Small molecule drug screening technology is continuously evolving and expanding along with drug discovery,and the innovation in drug screening technology can improve the research and development efficiency and success rate,shorten the cycle time,and reduce the cost.From traditional screening technologies based on known active compounds and high-throughput screening(HTS)to new technologies such as structure-based drug discovery(SBDD),fragment-based drug discovery(FBDD),DNA encoded compound library(DEL)and proteolysis targeting chimeras(PROTAC),small molecule drug screening technologies are continuously broadening the market potential for small molecule drugs.This article will provide an overview of the current status of small molecule drug screening technology,systematically review each technique along with their advantages and disadvantages,and offer essential insights for the development of new small molecule drug screening technologies.

Objective:To study the changing trend of brucellosis epidemic in Taiyuan City, Shanxi Province from 2004 to 2022, and to provide reference for formulating brucellosis prevention and control policies.Methods:Through the China Disease Prevention and Control Information System, the epidemic data of human brucellosis with the onset time from January 1, 2004 to December 31, 2022 and the current address in Taiyuan City were collected. Descriptive epidemiological methods were used to analyze the temporal, regional, and population distribution characteristics of brucellosis.Results:From 2004 to 2022, a total of 1 834 cases of brucellosis were reported in Taiyuan City, with an average annual incidence rate of 2.25/100 000. The incidence rate of brucellosis in each year showed a fluctuating upward trend (χ 2trend = 428.04, P < 0.001). The onset time was mainly concentrated from February to August, accounting for 76.94% (1 411/1 834) of the total cases, with May being the peak month (283 cases). The incidence rate of brucellosis in all counties (cities and districts) ranged from 0 to 38.37/100 000, with the highest incidence rate in Loufan County in 2021. There were 1 470 males and 364 females, with a male-to-female ratio of 4.04 ∶ 1.00. The age range was 1 to 95 years old, among which the 1 - 29 age group accounted for 14.29% (262/1 834), the 30 - 39 age group accounted for 13.14% (241/1 834), the 40 - 49 age group accounted for 21.05% (386/1 834), the 50 - 59 age group accounted for 27.54% (505/1 834), and the 60 - 95 age group accounted for 23.99% (440/1 834). The main occupation was farmers and herdsmen, accounting for 67.23% (1 233/1 834). Conclusion:From 2004 to 2022, the epidemic of brucellosis in Taiyuan City shows a fluctuating upward trend, with males, middle-aged and elderly people, and farmers and herdsmen as the main affected population.

OBJECTIVE: Evidence that long-term exposure to ambient air pollution increases mortality among older adults, particularly those residing in low-level air pollution locations, remains scarce. This study investigated the potential links between long-term low-level air pollution exposure and mortality among Chinese older adults. METHODS: A population-based study with 317,464 individuals aged ≥ 65 years was conducted in Shenzhen, China during 2018 and 2020. Logistic regression models were used to analyze the associations between long-term exposure to air pollution and all-cause mortality, as the primary outcome, as well as non-accidental, cancer and cardiovascular mortality. RESULTS: Significant associations of PM ₁, PM _2.5, PM ₁₀, SO ₂, CO, and O ₃ exposures with a higher risk of all-cause mortality were found. Adjusted odds ratio ( OR) for each 1 µg/m ³ increment was 1.49 [95% confidence interval ( CI): 1.46, 1.53] for PM ₁, 1.30 (1.27, 1.32) for PM _2.5, 1.05 (1.04, 1.06) for PM ₁₀, 5.84 (5.39, 6.32) for SO ₂, 1.04 (1.04, 1.05) for CO, and 1.02 (1.00, 1.03) for O ₃, respectively. Long-term PM ₁, PM _2.5, PM ₁₀, SO ₂, and CO exposures also elevated the risks of non-accidental, cancer and cardiovascular mortality. CONCLUSION Long-term low-level air pollution exposure was associated with an increased mortality risk among Chinese older adults.
Humans ; Aged ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Air Pollutants/analysis* ; Aged, 80 and over ; Particulate Matter/adverse effects* ; Cardiovascular Diseases/mortality* ; Mortality ; Neoplasms/mortality* ; East Asian People

