Cytochrome P450 family 3 subfamily A(CYP3A),a major member of cytochrome P450(CYP)family,is one of the most important drug metabolizing enzymes in human.CYP3A includes 4 gene subtypes(CYP3A4,CYP3A5,CYP3A7,and CYP3A43),which is involved in 60%of drug metabolism in the human.It is not only widely distributed in normal tissues,but also significantly overexpressed in various tumor tissues.Recently,CYP3A has attracted great attention due to its involvement in the progression from chronic atrophic gastritis to gastric cancer,as well as the differential metabolism and resistance of chemotherapeutic drugs.Targeting CYP3A gene mediated-prodrug provides new ideas for the treatment of gastric cancer and is expected to become a new target for the diagnosis and treatment of gastric cancer.

Accurate classification of the acetabular injuries and appropriate treatment plan are great challenges for orthopedic surgeons because of the irregular anatomical structure of the acetabulum and aggregation of important vessels and nerves around it. Letournel-Judet classification system has been widely applied to classify acetabular fractures. However, there are several limitations, including incomplete inclusion of fracture types, difficulty in understanding and insufficient guidance for surgical treatment, etc. Serious complications such as traumatic arthritis are common due to wrong classification and diagnosis and improper selection of surgical strategy, which brings a heavy burden to the society and families. Three-column classification, based on anatomic characteristics, has advantages of containing more fracture types and being easy to understand, etc. To solve the problems existing in the diagnosis and treatment process based on Letournel-Judet classification, achieve accurate diagnosis and treatment of patients with acetabular fractures, and obtain satisfactory prognosis, the Orthopedic Trauma Emergency Center of Third Hospital of Hebei Medical University and the Trauma Orthopedic Branch of the Chinese Orthopedic Association organized experts from relevant fields to formulate the Expert consensus on the accurate diagnosis and treatment of acetabular fractures based on three-column classification ( version 2023) in terms of principles of evidence-based medicine. Based on the three-column classification, 15 recommendations were proposed, covering the diagnosis, treatment, complication prevention and management, etc, so as to provide reference for accurate diagnosis and treatment of acetabular fractures.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

ObjectiveTo apply resting-state functional magnetic resonance imaging in acute mild traumatic brain injury. MethodsFrom May, 2019 to May, 2021, 47 cases with acute mild traumatic brain injury in Beijing Bo'ai Hospital were selected as observation group, and 50 healthy people who visited for routine physical examination during the same period were as control group. They were scanned with resting-state functional magnetic resonance imaging to measure amplitude of low-frequency fluctuation (ALFF), and they were assessed with Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Rivermead Behavioural Memory Test (RBMT). ResultsCompared with the control group, the scores of MMSE, MoCA and RBMT decreased in the observation group (t > 18.138, P < 0.001); while ALFF decreased in the brain areas of posterior cerebellar lobe, cerebellar tonsils, lower half moon lobules, right superior temporal gyrus, right middle temporal gyrus, right parietal lobe and right central posterior gyrus, etc; and ALFF increased in the brain areas of marginal lobe, cingulate gyrus, precuneus, left cerebellar, right superior temporal gyrus, right middle temporal gyrus, right superior frontal gyrus, right middle frontal gyrus, right inferior frontal gyrus, etc. ConclusionThere are disorders in multiple brain areas for patients after acute mild traumatic brain injury, which may associate to the cognitive impairment.

Objective:To investigate the antimicrobial properties of copper-loaded coatings on the surface of ureteral stents and their biocompatibility in order to determine the most suitable level of copper loading.Methods:Copper-loaded PDA coatings with different copper contents were constructed on the surface of polyurethane (PU) stents using polydopamine (PDA) and dimethylaminomethylborane (DMAB). The antibacterial property of the coating against Escherichia coli and Staphylococcus aureus was investigated by the plate counting method. The bacterial adhesion on the coating surface was studied by scanning electron microscopy. Using the live/dead evaluation, microbes were stained and observed by a fluorescence microscope. The biocompatibility of the copper-loaded coatings was detected by a cell proliferation assay incubated with L929 cells.Results:The antibacterial rates of the copper-loaded samples exceeded 90% after incubation with E. coli and S. aureus for 24 h, respectively, and the antibacterial performance increased with the increase of copper content in the coating. The amount of bacteria adhered to the surface of the copper-loaded samples was significantly lower, and most of them were dead bacteria. When the copper content in the coating preparation solution used was 0.25~1 g/L, the cell proliferation rate on the surface of the copper-loaded coating was higher than 80% and the material was not cytotoxic.Conclusions:A copper-loaded PDA coating with excellent antibacterial properties and good biocompatibility can be prepared with a copper content of 1 g/L in the coating preparation solution, forming a potential solution for the preparation of ureteral stent coatings.

