Accurate prediction of drug responses in cancer cell lines (CCLs) and transferable prediction of clinical drug responses using CCLs are two major tasks in personalized medicine. Despite the rapid advancements in existing computational methods for preclinical and clinical cancer drug response (CDR) prediction, challenges remain regarding the generalization of new drugs that are unseen in the training set. Herein, we propose a multimodal fusion deep learning (DL) model called drug-target and single-cell language based CDR (DTLCDR) to predict preclinical and clinical CDRs. The model integrates chemical descriptors, molecular graph representations, predicted protein target profiles of drugs, and cell line expression profiles with general knowledge from single cells. Among these features, a well-trained drug-target interaction (DTI) prediction model is used to generate target profiles of drugs, and a pretrained single-cell language model is integrated to provide general genomic knowledge. Comparison experiments on the cell line drug sensitivity dataset demonstrated that DTLCDR exhibited improved generalizability and robustness in predicting unseen drugs compared with previous state-of-the-art baseline methods. Further ablation studies verified the effectiveness of each component of our model, highlighting the significant contribution of target information to generalizability. Subsequently, the ability of DTLCDR to predict novel molecules was validated through in vitro cell experiments, demonstrating its potential for real-world applications. Moreover, DTLCDR was transferred to the clinical datasets, demonstrating satisfactory performance in the clinical data, regardless of whether the drugs were included in the cell line dataset. Overall, our results suggest that the DTLCDR is a promising tool for personalized drug discovery.

Objective To explore the mediating effect of facial emotion recognition on prosocial behavior of medical students in mask-obscured scenes.Methods Fifty-three medical students from a medical university in Chongqing were enrolled from July to September 2023 to complete the facial emotion recognition task,the dictator gaming task and the state empathy test.Spearman correlation analysis was used to examine the correlation between mask wearing and state empathy,trait empathy and prosocial behaviours,and the PROCESS procedure was used to test the mediation of state empathy and the moderating effect of mask wearing or not.Results ①mask wearing,state empathy and prosocial behaviour were significantly correlated(P＜0.01);② State empathy exerted mediated effect between facial emotion recognition and prosocial behavior,with the largest effect size(47％)for the relative mediating effect of sadness;③The interaction terms of facial emotion recognition and mask wearing had a significant effect on state empathy(P＜0.05).Conclusion Facial emotion recognition can influence prosocial behavior directly and also exert indirect effect on prosocial behavior through state empathy.Compared to the condition without mask wearing,mask wearing can significantly facilitate the effect of happy,sad and neutral emotions on state empathy.

This case report presents an adolescent patient with type 3 pseudotumor associated with vascular hemophilia (von willebrand disease, VWD) of the femur. The patient experienced weakness and pain in the right knee joint for two months following physical activity, with no apparent history of trauma. Genetic testing identified two compound heterozygous mutations in the von willebrand factor (VWF) gene, consistent with a diagnosis of "VWD type 3". Laboratory results revealed a Factor VIII activity of 2.8%, a negative Factor VIII inhibitor test, VWF activity of 1%, and VWF antigen levels below 3%. The desmopressin infusion test (1 hours and 4 hours) showed VWF levels of less than 1%. Imaging studies revealed an osteolytic lesion in the right distal femoral epiphysis, characterized by discontinuous cortical resorption in the anterior femur, thinning of the medial, lateral, and posterior cortex, prominent sclerotic bands, and extension of the tumor into the distal femoral epiphysis without periosteal reaction. After multidisciplinary consultation, the diagnosis of VWD type 3 pseudotumor of the femur was confirmed. The patient had no history of coagulation factor supplementation and no significant knee trauma. Preoperatively, the VWF level was maintained above 80% with cryoprecipitate infusion. The lesion was surgically debrided, followed by bone grafting with autologous fibula and allograft bone. Postoperative follow-up at 5 months showed good recovery of knee function. Pseudotumor is a rare but serious manifestation of inherited bleeding disorders, predominantly observed in hemophiliacs. Skeletal muscle system pseudotumor in VWD is exceptionally rare, with previous reports limited to the maxilla and mandible. MRI is crucial for the diagnosis of hemophilic pseudotumor, with characteristic findings of peripheral enhancement without central enhancement on enhanced scans. Surgery remains the preferred and effective treatment, with adequate perioperative preparation being essential for success. In this case, a multidisciplinary approach was critical in developing a personalized treatment plan, contributing significantly to the patient's positive outcome.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Dopamine D₃ receptor (D₃R) is implicated in multiple psychotic symptoms. Increasing the D₃R selectivity over dopamine D₂ receptor (D₂R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D₃R selective ligands. Through a structure-based virtual screen, ZLG-25 (D₃R K_i = 685 nmol/L; D₂R K_i > 10,000 nmol/L) was identified as a novel D₃R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D₃R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD₃R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.