Objective:To analyze and summarize the implementation effect of basic essential surgical training (BEST) course of laparoscopic skills over the past 10 years and the practical experience in updating course content and models.Methods:The pre-class assessment questionnaires, basic laparoscopic operation assessment results, and post-class assessment questionnaires of the students who participated in the BEST course of laparoscopic skills were collected. According to the period of the course construction, the students were divided into two groups, namely students who used the course of single training system in the early stage (traditional group) and students who used the course integrating a variety of training systems after the course model was updated in the later stage (test group). The two groups were compared for the scores of track circle moving, tunnel crossing, and high and low columns, as well as their subjective evaluation of course setting and implementation effect. The t-test, Wilcoxon test, or chi-square test was conducted according to the data type using SPSS 13.0. Results:The time for 150 traditional group students to complete track circle moving, tunnel crossing, and high and low columns was 1.08 min (0.81 min, 1.60 min), 2.20 min (1.60 min, 3.27 min), and 4.86 min (3.28 min, 6.36 min), respectively, while the time for 75 test group students to complete the three operations was 1.27 min (0.87 min, 1.83 min), 2.57 min (1.58 min, 4.07 min), and 4.35 min (2.90 min, 6.42 min), respectively, with no significant difference between the two groups ( P>0.05). In terms of students' subjective evaluation of the course, a higher percentage of the test group students were satisfied with classroom environment, teaching method arrangement, training equipment, training opportunities, helping clinical work, and meeting pre-class expectations than those in the traditional group. Conclusion:The constantly updated BEST course can ensure the training quality of trainees and obtain their higher satisfaction. The benefits of this course in clinical practice can be further verified through long-term follow-up of these trainees.

Virtual reality (VR) is a technology that interacts computer-generated three-dimensional scenes with the user′s senses and has been gradually applied in the real medical field. Since the first time of successful attempt in 3D laparoscopic gastrointestinal surgery VR living video broadcast in 2016, the authors have experienced the exploration of the application of this technology (2016-2017) as well as the in-depth research phase (2018-2019). Nowadays, the VR application in our center has entered into the application practice phase (2020 to present). With the technology iteration and more and more application experience acquisition, our current VR application mainly focuses on two practice settings, including the clinical teaching scenarios for early exposure to acute appendicitis for medical undergraduate students and the preoperative communication to give pati-ents an early sense of the process in the operating theatre, and has achieved good application results. With continuous breakthroughs and innovations in software and hardware, we believe that more clinical VR scenarios and the course audience will be expanded to a wider group. The integration of some new hotspots such as Meta-Universe and ChatGPT will make up for the shortcomings in VR content scenarios and interactivity, and its application prospects are infinite.

OBJECTIVE To explore the role of the establishment of the trans-regional review system on rational drug use in second-grade general hospital ，and to promote the rational drug use. METHODS With the administrative support of Jiuquan Health Commission，5 second-grade general hospitals in Jiuquan Medical Association jointly established Jiuquan Rational Drug Use Review Training Center . A trans-regional review system was established to carry out cross-review of prescriptions and medical orders among 5 second-grade general hospitals. Totally 1 500 prescriptions and 900 medical records were collected from 5 second-grade general hospitals before （April to June ，2020）and after （July to September ，2020）the implementation of the project. The changes of rational drug use indicators ，the results of prescriptions and medical order review were investigated before and after the implementation of the project. RESULTS After the implementation of the project ，except for one hospital ，the proportion of drugs in other hospitals decreased to varying degrees with the highest decline rate of 22.56％ . Compared with before the implementation of the project ，reasonable rate of outpatient and emergency prescription review increased by 5.72％ averagely and the reasonable rate of medical order review increased by 10.10％（P＜0.05）. The average utilization rate of antibiotics in outpatients decreased by 14.45％，the average utilization rate of antibiotics in inpatients decreased by 7.98％，and the average use intensity of antibiotics decreased by 25.19％. CONCLUSIONS Through the establishment of trans-regional review system ，medical institutions can be forced to pay more attention to prescription review ，effectively improve the prescription review of pharmacists in medical institutions，and promote the rational use of drugs in medical institutions in the region. However ，there are still some problems ， such as incomplete system coverage ，insufficient work experience ，lagging of informatization ，uneven pharmacist level ，and insufficient assessment and supervision of administrative functional departments.

Objective To analyze the role of lienal polypeptide injection in acute lung injury induced by lipopolysaccharide (LPS) in rats. Methods Eighty male SD rats were randomly allocated into 4 groups: a LPS group, a control group, a lienal polypeptide group and a LPS+ lienal polypeptide group (20 rats in each group). Lienal polypeptide or normal saline was given with an intramuscular injection 30 min after an intraperitoneal injection of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 4 h after LPS challenge by enzyme-linked immunosorbent assay (ELISA), wet-to-dry weight ratio, hematoxylin and eosin (HE) staining, TUNEL and Western blotting. Results Lienal polypeptide injection treatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. Moreover lienal polypeptide injection significantly suppressed LPS-induced activation of metastasis-associated protein-1 (MTA1). Conclusion Lienal polypeptide injection is demonstrated to protect rats from LPS-induced acute lung injury by the expression of MTA1.

