OBJECTIVE To optimize the stir-frying process of Platycodon grandiflorum， compare the protective effect of P. grandiflorum on lung injury in mice before and after stir-frying， and preliminarily explore the characteristics of “enhanced efficacy through processing” of stir-frying P. grandiflorum. METHODS On the basis of single-factor experiment， the stir-frying time， temperature and frequency were taken as factors， and the comprehensive scores of appearance traits， platycodin D content and alcohol extract content were taken as indexes. Box-Behnken response surface experiment was designed to optimize the stir-frying process of P. grandiflorum and verify it. The mice were divided into blank control group， model group， dexamethasone group （positive control drug， 5 mg/kg）， P. grandiflorum low-dose and high-dose groups （0.6，1.2 g/kg）， fried P. grandiflorum low and high dose groups （0.6， 1.2 g/kg）， with 8 mice in each group. The treatment was given once a day for 10 consecutive days. After the last administration， acute lung injury model was established by intratracheal instillation of lipopolysaccharide. The levels of interleukin-6 （IL-6）， IL-1β， tumor necrosis factor-α （TNF-α） in serum and superoxide dismutase （SOD）， myeloperoxidase （MPO） and malondialdehyde （MDA） in lung tissue were detected， lung wet/dry weight ratio and thymus index were calculated， and the pathological changes of lung tissue were observed. RESULTS The optimum processing conditions were as follows：stir- frying temperature of 120 ℃， stir-frying time of 12 min， stir-frying frequency of 19 r/min； the comprehensive scores of the three batches of process verification were all greater than 97 points， RSD＜3% （n＝3）. The results of pharmacodynamic experiments showed that compared with blank control group， the lung dry-wet weight ratio as well as the levels of IL-6， IL-1β， TNF-α， MPO and MDA in the model group were significantly increased （P＜0.01）， the thymus index and SOD level were significantly decreased （P＜0.01）， and the lung tissue was significantly damaged. Compared with model group， above indexes of the mice in each administration group were significantly improved （P＜0.01）， and the lung tissue injury was significantly reduced. At the same dose， except for the lung dry-wet weight ratio， the above indexes of the mice in the stir-fried P. grandiflorum groups were significantly improved compared with P. grandiflorum 涵。E-mail：495758271@qq.com groups （P＜0.05）， and the lung tissue damage was further reduced. CONCLUSIONS The optimized stir-frying process is stable and feasible. The protective effect of stir-fried P.grandiflorum on acute lung injury in mice is better than that of raw products at the same dosage.

Purpose To explore the feasibility of prenatal MRI as a supplementary imaging examination of fetal multicystic dysplastic kidney(MCDK),and to improve the accuracy of imaging diagnosis.Materials and Methods The MR images of 104 fetuses diagnosed as MCDK by prenatal fetal MRI in Hubei Maternal and Children's Hospital from January 2018 to December 2021 were retrospectively analyzed.The results of fetal MRI were compared with those of autopsy or postnatal surgery,ultrasound and MRI,and the diagnostic accuracy of MRI and ultrasound was compared,respectively,the advantages of MRI combined with ultrasound in the diagnosis of MCDK was also analyzed.Results Among 104 fetuses diagnosed as MCDK by MRI,there were 102 cases with MCDK and 2 cases with misdiagnoses.Amniotic fluid was obviously reduced or absent in 4 cases.Among the 102 cases of MCDK,58 cases(56.9％)were correctly diagnosed as MCDK by ultrasound,40 cases(39.1％)were identified with polycystic alterations,without diagnosed as MCDK,and 4 cases(3.9％)were misdiagnosed as other diseases(1 case with adult polycystic kidney,1 case with multiple renal cyst and 2 cases with renal absence).Conclusion Compared with prenatal ultrasound,prenatal MRI can obtain more information,especially in oligohydramnios and maternal obesity affecting the quality of ultrasound image.MRI can be used as a reliable supplementary method of prenatal ultrasound.