Objective    To evaluate the clinical effects of segmentectomy versus lobectomy under single utility port video-assisted thoracic surgery on inflammatory factors and immune cells in peripheral blood of non-small cell lung cancer patients, and to analyze the effect of changes of postoperative inflammatory factors and immune cells on the prognosis of the patients. Methods    The clinical data of 256 patients who underwent segmentectomy or lobectomy under single utility port video-assisted thoracic surgery for non-small cell lung cancer in the First Affiliated Hospital of Hebei North University from January 2016 to October 2020 were retrospectively collected. According to the operation method, they were divided into a segmentectomy group (126 patients with 79 males and 47 females at an age of 63.4±6.2 years) and a lobectomy group (130 patients with 91 males and 39 females at an age of 62.9±5.6 years). The change of inflammatory factors (C reactive protein, interleukin-6, interleukin-8, tumor necrosis factor-α) and immune cells (CD4+T cells, CD8+T cells and natural killer cells) were recorded and analyzed before operation (T0) and 1 day (T1), 3 days (T2), 7 days (T3), 1 month (T4) after the operation between the two groups. According to postoperative recurrence situations, they were divided into a recurrence group and a non-recurrence group, multivariate logistic regression analysis was used to analyze the relationship between the change of postoperative inflammatory factors, immune cells, and the prognosis of patients with non-small cell lung cancer. Results    (1) There was no statistical difference in sex ratio, underlying diseases, body mass index, levels of preoperative inflammatory factors or immune cells between the two groups (all P>0.05). (2) The changes of postoperative inflammatory factors in the segmentectomy group were significantly less than those in the lobectomy group at T1-T3 (all P<0.05), and the changes of postoperative immune cells in the segmentectomy group were significantly less than those in the lobectomy group at T1-T4 (all P<0.05). (3) The changes of postoperative inflammatory factors and immune cells on postoperative day 3 in the recurrence group were significantly more than those in the non-recurrence group (all P<0.05). (4) Multivariate logistic regression analysis showed that the changes of postoperative inflammatory factors and immune cells on postoperative day 3 may be the risk factors for postoperative recurrence and metastasis in patients with non-small cell lung cancer (all P<0.05). Conclusion    Single utility port video-assisted thoracic surgery segmentectomy for the treatment of non-small cell lung cancer can reduce the inflammatory response and protect body's immune function, and the change of postoperative inflammatory factors and immune cells in postoperative day 3 may be the risk factors for postoperative recurrence and metastasis in patients with non-small cell lung cancer.