Objective:To explore the effect of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive behavioral therapies (CBT) on the cognitive function and alcohol craving in patients with alcohol dependence.Methods:From March 2019 to September 2021, a total of 150 patients with alcohol dependence were enrolled and randomly divided into rTMS treatment group (rTMS+ sham CBT, n=41), CBT treatment group (CBT+ sham rTMS, n=34), rTMS+ CBT treatment group( n=36) and control group (sham rTMS+ sham CBT, n=39). At baseline (before treatment), 2nd week, 8th week, 12th week and 24th week, alcohol dependence scale (ADS) was used to evaluate the degree of alcohol dependence, the obsessive compulsive drinking scale (OCDS) was used to assess patients' drinking craving, and Montreal cognitive assessment scale (MoCA) was used to assess the overall cognitive level of patients.SPSS 23.0 statistical software was used to compare the differences of ADS, OCDS and MoCA scale scores of the four groups by repeated measure ANOVA and simple effect analysis. Results:(1)The patients in the four groups were evaluated with ADS scale at baseline, 12th week and 24th week respectively.The interaction of group×time( F=1.279, P=0.279) and the main effect of group were not significant ( F=0.882, P=0.454), and the main effect of time was significant ( F=12.925, P<0.001) .Further simple effect analysis showed that the ADS score of rTMS+ CBT group was lower than that of baseline(14.48±5.70, 10.00±6.51) ( P=0.01) at 24th week.(2)Patients in the four groups were assessed with OCDs scale at baseline, 2nd week, 8th week, 12th week and 24th week, and the interaction of group×time was significant ( F=2.015, P=0.042). Further simple effect analysis showed that the OCDs scores of rTMS group and rTMS+ CBT group at each follow-up time node were lower than those at baseline period (all P<0.05). (3)Patients in the four groups were assessed with MoCA scale at baseline, 8th week, 12th week and 24th week, and the interaction of group×time was not significant ( F=1.660, P=0.106), and the main effect of group and the main effect of time were significant ( F=2.964, P=0.038; F=14.239, P<0.001). Further simple effect analysis showed that the score of MoCA scale in CBT group at the 24th week was higher than that at baseline (21.73±5.81, 24.60±3.98)( P=0.029), the score of MoCA scale in rTMS+ CBT group at the 24th week was higher than that at the 8th week (23.50±6.01, 25.95±2.87) ( P=0.006), and the score of MoCA scale in rTMS group at the 12th week was higher than that in control group (22.08±6.64, 26.64±2.46)( P=0.009). Conclusion:rTMS combined with CBT can be effective in improving alcohol craving and cognitive function in patients with alcohol dependence, and has a good long-term effect.

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
Humans ; Kidney ; Organoids ; Pluripotent Stem Cells

ObjectiveTo analyze the mental health status and the influencing factors among the residents taking standardized residency training during the outbreak and stable period of COVID-19， so as to provide theoretical basis for their mental health education. MethodsOn February 8 to February 10 and April 11 to April 13， 2020， Symptom Checklist 90 （SCL-90）， Beck Srivastava Stress Inventory （BSSI） and Simplified Coping Style Questionnaire （SCSQ） were distributed in online chat groups involving all grades of residents taking standardized residency training in the Second Affiliated Hospital of Kunming Medical University. Through two rounds of questionnaire survey， non-probability sampling method was used to obtain survey samples， and their mental status were analyzed. ResultsA total of 159 valid questionnaires were collected in the first round， and 99 valid questionnaires in the second round. The first survey showed that the total score of SCL-90 was （117.69±37.74） and the detection rate of positive symptoms in SCL-90 was 25.8%， and mainly dominated by obsession， fear and interpersonal sensitivity. In the second survey， the results showed that the total score of SCL-90 was （127.19±51.44）， and the main positive symptoms included obsession， depression and interpersonal sensitivity， with a positive detection rate of 30.3 %. The first survey found that the mental health status had significant differences among residents of different grades （χ²=7.46， P<0.05）， furthermore， the results indicated that lower grade was a risk factor while non-singleton was the protective factor of mental health status （P<0.05）， and SCL-90 total score was positively correlated with score of negative coping styles （r=0.45， P<0.01）. The second survey also classified lower grade as risk factor and non-singleton as protective factor （P<0.05）， and SCL-90 total score was positively correlated with study stress， economic pressure， interpersonal relationship， clinical practice and negative coping styles （r=0.52， 0.46， 0.55， 0.54， P<0.05 or 0.01）. ConclusionResidents under standardized residency training have obvious mental health problems during the outbreak of COVID-19， and the problems become more serious during the stable period of COVID-19.