Objective:To explore the value of amide proton transfer-weighted (APTw) imaging and intravoxel incoherent motion (IVIM) imaging for diagnosing and evaluating the pathological differentiation of cervix squamous cell carcinoma (CSCC).Methods:This study was a diagnostic trial. Totally 56 patients pathologically diagnosed with CSCC at the First Hospital of Lanzhou University from October 2021 to October 2022 were retrospectively collected, as the CSCC group. And 36 female healthy volunteers who underwent physical examinations at the First Hospital of Lanzhou University from October 2021 to October 2023 were recruited as the control group. CSCC patients were divided into well-moderately differentiated ( n=34) and poorly differentiated groups ( n=22). The region of interest was placed in the lesions of CSCC group and normal cervical stroma of control group, and the quantitative parameters for asymmetric magnetization transfer ratio (MTR asym) of APTw imaging and pure diffusion coefficient (D), false diffusion coefficient (D *) and perfusion fraction (f) for IVIM were obtained. The independent sample t test was used to compare the differences in quantitative parameters between the two groups, the logistic regression model was used to establish combined parameters for the quantitative parameters with statistical significance between the two groups. The receiver operator characteristic curve was used to evaluate the diagnostic efficacy of single quantitative parameters and combined parameters to distinguish the CSCC group from the control group, and the well-moderately differentiated group from the poorly differentiated group in CSCC patients. The area under the curve (AUC) was compared using the DeLong test. Results:There were significant differences in MTR asym, D and f between CSCC group and control group ( t=-9.79, 10.09, 11.35, P<0.001). Also, significant differences were found for MTR asym and D between the well-moderately differentiated and poorly differentiated group ( t=4.11, -3.76, P<0.001). There was no significant difference in other quantitative parameters ( P>0.05). When comparing the CSCC group and control group, the AUC (95% CI) of MTR asym, D, f and combined parameter (MTR asym+D+f) were 0.887 (0.804-0.944), 0.940 (0.871-0.979), 0.968 (0.909-0.993), 0.995 (0.950-1.000). The AUC of the combined parameter was higher than those of MTR asym and D, with statistical significance ( Z=3.07, 2.06, P=0.002, 0.040). When comparing the well-moderately differentiated and poorly differentiated group, the AUC (95% CI) of MTR asym, D, and combined parameter (MTR asym+D) were 0.789 (0.660-0.887), 0.775 (0.644-0.876), 0.852 (0.731-0.932). There was no significant difference between each two AUCs ( P>0.05). Conclusion:The quantitative parameters of APTw and IVIM imaging can be used to diagnose and preliminarily evaluate the pathological differentiation of CSCC. Joint parameters can improve the diagnostic efficiency of CSCC.

OBJECTIVE To investigate the effects of different drying aids on the hygroscopic property of extract powder of modified Liujunzi decoction （MLJZD）， and screen the best drying aid. METHODS MLJZD extract was mixed with β-cyclodextrin， microcrystalline cellulose， lactose， arabic gum， maltodextrin， corn starch， mannitol， dextrin， soluble starch and pre-gelatinized starch at the mass ratio of 1∶0.3 and 1∶0.5， respectively. The extract powder was prepared after vacuum drying. Physical fingerprints were established with 8 physical indexes， including moisture content， bulk density， vibrating-solid density， gap rate， Carr index， Hausner ratio， angle of rest and hygroscopicity， and then similarity evaluation was performed. The matrix hotspot map was drawn to analyze the influence of physical indexes on hygroscopicity. The moisture absorption rate of MLJZD extract powder was measured at room temperature for 2， 4， 8， 10 h and 1， 2， 3， 7 d. The moisture absorption rate-time curve was drawn， and the best auxiliary materials were selected by comparison. RESULTS The similarity evaluation results of physical fingerprint showed that the prepared MLJZD extract powder were stable and the similarities were above 0.90. The matrix hotspot analysis showed that there was significant correlation between bulk density and vibratory density and the moisture absorption rate of the MLJZD extract powder （P＜0.05）. The moisture absorption rate-time curve analysis showed that the moisture absorption rate of MLJZD extract powder prepared with the mass ratio of 1∶0.5 was lower than prepared with the mass ratio of 1∶0.3. Under both ratios， lactose showed the best drying aid effect， followed by soluble starch and mannitol. CONCLUSIONS Lactose， as the drying aid （under the mass ratio of 1∶0.5）， can obviously improve the hygroabsorbance effect of the extract powder of MLJZD， which provides a reference for the selection of auxiliary materials for MLJZD solid preparations.

