Objective To study the setup error under deep inspiration breath hold (DIBH) guided by optical surface monitoring system (OSMS) and free breathing (FB) FB1 and FB2 (without OSMS guidance, directly set up the body marker line by laser lamp) in radiotherapy after radical mastectomy for left breast cancer, and to provide a basis for individualized clinical target volume-planning target volume (CTV-PTV) expansion for the doctor in charge to delineate the target volume. Methods A total of 36 patients with left breast cancer after radical mastectomy were selected and divided into three groups, in which cone beam computed tomography (CBCT) images were taken in three states: DIBH, FB1, and FB2, respectively. CBCT and CT images were analyzed for registration; the absolute error data of linear displacement in the ventro-dorsal, cranio-caudal, and left-right directions were recorded, and the expanding margin was calculated. Results The translation errors in the ventro-dorsal, cranio-caudal, and left-right directions were (0.06 ± 0.22) cm, (0.05 ± 0.23) cm, and (0.01 ± 0.24) cm in the DIBH group, (0.07 ± 0.21) cm, (0.02 ± 0.23) cm, and (0.02 ± 0.21) cm in the FB1 group, and (0.07 ± 0.24) cm, (0.07 ± 0.34) cm, and (0.25 ± 0.09) cm in the FB2 group. The statistical results of the DIBH group and FB1 group in the ventro-dorsal, RTN, and ROLL directions were significantly different (P < 0.05). The statistical results of the FB1 group and FB2 group in the ventro-dorsal direction were significantly different. The relation of three groups in the value of margin of planning target volume was DIBH < FB1 < FB2 in the ventro-dorsal and cranio-caudal directions and FB1 < DIBH < FB2 in the left-right direction. Conclusion OSMS-guided DIBH radiotherapy in patients with left breast cancer after radical mastectomy can reduce the setup error and provide an important basis for individualized CTV-PTV expansion for the doctor in charge to delineate the target volume.

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 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.

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

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

AIM: To investigate the guiding role of individualized medication adjustment based on CYP2C19 metabolic typing in the treatment of ischemic stroke with clopidogrel, and to provide reference for clinical individualized medication. METHODS: The total of 80 patients with ischemic stroke were divided into the individualized drug instruction group with gene detection (n=40) and the control group without gene detection (n=40) according to whether they received CYP2C19 gene detection. According to the metabolism of CYP2C19, the individualized medication instruction group was divided into slow metabolic type, intermediate metabolic type, fast metabolic type and ultra-fast metabolic type. Patients with fast and ultra-fast metabolites were given clopidogrel dose of 75 mg once a day. Patients with intermediate metabolic type were given double clopidogrel dose of 150 mg once a day. Patients with slow metabolism were given tigrillo dose of 90 mg twice a day or aspirin dose of 100 mg once a day. The control group received 75 mg clopidogrel once a day. All patients enrolled in the groups were followed up for 3 months by outpatients or telephone. The incidence of vascular events and mRS scale scores were compared between the two groups. RESULTS: The incidence of vascular events in the individualized drug instruction group was significantly lower than that in the control group, and the incidence of mRS score(0-1) was significantly higher than that in the control group, with statistically significant differences (P<0.05). CONCLUSION: The individualized medication for patients with ischemic stroke by CYP2C19 gene detection can significantly reduce the incidence of adverse vascular events and improve the prognosis and living ability of patients.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection(ESD) for early hypopharyngeal carcinoma and precancerous lesions.Methods:Data of 23 patients with early hypopharyngeal carcinoma and precancerous lesions who underwent ESD in Sichuan Cancer Hospital from December 2015 to May 2019 were analyzed.Results:A total of 23 patients with 30 lesions were enrolled in the study. All patients were male, with mean age of 60.3 years (ranged 47-72). Of the 23 patients, 13 had synchronous esophageal cancer, 3 had metachronous esophageal cancer, and 7 high-grade intraepithelial neoplasia(HGIN) of the esophagus. The mean procedure time was 74 minutes. The en bloc resection rate was 100%. Pathological results revealed that 21 lesions were HGIN, 8 lesions were intramucosal carcinoma and 1 lesion had tumor invasion of the submucosa. Two patients had positive horizontal margin and 1 patient had positive vertical margin. The curative resection rate was 90%. No bleeding, perforation or dyspnea occurred during or after ESD.Conclusions:ESD is safe and effective for early hypopharyngeal cancer and precancerous lesions.