Objective:To summarize the experience of radiation oncology residency training programs in western coutries, and provide evidence to improve the present Phase-I Radiation Oncology Residency Training Programs in China.Methods:An electronic questionnaire-based survey was conducted among residents and staffs in 6 top cancer centers in China and 5 centers from Europe and North America to collect their feedback regarding the description and comparison of different programs.Results:A total of 70 responses and 4 papers explaining relevant training programs from 26 residents and 23 teachers in Chinese hopsitals and 20 residents and 1 teacher from Europe and North America were received. The Radiation Oncology Residency Training Programs in China were designed into 2 phases, and the results in the current study were involved with the first phase. Program designs were similar in the following aspects: goal, clinical practice-based training, rotation curriculum, interim and final assessment. However, the total timeframe in the investigated Chinese Phase-I programs was shorter than that in western hospitals (2 to 3 years vs. 4 to 5 years). Chinese programs covered major common diseases, whereas rotation design was performed based on each individual disease in western programs. In Chinese programs, the working hours were mainly 40-60 h every week. Although the working hours were commensurate with local workforce regulations, the residents from MSK program had an outstanding longer working time of 60-80 h every week and treated more patients compared with other programs. Conclusions:The investigated Phase-I Radiation Oncology Residency Training Programs in 6 top cancer centers in China share common features in goals, training modes and assessments with western programs. However, our programs have shorter timeframe and less detailed requirements in individual disease than the western programs.

Objective:To investigate the characters and emergency treatment strategy of upper urinary tract stone obstruction complicated with urosepsis.Methods:Clinical data of 28 cases of urosepsis, caused by upper urinary tract stone obstruction and arranged for emergency admission in our hospital during January 2018 to December 2019, were retrospectively analyzed. There were 6 males and 22 females. The median age was 54(32-93)years old. All patients had fever with the temperature ranged from 38.5 to 41.0 ℃. The median course of disease was 3 (ranging 1-14) days. The systolic blood pressure ranged from 76 to 138 mmHg at admission. Hypotension group was defined as the systolic blood pressure<90 mmHg after admission. Normotensive group was defined as the systolic blood pressure≥90 mmHg. There were 12 cases in hypotension group, including 3 males and 9 females. The median age was 57 (ranging 32-93) years old. The stones located at left side in 7 cases and right side in 5 cases. The stones located at the upper ureter in 5 cases, middle ureter in 2 cases, lower ureter in 4 cases and renal calculi in one case. The median length of the stone was 10 (ranging 6-20) mm. Six cases suffered with diabetes mellitus. One case suffered with neuron system disease. 3 cases have history of recent extracorporeal shock wave lithotripsy(ESWL). There were 16 cases in normotensive group, including 3 males and 13 females with the median age of 53 (ranging 33-76) years old. The stones located at left side in 5 cases, right side in 9 cases and bilateral in 2 cases. The stones located at the upper ureter in 10 cases, middle ureter in 4 cases, lower ureter in 2 cases. The length of the stone was 10 (ranging 8-14) mm. There were 3 cases with neurological diseases and 3 cases with recent ESWL history. There was significant difference between hypotension group and normotensive group in ration of diabetes mellitus ( P=0.024). Blood routine examination, C-reactive protein (CRP), procalcitonin(PCT), blood and urine bacterial culture were performed in both groups. The patients were treated with empiric antibiotics after the evaluation based on the sequential organ failure assessment (SOFA). Patients with hypotension were given blood volume expansion, and vasoactive drugs were added when the blood pressure was still low. After the blood pressure was stable, the collection system decompression was performed. The difference of infection indicators and therapeutic methods between the two groups was compared. Results:There was no significant difference in median WBC [16.34 (2.55-41.65) × 10 9/L vs. 13.97(6.23-26.65) × 10 9/L, P=0.577], median CRP [143.0(74.2-200.0) ng/ml vs.110.0 (22.7-200.0) ng/ml, P=0.771] between hypotension group and normotensive group. The difference of PCT [95.5 (26.5-200.0) ng / ml vs. 57.6 (1.0-200.0) ng / ml, P=0.040] and PLT [65.5(14.0-170.0)×10 9/L vs. 73.0(17.0-412.0)×10 9/L, P=0.030] between hypotension group and normotensive group was statistically significant. The median SOFA scores of hypotension group and normotensive group were significantly different [8.5(3.0-13.0) vs. 5.0(2.0-8.0), P=0.001]. Ureteral stent placement was performed in 23 cases, and nephrostomy was performed in 5 cases. There was no significant difference in surgical drainage between the two groups ( P=0.887). Eight patients in hypotension group were admitted to ICU. There was no significant difference in the duration of antibiotic use between hypotension group and normotensive group [8 (3-12) d vs. 5 (3-7) d, P=0.453]. Sepsis was cured in both groups after decompression, fluid resuscitation and antibiotic treatment. Conclusions:In severe cases of upper urinary tract stone obstruction complicated with urogenic sepsis, septic shock may occur. The condition is urgent, severe and dangerous. Patients with hypotension had higher PCT and SOFA scores, and lower PLT. It is very important to carry out the collection system decompression drainage in time, liquid resuscitation, early effective antibiotic use.