Objective:To study the personality development of obsessive-compulsive disorder (OCD) from the perspective of memory-tracing.Methods:From January 2016 to May 2017, totally 103 patients with OCD (patient group) and 88 normal subjects (control group) matched with age, gender, and educational level in the national urban population norm database of Wang Weidong memory-tracing personality developmental inventory (WMPI) were included.WMPI was used to evaluate and compare all subjects.SPSS 22.0 software and nonparametric test were used for statistically analysis, and independent sample t-test and nonparametric test were used for data camparison. Results:1.In terms of external influencing factors of personality development: on the part of life events, the score of family affair in the patient group was higher than that in the control group( P<0.05) in childhood.In terms of upbringing, the scores of strictness (5.637±3.463) and punishment (6.275±4.565) in the patient group were higher than those ((4.341±3.092), (5.000±3.698)) in the control group in childhood( t=-2.703, -2.093, both P<0.05). 2.In the aspect of personality elements: (1) Among courage subscales, the scores of natural fear (7.686±3.441) and adaptability (15.000±5.321) in the patient group were higher than those((6.023±3.991), (12.841±6.070)) in the control group in childhood ( t=-3.085, -2.613, both P<0.05) .For all three stages, interpersonal fear scores in the patient group ((20.284±8.255), (22.804±7.458), (22.725±7.145))were all higher than those ((16.205±7.937), (19.841±6.319), (18.364±6.277))in the control group( t=-3.458, -2.929, -4.437, P<0.01). (2) Among interpersonal relationship, the dependence dimension scores were higher in the patient group (10.804±3.621) than those (8.830±4.850) in the control group during childhood( t=-3.205, P<0.01). (3) Among sex development, the scores of heterosexual communications (11.941±4.878), love concept (15.098±4.180) and sexual concept (8.892±2.988) were higher in the patient group than those ((9.125±5.040), (11.761±5.202), (6.943±3.288)) in the control group in adolescence(all P<0.01). (4) Among ego, the score of self-care dimension in the patient group (6.465±2.890) was higher than that in the control group(4.239±2.861) in childhood ( P<0.01). In the dimension of autonomy, the scores of the patient group ((10.772±2.694), (11.347±2.621)) were higher than those in the control group ((8.011±4.039), (9.818±2.693)) in childhood and adolescence (both P<0.01). (5) Among the way of thinking, the score of absolute thinking dimension in the patient group was higher than that in control group in childhood ( P<0.01). In the dimension of cautious, the scores of patient group were higher than those in the control group in childhood and adolescence (both P<0.01). (6)Among volition, the scores of decisive dimension in the patient group were higher than those in the control group in adolescence and youth (both P<0.01). In the dimension of consciousness, the score of patient group was higher than that in the control group in youth( P<0.01). In the dimension of insistence, the score of the patient group were higher than those in the control group in childhood and youth (both P<0.01). (7) Among worldviews, the scores of motivations, perspective of career and perspective of friendship in the patient group were higher than those in the control group in adolescence (all P<0.01). The score of value dimension in patient group was lower than that in the control group in the youth ( P<0.01). Conclusion:Patients with OCD have more strictness and punishment during their childhood in terms of upbringing.This leads to a lack of courage, poor interpersonal relationships, low self-care or autonomy, high attachment, absolutization of thinking and suppressing themself more in their childhood.In their adolescence and youth, their lack of courage, poor self-care or autonomy and the way of thinking cautious and stubborn will further aggravate and gradually show a more conservative sexual development and traditional world outlook.

Objective To establish an online quantitative analysis model for moisture content assay of hydroxychloroquine sulfate particles by near infrared (NIR) spectroscopy. Methods The NIR spectra were collected in real time when the material particles were dried in the fluidized bed. Meanwhile the water content of the particles was measured with the standard moisture tester. The multiplicative signal correction (MSC) and first derivative followed by Karl Norris smoothing were used for spectra pretreatment. Two spectral range (4 935−5 336 cm⁻¹ and 6 911−7 297 cm⁻¹) were selected for the quantitative model with the partial least squares (PLS) regression. Results The quantitative calibration model had good correlation coefficients with Rc value=0.952 9 and Rp value=0.936 6. The root mean square error of calibration (RMSEC) was 0.408 and the root mean square error of prediction error (RMSEP) was 0.435. The ratio of standard deviation of validation set to prediction standard deviation (RPD) was 5.18. There was no significant difference between the predicted value and the reference value by t test when the established model was applied in large-scale production. Conclusion The online model established for monitoring water content has high accuracy and stability, which can be applied in industrial scale process to monitor the particle moisture in real time.

Anoctamin 1 (ANO1) is a kind of calcium-activated chloride channel involved in nerve depolarization. ANO1 inhibitors display significant analgesic activity by the local peripheral and intrathecal administration. In this study, several thiophenecarboxylic acid and benzoic acid derivatives were identified as novel ANO1 inhibitors through the shape-based virtual screening, among which the 4-arylthiophene-3-carboxylic acid analogues with the best ANO1 inhibitory activity were designed, synthesized and compound