Objective:To evaluate the clinical outcomes after implant restoration in the posterior region of severe periodontitis patients and to investigate the factors of natural tooth affecting the implant from the perspective of improving natural periodontal health, which may provide a reference for clinical practice.Methods:Fifty-three patients with severe periodontitis who visited the Department of Periodontology at the Affiliated Stomatological Hospital of China Medical University from June 2014 to June 2023 and completed posterior implant treatment with single crown were included, among which were 16 males and 37 females, aged (52.2±8.0) years old, with a total of 136 implants, 135 adjacent natural teeth in the edentulous area. We retrospectively compared the changes of probing depth (PD), bleeding on probing (BOP) and tooth mobility (TM) before and after implant placement. Besides, we explored the effects of the natural periodontal status on PD, BOP and marginal bone loss (MBL) of the implant at the last follow-up examination by univariate analysis and multivariate analysis.Results:Fifty-three patients were followed up for (44.5±14.1) months in average, with longest interval of (8.3±2.7) months. The PD of adjacent natural teeth in the edentulous area improved from 4.3 (3.6, 4.6) mm before implantation to 3.6 (3.2, 4.0) mm in the last review ( P<0.01), while the proportion of BOP (+) improved from 69.6% (94/135) before implantation to 46.7% (63/135) in the last review ( P<0.01). The proportion of teeth with mobility≥Ⅱ decreased from 15.6% (21/135) to 5.9% (8/135) ( P<0.01). The percentage of natural teeth with PD≥4 mm in the same segment improved from 21.0% (13.3%, 26.0%) before implantation to 18.0% (12.0%, 25.0%) in the last review ( P<0.05). The BOP (+)% improved from 29.0% (24.0%, 35.0%) before implantation to 23.0% (18.0%, 31.0%) in the last review ( P<0.05), and the number of teeth with mobility≥Ⅱ decreased from 0.0 (0.0, 1.0) to 0.0 (0.0, 0.8) ( P<0.05). The functional tooth unit score of full natural teeth increased from 8.0 (6.0, 10.0) points before implantation to 12.0 (12.0, 12.0) points in the last review ( P<0.01). PD≥4 mm % increased from 11.0% (6.0%, 25.0%) before implantation to 13.0% (3.0%, 21.0%) in the last review ( P<0.05) and there was no significant differences in BOP (+)% [(17.0±9.7) % vs (14.6±7.2) %, P>0.05]. The number of teeth with mobility≥Ⅱ decreased from 1.0 (0.0, 1.8) to 0.0 (0.0, 0.8) ( P<0.05). Conclusions:Under the premise of regular supportive care, implant restorative treatment in the posterior region of severe periodontitis patients is helpful to improve the PD, BOP and TM of remaining natural teeth. Besides, the stages and grades of periodontitis at initial diagnosis can affect the PD and BOP of implants.

In recent years,with the development of gene testing and new drug research,the diagnosis and treatment of inherited diseases have made rapid progress,corresponding to higher requirements for genetics education.As a teacher of medical genetics,the author joined the course remodeling during last 10 years from a web-based study of genetic disorders to a"case-based learning"supported by flipped classroom in order to optimize teaching effects and learning outcomes.The result of this remodeling project proposes a new strategy to guide perspectives course de-sign in future.

Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer's disease (AD). The blood-brain barrier (BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1 (Cav-1) expression was enhanced after P. gingivalis infection. Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain (RgpA) were detected. Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a (Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.
Animals ; Rats ; Bacteremia/metabolism* ; Blood-Brain Barrier/microbiology* ; Caveolin 1/metabolism* ; Gingipain Cysteine Endopeptidases/metabolism* ; Permeability ; Porphyromonas gingivalis/pathogenicity* ; Transcytosis ; Virulence Factors/metabolism*

Objective To explore the radiation shielding optimization plan for a medical proton cyclotron developing and commissioning building at various commissioning stages. Methods According to the maximum source termsat different commissioning stages, we used the empirical formula to estimate the instantaneous dose rate at the point of interest outside the shield of the building, and optimized the building’s shielding ateach commissioning stage. Results When adding 1.0 m mobile concrete shielding blocks (“blocks” below) each to wall 3 and wall 4 at the cyclotron commissioning stage, 1.0 m blocks to wall 4 and 1.25 m blocks to wall 5 at the beam transport line commissioning stage, and 1.0 m blocks to wall 9 and 0.4 m blocks to the ceiling at the simulated treatment room commissioning stage, the dose rates at the points of interest outside the shield could meet the dose rate limit requirements. Conclusion The application of mobile concrete shielding blocks not only meets the shielding requirements, but also has economical and space-saving advantages, conforming to the principle of shielding optimization. This can be an approach to the optimization of radiation shielding for high-energy particle accelerators or similar scientific projects.

Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.