Objective: To evaluate the feasibility, safety and clinical value of endonasopharyngeal ultrasound-guided transnasopharyngeal needle aspiration (ENUS-TNNA) in the diagnosis of submucosal nasopharyngeal carcinoma. Methods: Clinical data of 9 patients from Sichuan Cancer Hospital with submucosal nasopharyngeal carcinoma undergoing ENUS-TNNA between December 2013 and January 2018 were retrospectively analyzed. The feasibility and safety were analyed. All 9 patients were all males with a mean age of (49.2±10.9) years. Results: Needle puncture biopsies were successfully performed in all cases, and sufficient tissue sample for histopathological examination was obtained from each of the 9 patients. No major bleeding or persistent bleeding occurred during and after puncture procedures. There were 5 patients with undifferentiated nonkeratinizing carcinoma and 4 patients poorly differentiated carcinoma. Conclusion ENUS-TNNA is a safe, feasible and effective technique to provide a diagnosis of submucosal growth type of nasopharyngeal neoplasms, which has some clinical value.

Objective To investigate the effect of warfarin on coagulation and hemorheology in patients with atrial fibrillation.Methods 106 cases of admitted in our hospital from October 2014 to October 2016 were randomly divided into observation group(53 cases)and control group(53 cases).The control group re-ceived routine treatment,the observation group received routine and warfarin treatment.The two groups were treated for 4 weeks.The therapeutic effects were compared between the two groups.Before and after treat-ment,indicators of heart function,blood coagulation and hemorheology were observed.Results The total effi-ciency of observation group(92.45%)was higher than that of the control group(73.58%,P<0.05).After treatment,the TT and APTT of the two groups both increased(P<0.05);The TT and APTT of the observa-tion group were higher than that of the control group(P<0.05);The plasma viscosity,erythrocyte aggrega-tion index,and fibrinogen of the two groups decreased(P<0.05);The plasma viscosity,erythrocyte aggrega-tion index,fibrinogen of the observation group were lower than that of the control group(P<0.05).Conclu-sion Warfarin has obvious curative effect on patients with atrial fibrillation,and can improve the function of blood coagulation and hemorheology.

Objective To establish a monkey model of muscle atrophy by fixing the right lower limb and set up e-valuation criteria for that model. Methods Twelve healthy,6-7 year old male cynomolgus monkeys(body weight 6-7 kg)were used in this study. All animals were normal and had no malformed lower limb bones. Right lower limbs of the an-imals were fixed with fiberglass bandage(from knee joint to anklebone)for 15 weeks. Body weight,crus perimeter and crus volume were recorded every two weeks. MRI examinations of the gastrocnemius muscle were conducted at weeks 11,13 and 15. Muscle biopsy was taken for pathological examination at week 15. Results There were no obvious changes of body weight during the experiment. At 15 weeks after modeling,the right crus perimeter and crus volume of the experimental an-imals were significantly decreased(P <0.05),and some biochemical indexes such as serum creatinine,gloucose and al-kaline phosphatase were significantly decreased(P <0.05), while cholesterol was significantly increased(P <0.05).MRI showed atrophy of the right gastrocnemius muscle. Muscle biopsy also showed muscle atrophy and muscle fibers be-came thinner in the right gastrocnemius,and the cross-section area of the muscle fibers was significantly decreased. Con?clusions It is easy to operate and establish a muscle atrophy model in Cynomolgus monkeys by fixing the right lower limb. This model is suitable for objective and easy evaluation of muscle atrophy by measurement of crus perimeter and crus volume of the limb,blood biochemical parameters,MRI examination,and histopathological examination in combination.