So far， there are still no specific treatment methods for severe hepatitis and liver failure， resulting in a mortality rate of over 70%， and they are the difficulties in the treatment of critical illness in China and globally. Liver transplantation is currently the most effective treatment method for end-stage liver disease， but only 1%‍ ‍—‍ ‍2% of patients can receive the opportunity for organ transplantation. The bioartificial liver support system utilizes external mechanical， physical， and biological devices to remove various harmful substances accumulated in the patient’s body， compensate for the metabolic functions of the liver， supplement necessary substances， improve internal environment， promote the recovery of liver function， help patients get through the critical period， and save time for liver transplantation， and therefore， it is considered one of the important methods for the treatment of end-stage liver disease. Since hepatocytes are the core element of bioartificial liver， this article summarizes the sources of liver seed cells， 3D culture methods， and corresponding bioreactor culture systems and hopes to gradually solve the core issue of large-scale in vitro preparation of hepatocytes to obtain hepatocytes with adequate quantity and quality， which urgently needs to be addressed in clinical application.

Objective:To investigate the impact of residual cholesterol (RC) on the progression of arteriosclerosis in individuals receiving physical examination.Methods:A cross-sectional study. Participants aged 18 years and above who underwent arteriosclerosis testing at the Health Management Center of Zigong Fourth People′s Hospital from January to December 2023 were selected as the subjects of the study. A total of 9 016 subjects were included in this study, of whom 6 213 were considered to have arteriosclerosis. The physical examination conclusions, basic information (age, gender, body mass index, waist circumference, blood pressure, history of hypertension, history of smoking and drinking), and biochemical indicators (lipids, fasting blood glucose, liver and kidney function) were extracted in those individuals. Based on the examination results, the subjects were categorized into arteriosclerosis and normal groups. The RC levels of the participants were calculated using a formula and then the subjects were categorized into binary and quartile RC groups. Additionally, four regression models were used to analyze the impact of RC levels on the progression of arteriosclerosis while adjusting for various confounding factors.Results:The RC level was (0.63±0.44) mmol/L in the normal group and (0.76±0.61) mmol/L in the arteriosclerosis group. Based on level of RC, the normal group was divided into two subgroups: 652 individuals with elevated RC level and 2 241 with normal RC level. In the arteriosclerosis group, there were 2 069 individuals with elevated RC level and 4 144 with normal RC level. Grouped according to quartiles of RC level, the number of individuals with RC in the Q1-Q4 interval in the normal group was 838 (28.97%), 752 (25.99%), 760 (26.27%), and 543 (18.77%), respectively, showing a gradual decreasing trend. The number of individuals with RC in the Q1-Q4 interval in the arteriosclerosis group was 1 414 (22.76%), 1 438 (23.15%), 1 589 (25.58%), and 1 771 (28.51%), respectively, showing a gradual increasing trend. The difference between the groups was statistically significant ( P<0.05). After adjusting for various factors by four regression models, it was found that elevated RC levels increased the risk of arteriosclerosis progression, with a odds ratio ( OR) of 1.381, 1.242, 1.233, and 1.214, respectively. Additionally, individuals in the Q4 RC level quartile had 1.502, 1.318, 1.311, and 1.284-times higher risk of arteriosclerosis progression when compared to those in the Q1 quartile. Conclusion:The impact of RC on the progression of arteriosclerosis tend to stabilize and remain consistent, indicating that elevated RC is an independent risk factor for the progression of arteriosclerosis.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 µg/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 µg/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

Objective:To study the morphologic features of the fusion site of proximal tibial epiphysis in normal adults and analyze its potential clinical value based on Mimics three-dimensional (3D) reconstruction.Methods:CT images of knee joint of 68 patients without obvious abnormalities of lower limbs were retrospectively analyzed in electronic database of our hospital from June 2020 to June 2021, including 41 males and 27 females. The mean age of the patients was 38.7±8.4 years (range, 25-55 years), and the mean body mass index (BMI) was 25.3±4.0 kg/m 2 (range, 18.75-41.8 kg/m 2). Mimics 3D reconstruction technique was used to reconstruct the 3D model of the proximal tibia and epiphyseal fusion site. The relationship between the surface area of epiphyseal fusion site and age and BMI was studied, and the changes of cortical thickness and density at epiphyseal fusion site were also explored. Results:The fusion site of adult epiphyseal reconstructed by Mimics 3D reconstruction is a complex wavy surface structure in 3D space. The surface area of the epiphyseal fusion site was 2,994.7±645.3 mm 2 (range, 1,704.0-4,650.0 mm 2) obtained by 3-Matic Research 12.0. The fusing area of male epiphysis was 3 269.3±533.9 mm 2 than that of female 2,577.6±578.7 mm 2, the difference was statistically significant ( t=5.06, P<0.001). However, there was no significant correlation between the epiphyseal fusion site surface area and age ( R2=0.02, P=0.268) and BMI ( R2=0.04, P=0.125). Mimics software was used to obtain the CT values of bone cortex at the epiphysis line and the distal end of the epiphysis line at 10 mm and 20 mm levels as 451.059±74.953 Hu, 1,018.412±125.732 Hu and 1,414.162±107.848 Hu, respectively. The thickness of bone cortex was 1.814±0.090 mm, 2.511±0.089 mm and 3.189±0.185 mm at 10 mm and 20 mm layers of epiphysis line and distal epiphysis line, respectively. Conclusion:In this study, Mimics 3D reconstruction technique was used to visualize the fusion site of the proximal tibial epiphysis in normal adults. The epiphyseal fusion site of adult is a undulating plate-like structure, and the cortical bone density of epiphyseal fusion site is low and thin, theoretically, it is easy to fracture under indirect violence.

