ObjectiveTo explore the effects of Guiqi Yiyuan ointment combined with cisplatin on mice with Lewis lung cancer through the endoplasmic reticulum stress pathway and mitochondrial apoptosis pathway. MethodFifty SPF male C57BL/6 mice were randomly divided into the model group， cisplatin group （0.005 g·kg^-1）， and low， medium， and high dose groups of Guiqi Yiyuan ointment combined with cisplatin （0.005+1.6 g·kg^-1， 0.005+3.3 g·kg^-1， and 0.005+6.6 g·kg^-1）. Lewis cell suspension was inoculated under the axilla of mice in each group to construct the Lewis lung cancer xenograft mouse model. After continuous administration for 14 days， the mice were sacrificed. The body weight of the mice was measured， and the tumor weight was measured after the tumors were removed. The organ index and tumor inhibition rate were calculated. Hematoxylin-eosin （ HE） staining was used to observe the pathological changes in tumor tissue. Flow cytometry was used to detect the apoptosis rate of tumor cells and the ratio of reactive oxygen species （ROS）. Western blot was used to detect the expression of glucose-regulated protein 78 （GRP78）， phosphorylated activated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， activated transcription factor 4 （ATF4）， and apoptosis protein C/EBP homologous protein （CHOP） in the endoplasmic reticulum stress pathway， as well as cysteine aspartate protease-9 （Caspase-9）， B-cell lymphoma-2（Bcl-2）， and Bcl-2 associated X protein（Bax） in the mitochondrial apoptosis pathway. ResultCompared with those in the model group， the mice in the groups of Guiqi Yiyuan Ointment combined with cisplatin had shinier fur and better mental response status. Tumor mass was reduced in all treatment groups （P<0.05）， and tumor inhibition rate was increased in all treatment groups （P<0.05）. The thymus and spleen indices of the combined group were increased （P<0.05）， and obvious pathological changes were observed in the tumor tissue of all treatment groups， with a gradual decrease in heteromorphism. Destruction of massive tumor tissue was observed in the high-dose combined group， and the apoptosis rate and ROS generation rate of tumor cells were increased in all treatment groups （P<0.05）. The protein expression level of Bcl-2 in the tumor tissue gradually decreased （P<0.05）， while the protein expression levels of GRP78， p-PERK， ATF4， CHOP， Bax， and Caspase-9 were significantly increased （P<0.05）. Compared with the cisplatin group， tumor mass was reduced in the combined group （P<0.05）， and tumor inhibition rates in the low and high-dose combined groups were increased （P<0.05）. The thymus index， spleen index， apoptosis rate of tumor cells， and ROS ratio in the combined group were significantly increased （P<0.05）， while the protein expression levels of GRP78， p-PERK， Bax， and Caspase-9 were increased in the low and high-dose combined groups （P<0.05）. The protein expression levels of ATF4 and CHOP were increased in the combined group （P<0.05）， while the expression level of Bcl-2 protein gradually decreased （P<0.05）. ConclusionGuiqi Yiyuan ointment combined with cisplatin can exert anti-tumor effects in mice with Lewis lung cancer， reduce tumor mass， increase tumor inhibition rate， and induce apoptosis of lung cancer cells. Its mechanism may be related to the regulation of the endoplasmic reticulum stress pathway and mitochondrial apoptosis pathway.

