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 observe the therapeutic effect of Professor Deng's Jinfu An Decoction(JAD)on intermediate and advanced non-small cell lung cancer(NSCLC).Methods Ninety patients with intermediate and advanced NSCLC were equally randomized into 3 groups.GroupⅠreceived routine chemical therapy(CT), groupⅡreceived oral use of JAD,which is mainly composed of raw Arisaema cum Bile,raw Rhizoma Pinelliae, Radix Pseudostellariae,Culmus Phragmitis,Poria,Semen Persicae,Bulbus Fritillariae Thunbergii,Gekko Chinensis,Pseudobulbus Cremastrae seu Pleiones,Radix Salviae Mihiorrhizae,and groupⅢreceived JAD + CT. Three weeks constituted one phase,two phases constituted one treatment courses,and the treatment lasted 2 courses.The changes of clinical symptom and signs scoring,tumor mass,immune function,hemorrheological indexes,and quality of life(QOL)as well as body weight and toxic and side reactions were observed in the three groups.Results The symptom scores decreased in the 3 groups obviously(P0.05).Between the 3 groups,the improvement of QOL in groupsⅡandⅢdiffered from that in groupⅠ(P

OBJECTIVE: To evaluate the cytotoxicity of a new type of titanium alloy Ti-25Nb-10Ta-1Zr-0.2Fe by studying the induced proliferation of L929 cells in contrast with other titania widely used in clinical practice. METHODS: The cell line was treated with extracting liquid containing different concentrations of titanium alloys. The number and morphology of cells was observed under an inverted phase contrast microscope. MTT was used to measure the relative growth rate (RGR) and judge the cytotoxicity grade. Flow cytometry was used to observe cell cycle progression. RESULTS: The RGR of TNTZ group cells at the 3 time points was (93.7±0.8), (100.6±0.4), and (106.4±0.3); the cytotoxicity grade was 1, 0 and 0 after treating for 1, 3 and 5 days; with influence on neither the cell morphology nor the cell cycle. The flow cytometry showed that the sequence of S phase cells was Ti>TNTZ>TC4>blank control >TC4ELI, with no significant difference (P>0.05). None of the 4 materials inhibited the cell proliferation. CONCLUSION The cell morphology and proliferation are not affected by TNTZ. The new titaniu alloys shows good cyto-compatibility. The cytotoxicity is grade 0, meeting the clinical application standard.
Alloys ; toxicity ; Animals ; Cell Line ; Dental Alloys ; toxicity ; Fibroblasts ; cytology ; Mice ; Niobium ; Tantalum ; Titanium ; toxicity ; Toxicity Tests ; Zirconium

OBJECTIVETo identify potential mutation of the colony stimulating factor 1 receptor gene (CSF1R) in a large Chinese family affected with hereditary diffuse leukoencephalopathy with spheroids (HDLS) and analyze the genotype-phenotype correlation.

METHODSThe proband was evaluated physically and radiologically to ascertain the HDLS phenotype. Genomic DNA was extracted from peripheral blood samples from family members. The coding region of the CSF1R gene was amplified with PCR and subjected to direct DNA sequencing.

RESULTSThere were 9 affected members (5 alive) in this five-generation family (1 member had died during the follow-up). A missense mutation c.2563C>A (p.P855T) of the CSF1R gene has been identified in the proband. The same mutation was identified in 3 affected and 1 unaffected members of the family.

CONCLUSIONThe family was consistent with autosomal dominant inheritance. CSF1R gene mutation is also a disease-causing mutation in Chinese patients.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Female ; Genes, Dominant ; Humans ; Leukoencephalopathies ; genetics ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Receptor, Macrophage Colony-Stimulating Factor ; genetics

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.

Objective:To explore the morphological characteristics of the pectoralis major muscle and the anatomical relationship of adjacent structures .Methods:A total of 156 patients undergoing thyroid surgery at the First Hospital of Anhui University of Science & Technology and the First Affiliated Hospital of University of Science and Technology of China from Dec 2020 to Sep 2022 were includeed. Those adopting routine endoscopic thyroidectomy by gasless unilateral axillary approach were assigned to group A,and searching for the sternocleidomastoid muscle through the pectoralis major muscle gap on this basis to group B.Results:Among the 78 patients in group B, a total of 71 (91%) cases were found to have a typical sternocleidomastoid muscle gap, and in 7 (9%) cases were not found. The morphology phenotypes of the gap between the clavicular part and thoracic ribs part of the pectoralis major muscle was found in 3 types: obvious separation type (typeⅠ), inconspicuous separation-partially overlapped type (typeⅡa), and inconspicuous separation-completely anastomosed type (type Ⅱb). The mean duration of surgery in group B was less (105±15) min than that in group A (156±27) min ( t=14.523, P<0.01); postoperative one day drainage in group B was less (49±6) ml than that in group A (51±6) ml ( t=2.273, P=0.024). There was no statistically significant difference in intraoperative bleeding, postoperative hospital stay and complication rate between the two groups ( t=0.557, P=0.578; t=0.134, P=0.894; χ2=1.844, P=0.174). Conclusion:The search for the sternocleidomastoid muscle through the pectoralis major muscle gap in the endoscopic thyroidectomy by gasless unilateral axillary approach can shorten the duration of surgery and improve the efficiency of surgery.

Objective:To investigate the application of post-mortem tissue sampling under ultrasonography guidance in the autopsy of COVID-19 cases.Methods:Ultrasound-guided post-mortem tissue sampling of heart, lungs, liver, kidneys, and spleen were performed in 24 confirmed COVID-19 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from Feb 20 to Mar 28, 2020. Seventeen males and seven females aged 39-91(66.6±10.6) years old were enrolled. The total time required for each post-mortem sampling was recorded, and the size of the samples collected from each organ was measured. The success rate of ultrasound-guided post-mortem tissue sampling for each organ was calculated.Results:Ultrasound images could clearly show the needle path and enabled accurate placement of the needle within the target organs, including heart, lung, liver, kidney, and spleen. The total time required for sampling was about 32-54 (39.8±5.7)min. The lengths of heart, lung, liver, kidney, and spleen tissues collected by ultrasound-guided sampling were 10(8, 14)mm, 13(12, 15)mm, 14(13, 15)mm, 13(11, 15)mm, 14(13, 15)mm, respectively. The success rates of heart, lung, liver, kidney, and spleen tissue sampling under ultrasound guidance were 87.5% (21/24), 91.7%(44/48), 100%(24/24), 89.6%(43/48) and 83.3%(20/24), respectively.Conclusions:Post-mortem sampling under ultrasonography guidance may be a rapid and reliable method for collecting of heart, lung, liver, kidney, and spleen tissues in the autopsy of COVID-19 cases.

Objective:Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods:We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results:In the analysis,average levels of indoor PM with aerodynamic diameters＜2.5 μm(PM2.5)decreased significantly by 59.2％(from 59.6 to 24.3 μg/m3,P＜0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by-84.6％(95％confidence interval[CI]:-90.7 to-78.6),growth differentiation factor-15 by-48.1％(95％CI:-31.2 to-25.6),osteoprotegerin by-65.4％(95％CI:-56.5 to-18.7),interleukin-4 by-46.6％(95％CI:-62.3 to-31.0)and myeloperoxidase by-60.3％(95％CI:-83.7 to-3.0),respectively.Conclusion:Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable popu-lations at risks.

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