The construction and operation of the hospital-wide radiation protection management information system is of great significance for improving the efficiency and quality of radiation protection management. A hospital has built a hospital-wide radiation protection management system, which consisted of four modules: radiation staff management module, protection items management module, site and equipment management module, and self-inspection module. The system adopted B/S mode, carried the lightweight J2EE framework-SpringBoot framework, and used mybatis, which was flexible and practical, as the persistence layer of the system, to store the data completely in the SQLServer database.Java language was used as the system development language, and the front and back-end separation architecture was used. Each of the four modules implemented the management responsibility departments and responsible personnel to carry out the all-round management of radiation protection, and realized the integrated, information-based and standardized management of radiation protection management in the hospital.

OBJECTIVE：To provide method reference for scientifically eva luating the rationality of the use of saxagliptin . METHODS：Based on the drug instructions ，clinical guidelines ，clinical pathways ，related references ，clinical endocrinology department and pharmaceutical experts of a hospital jointly discussed and formulated the evaluation criteria for the rationality of the use of saxagliptin. AHP method was used to assign weights to various indexes of evaluation criteria ；TOPSIS method was used to analyze the use of saxagliptin of 106 cases in the hospital during Nov. 2018-Apr. 2019 retrospectively and evaluate rational drug use. RESULTS ：A total of 6 primary indicators and 12 secondary indicators were established. The first three indicators with a relatively high index weight were indications （with a weight of 0.25），dose and adjustment of administration （with a weight of 0.21）and frequency of administration （with a weight of 0.15）. Among 106 cases，39.6％ of drug use were reasonable ，51.0％ were basically reasonable and 9.4％ were unreasonable. Evaluation results made by weighted TOPSIS were consistent with the actual situation. CONCLUSIONS ：TOPSIS method weighted by AHP is reasonable and feasible for evaluating the rationality of saxagliptin use.

Objective:To evaluate the personalized 3D printed guide template used in the osteotomy for malunion of tibial fracture.Methods:A retrospective analysis was conducted of the 30 patients who had been treated for malunion of tibial fracture at Department of Orthopaedics, The First Affiliated Hospital to Zhengzhou University from January 2010 to January 2018. Of them, 15 used a personalized 3D printed guide template in the osteotomy (3D printing group). They were 9 males and 6 females, with an age of 46.3 year±8.2 years. The fracture malunion was located in the upper and middle tibia in 11 cases, in the lower tibia in 4 cases, on the left side in 6 cases and on the right side in 9 ones. There were 8 cases of varus deformity and 7 ones of valgus deformity. Their preoperative fracture deformity angle was 24.3°±5.5°. The other 15 patients were treated with conventional surgery (conventional group). They were 10 males and 5 females, with an age of 47.1 years±6.0 years. The fracture was located in the upper and middle tibia in 12 cases, in the lower tibia in 3 cases, on the left side in 5 cases and on right side in 10 cases. There were 7 cases of varus deformity and 8 ones of valgus deformity. Their preoperative fracture deformity angle was 22.5°±5.4°. The 2 groups were compared in terms of preoperative baseline data, operation time, intraoperative blood loss and postoperative recovery of the alignment of lower limb.Results:There were no significant differences in the preoperative baseline data between the 2 groups, showing comparability ( P>0.05). The 3D printing group was followed up for an average of 12 months while the conventional group for an average of 10 months. The operation time for the 3D printing group was significantly shorter than that for the conventional group(102.2 min±13.0 min versus 137.9 min ±10.5 min), the intraoperative blood loss for the former significantly less than that for the latter (77.3 mL ± 39.7 mL versus 163.3 mL ± 35.2 mL), and the postoperative malunion angle in the former significantly smaller than that in the latter (1.9°±0.4° versus 3.2°±0.9°) (all P< 0.05). The last follow-ups revealed no implant failure or re-malunion but fine healing of the osteotomy sites and good recovery of the alignment of lower limb in the 2 groups. Conclusion:A personalized 3D printed guide template used in the osteotomy for malunion of tibial fracture is an effective aid because it can facilitate precise osteotomy, reduce operation time and intraoperative blood loss and help correct the alignment of lower limb, leading to good short-term surgical outcomes.

