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.

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

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.

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 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.

Objective:To explore the effect of low frequency magnetic stimulation on myelin and inflammation in the callosum of demyelinated mice.Methods:Thirty-six 6 to 8-week-old male C57BL/6J mice were randomly divided into a control group, a cuprizone (CPZ) group and a magnetic therapy group. The CPZ group and the magnetic therapy group had demyelination induced by feeding a mixed diet containing 0.3% CPZ for 6 weeks, while the control group was given conventional food. The magnetic therapy group was given 50Hz 10mT magnetic stimulation during the 6 weeks for 20min daily, 5 days a week. The body mass of each mouse was observed every 7 days. At the end of the 6th week elevated cross maze experiments were conducted to observe any anxiety state. The myelin sheath in the corpus callosum was observed using Luxol fast blue staining and myelin basic protein (MBP) immunohistochemistry Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the corpus callosum were detected using enzyme-linked immunosorbent assays.Results:After the 6 weeks of treatment, the average body mass of the mice in the magnetic therapy group had improved significantly compared with the CPZ group. The CPZ group′s times in the elevated cross maze experiments were significantly shorter than those of the control group and also shorter than those of the magnetic therapy group. The Luxol staining showed significant myelin loss in the corpus callosum of the CPZ group, but compared with the CPZ group the average loss of myelin in the magnetic therapy group was significantly less. This was further confirmed by the MBP immunohistochemistry. Compared with the control group, the average expression of MBP in the CPZ group was significantly reduced, while in the magnetic therapy group it was significantly increased. Compared with the control group, the average TNF-α and IL-1β levels in the corpus callosum of the CPZ group increased significantly, but compared with the CPZ group the average levels in the magnetic therapy group had decreased significantly.Conclusions:Low frequency magnetic stimulation improves the body weight and anxiety state of mice. That is probably related to less myelin loss and inhibited inflammatory response in the corpus callosum.

Objective:To explore the efficacy and safety of intermittent infusion of ilaprazole sodium and high-dose continuous infusion of esomeprazole sodium in preventing rebleeding in patients with peptic ulcer bleeding after successful endoscopic hemostasis.Methods:This is a multi-center, interval randomized, double-blind, double-dummy, parallel controlled study. From March 3rd to June 15th, 2021, 151 patients with high risk of peptic ulcer bleeding and successfully underwent endoscopic hemostasis from 33 hospitals including the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Patients were interval randomly divided into the trial group (74 cases) and the control group (77 cases). Patients in the trial group received intermittent intravenous infusion of ilaprazole sodium once daily (20 mg administered as a 60 min intravenous infusion on day 1, and 10 mg administered as a 30 min intravenous infusion on day 2 and 3); patients in the control group received continuous intravenous infusion of esomeprazole sodium for 72 h (esomeprazole sodium 80 mg at first dose in half an hour, and 8 mg per hour continuous intravenous infusion for 71.5 h). After intravenous infusion treatment, patients of both groups were given oral ilaprazole enteric-coated tablets, 10 mg each time, once a day for 4 d. The rebleeding rate after 72 h and within 7 d after treatment and the proportion of patients who received endoscopic retreatment or surgery due to rebleeding within 72 h after treatment were analysised based on the full analysis set (72 cases in the trial group and 75 cases in the control group); and the incidence rate of adverse reactions was observed in the two groups based on the safety analysis set (74 cases in the trial group and 76 cases in the control group). Chi-square test or Fisher exact probability test was used for statistical analysis.Results:There was no rebleeding case in the trial group within 72 h and 1 case of rebleeding within 7 d (1.39%, 1/72). In the control group, there was 1 case of rebleeding (1.33%, 1/75) within 72 h and 4 cases of rebleeding (5.33%, 4/75) within 7 d. There was no significant difference in rebleeding rate either after 72 h or within 7 d after treatment between the two groups (both P>0.05). Within 72 h of treatment, no patients in both groups needed endoscopic or surgical retreatment due to rebleeding. Adverse reactions occurred in 5 cases (6.8%, 5/74) and 6 cases (7.9%, 6/76) in the trial group and control group, respectively, which recovered spontaneously without treatment. No serious adverse reactions occurred in both groups. Conclusion:In patients with high-risk peptic ulcer bleeding with successful endoscopic hemostasis, intermittent intravenous infusion of ilaprazole sodium has similar efficacy and safety as continuous high-dose intravenous infusion of esomeprazole sodium, but the dosage of intermitten regimen is less, the administration is more convenient, and it is worthy of clinical promotion.