Objective To evaluate the clinical value of Chinese Multi-Dimensional Health Assessment Questionnaire (MDHAQ-C) in patients with rheumatoid arthritis (RA). Methods From December 2015 to October 2016,four hundred and twelve RA patients were recruited in this study and completed the MDHAQ-C independently and routine assessment of patient index data 3 (RAPID3) was calculated. Then correlations were assessed by Spearman correlation coefficient of RAPID3 with indices of clinical relevance and disease activity to evaluate its clinical values. Results MDHAQ-C is moderately correlated with ESR (r=0.399), CRP (r=0.381), SJC (r=0.499), TJC (r=0.558) (P<0.01), but highly correlation with VAS of pain (r=0.836), VAS of global status (r=0.915) and overall assessment of physician (r=0.784)(P<0.01), and highly correlated with a Spearman's coefficient of 0.784 for DAS 28-ESR, 0.734 for CDAI and 0.682 for SDAI (P<0.001). Conclusion MDHAQ is a reliable, valid instrument for disease activity assessment and a feasible index for clinical settings in Chinese RA patients.

Objective To assess the effect of thoracoscopic surgery under laryngeal mask anesthesia and explore the nursing strategies. Methods Thirty-five patients from April to December in 2014 undergoing video-assisted thoracoscopic surgery (VATS) were given intubation anesthesia and another thirty-five ones undergoing the same surgery in 2015 received laryngeal mask anesthesia. The two groups were compared in terms of surgery conditions, surgery complication and ambulation time. Results No significant differences were found in surgery time or blood loss between two groups (P>0.05). The postoperative waking time in the mask anesthesia group was significantly shorter than that of the intubation anesthesia group (P<0.05), and ambulation time was significantly shortened (P<0.05). The rates of throat discomfort, hoarseness and gastrointestinal reactions were significantly lower. Conclusions Laryngeal mask anesthesia used in small thoracoscopic surgery for airway management is safe and feasible. Combined with training in respiration and limb function, better analgesia and nursing, it can keep away complications related to intubation anesthesia, shorten hospital stay and accelerate postoperative rehabilitation.

Objective To find a new method for evaluating the left ventricular relaxation time constant Tau with aortic regurgitation by continuous wave Doppler.Methods Twelve Beagle dogs were included in the study.The dog aortic regurgitation model was produced under ultrasound guiding by carotid artery puncture.Aortic pressure was measured by pressure catheter and left ventricular pressure was measured by Millar catheter which was introduced into the left ventricular through cardiac apex.Then microspheres were injected into the left coronary artery under the guidance of ultrasound to induce acute ischemic left ventricular dysfunction,when left ventricular end-diastolic pressure increased more than 5 mmHg (1 mmHg=0.133 kPa).Dobutamine or esmolol was infused to alter left ventricular function.Aortic regurgitation velocity spectrum was recorded by the continuous-wave Doppler echocardiography in different hemodynamic status.At the same time,left ventricular pressure,dp/dt,aortic pressure and continuous ECG tracing were displayed on the multi-channel physiological recorder.Measurement was recorded of-dp/dtmax in the dp/dt tracings and the pressure at the time of-dp/dtmax in the left ventricular pressure tracings.Tau =-P/(dp/dtmax),Tau was the catheter-derived time constant (Taucatheter).Aortic regurgitation spectrum of original audio data was post-processed with MATLAB mathematical software.The spectral lines refresh time of about 300 μs was chosen to form a new Doppler spectrum.Three points:(t1,1 m/s),(t2,2 m/s) and (t3,3 m/s) were selected in aortic regurgitation velocity spectrum and tl,t2 and t3 was put into the corresponding Tau formula:Tau=(t2-t1)/ln[(ADP-C-4)/(ADP-C-16)],Tau=(t3-t1)/ln[(ADP-C-4)/(ADP-C-36)].Tau was the aortic regurgitant time constant (Tauultrasound).The difference between Taucatheter and Tauultrasound was compared by paired t test.The correlation between Taucatheter and Tauultrasound was analyzed by Pearson correlation analysis.Results Twelve dogs were successfully produced aortic regurgitation model.Two dogs died of ventricular fibrillation during the procedure of acute ischemic left ventricular diastolic dysfunction.The range of the Taucatheter was between 27.12 ms and 86.88 ms with an average of (48.973± 14.667) ms;the range of the Tauultrasound was between 28.13 ms and 90.18 ms with an average of (51.236± 15.146) ms.The difference was not statistically significant (t=1.841,P ＞ 0.05).Pearson correlation analysis showed that Taucatheter was positively correlated with Tatultrasound (r=0.89,P=0.000).Conclusion Choosing three points:(t1,1 m/s),(t2,2 m/s) and (t3,3 m/s) in aortic regurgitant velocity spectrum and putting into the corresponding formula,we can calculate Tau,which had a good correlation with the catheter-derived Tau.