Objective: To investigate the value of Cytomegalovirus(CMV) DNA real-time quantitative-polymerase chain reaction(RT-PCR) in different body fluids for diagnosing CMV pneumonia in immunocompetent infants. Methods: The clinical data of immunocompetent infants with CMV pneumonia who were treated in Pediatric Intensive Care Unit of Guangdong Women and Children′s Hospital from January 1^st, 2016 to February 5^th, 2018 were retrospectively analyzed.The clinical data included CMV DNA load of bronchoalveolar lavage fluid(BALF), urine, blood and cerebrospinal fluid(CSF); blood immunoglobulin(Ig)M CMV, alanine aminotransferase (ALT), X-ray and CT test of chest, combined infection, clinical manifestation and treatment. Results: Nine hundred and twenty-six infants received bronchoalveolar lavage by bronchoscope, and 34 cases were diagnosed as immunocompetent with CMV pneumonia.The infants with CMV pneumonia: the positive percentage of urine CMV DNA, blood CMV DNA, blood IgM CMV and ALT elevation were 100.0%(34/34 cases), 61.8%(21/34 cases), 52.9%(18/34 cases) and 20.6%(7/34 cases), respectively.There was no difference in positive percentage between blood CMV DNA and blood IgM CMV (χ²=0.5, P>0.05). Both the positive percentages of blood CMV DNA and blood IgM CMV were lower than those in the urine CMV DNA, and the differences were statistically significant (χ²=16.1, 20.9, all P<0.05). The positive percentages of ALT elevation were lower than those in the positive percentage of urine CMV DNA, blood CMV DNA and blood IgM CMV, and the differences were statistically significant (χ²=44.8, 11.9, 7.7, all P<0.05). Ten patients′ CSF CMV DNA were tested, and they were all negative.The median load of CMV DNA in BALF, urine and blood was 170.0×10⁵ copies/L, 130.0×10⁵ copies/L and 6.0×10⁵ copies/L.There was no difference in median load between BALF and urine (U=561, P>0.05). BALF CMV DNA load and blood CMV DNA load had a weak positive correlation (r=0.35, P<0.05), BALF CMV DNA load and age had a negative correlation (r=-0.42, P<0.05), and urine CMV DNA load and blood CMV DNA load had a positive correlation (r=0.52, P<0.05). No matter whether blood IgM CMV was positive, BALF CMV DNA load had no differences (U=92, P>0.05). The main radiographic signs were pulmonary interstitial lesions.Thirty-four immunocompetent infants with CMV pneumonia, 18 patients (52.9%) with symptoms lasted for over 2 weeks, 20 patients (58.8%) had complicated infections.They all received inductive treatment of Ganciclovir, 55.9%(19/34 cases) patients′ urine CMV DNA turned to be negative.When patients got combined infections by bacteria or mycoplasma, antibiotics were used.All discharged patients had symptoms relieved and signs improved. Conclusions BALF RT-PCR is instant, sensitive and distinctive method to diagnose CMV pneumonia.Urine RT-PCR gets specimens conveniently and safely, its positive percentage and DNA load are present well according to BALF, and is suitable for screening and monitoring CMV infection.Blood CMV DNA load and blood IgM CMV indicate viral dissemination and immunocompetence, but it is not recommended for diagnosing CMV pneumonia solely.

Objective To explore the MRI features of cavernous hemangioma in the thoracic spinal epidural space,to improve the recognition of the disease.Methods The clinical,pathological and MRI data of 7 cases with cavernous hemangioma in the thoracic spinal epidural space confirmed by surgery and pathology were analyzed retrospectively.Results 7 cases of cavernous hemangioma in the thoracic spinal epidural space were included in our study,all cases underwent MRI contrast enhancement examination and 6 of them underwent conventional MRI examination.On T1WI,4 cases showed hypointensity,2 cases showed slightly hypointensity and 1 case showed mixed slightly hypointensity.On T2WI,5 cases showed slightly hyperintensity,1 case showed slightly hypointensity. On fat suppression sequence,5 cases showed hyperintensity,1 case showed heterogeneous hyperintensity.On diffusion-weighted imaging (DWI),7 cases showed obviously hyperintensity.On contrast-enhanced images,the lesions enhanced homogeneously in 5,enhanced heterogeneously in 2.Conclusion MRI can display the location,appearance and enhancement pattern of thoracic spinal epidural cavernous hemangioma distinctly,while definite diagnosis of which still depends on pathology.