTE) as a common complication of chest trauma seriously affects the quality of patients′ life and even leads to death. Although there are some consensus and guidelines on the prevention and treatment of VTE at home and abroad, the current literatures lack specificity considering the diagnosis, treatment and prevention of VTE in patients with chest trauma have their own characteristics, especially for those with blunt trauma. Accordingly, China Chest Injury Research Society and editorial board of Chinese Journal of Traumatology organized relevant domestic experts to jointly formulate the Chinese expert consensus on the diagnosis, treatment and prevention of chest trauma venous thromboembolism associated with chest trauma (2022 version). This consensus provides expert recommendations of different levels as academic guidance in terms of the characteristics, clinical manifestations, risk assessment, diagnosis, treatment, and prevention of chest trauma-related VTE, so as to offer a reference for clinical application.

Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.
Antibodies, Monoclonal ; immunology ; therapeutic use ; Antibodies, Monoclonal, Humanized ; immunology ; therapeutic use ; B7-H1 Antigen ; antagonists & inhibitors ; immunology ; Humans ; Neoplasms ; drug therapy ; immunology ; pathology ; Programmed Cell Death 1 Receptor ; antagonists & inhibitors ; immunology ; Signal Transduction ; drug effects ; immunology ; T-Lymphocytes ; immunology