Objective To explore the action mechanism of tauroursodeoxycholic acid(TUDCA)promoting intracellular clearance of Burkholderia pseudomallei(B.pseudomallei)in RAW264.7 macrophages.Methods After TUDCA of different concentrations were used to treat RAW264.7 cells pre-infected with B.pseudomallei for 8 h or not,flow cytometry was applied to detect the apoptosis of the infected and control cells.In addition,another endoplasmic reticulum stress(ERS)inhibitor 4-PBA was used to detect the apoptosis and proliferation of host cells after B.pseudomallei infection with Annexin-V/PI double staining and MTT cell proliferation assay.Furthermore,after transfected with CHOP siRNA,Western blotting and flow cytometry were employed to detect the effect of TUDCA on the expression levels of Caspase-3 and Caspase-12 and the changes in apoptotic rate after B.pseudomallei infection,respectively.Finally,the effect of TUDCA on intracellular multiplication of infected RAW264.7 cells were observed to estimate the CFU value in the presence and absence of CHOP siRNA.Results Under different concentrations of TUDCA,100 or 200 μmol/L TUDCA significantly reduced B.pseudomallei-induced apoptosis in RAW264.7 cells(P＜0.05).Meanwhile,both TUDCA and 4-PBA treatment could decrease the apoptosis induced by B.pseudomallei infection by ERS(P＜0.05).Further,the expression levels of Caspase-3 and Caspase-12 were obviously increased after B.pseudomallei infection compared with uninfected groups,but their expression levels in the siCHOP group was significantly lower than that in the siC group.Besides,flow cytometry also showed that TUDCA could reduce apoptosis induced by B.pseudomallei infection(P＜0.05),but no significant effect of TUDCA on apoptosis was observed under CHOP knockdown.Finally,intracellular CFU assay indicated that TUDCA treatment promoted the host cell clearance of B.pseudomallei(P＜0.05),but no such effect was observed in siCHOP group.Conclusion In B.pseudomallei infected RAW264.7 cells,TUDCA promotes the intracellular clearance of the bacteria by inhibiting ERS-induced apoptosis.

Objective To explore the targets and mechanism of Jiegengbai Powder in the treatment of lung adenocarcinoma based on network pharmacology and animal experiments.Methods The targets of effective components of Jiegengbai Powder were obtained from TCMSP,the targets of lung adenocarcinoma were screened from GeneCards,PharmGKB,DrugBank,TTD,OMIM databases,and the intersection targets were obtained.The protein-protein interaction(PPI)network and active components of Chinese materia medica-target network were constructed by using Cytoscape 3.8.0 software,and the key components and core targets were screened out.The intersection targets were analyzed by GO and KEGG enrichment analysis.PyMOL and AutoDockTools 1.5.6 software were used to verify the molecular docking between the key components and core targets.The lung cancer mice model was established.The mice were randomly divided into blank group,model group,cisplatin group,Jiegengbai Powder combined with cisplatin group,Jiegengbai Powder low-,medium-and high-dosage groups.After 14 days of intervention,the tumor inhibition rate was calculated,and the morphology of tumor tissues was observed by HE staining.The gene and protein expressions of PI3K,PTEN,Akt and mTOR in tumor tissues were detected by RT-qPCR and Western blot.Results The core targets of Jiegengbai Powder in the treatment of lung adenocarcinoma such as TP53,CASP3,BCL2L1 and AKT1 were screened by network pharmacology.The key pathways of enrichment were PI3K-Akt signaling pathway and so on.Jiegengbai Powder can inhibit the growth of tumor effectively.Compared with the model group,the mRNA expressions of PI3K,Akt and mTOR decreased in the Jiegengbai Powder medium-and high-dosage groups,and PTEN mRNA expression increased,the ratio of p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR decreased,and the expression of PTEN protein increased(P<0.05,P<0.01).Conclusion Jiegengbai Powder has the characteristics of multi-level and multi-target in the treatment of lung adenocarcinoma.It may promote tumor cell apoptosis and autophagy by regulating PI3K/Akt/mTOR signaling pathway,so as to achieve the anti-tumor effect of inhibiting tumor cell growth.

Objective:To evaluate the feasibility of using MRI-only simulation images for dose calculation of both photon and proton radiotherapy for nasopharyngeal carcinoma cases.Methods:T 1-weighted MRI images and CT images of 100 patients with nasopharyngeal carcinoma treated with radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2020 to December 2021 were retrospectively analyzed. MRI images were converted to generate pseudo-CT images by using deep learning network models. The training set, validation set and test set included 70 cases, 10 cases and 20 cases, respectively. Convolutional neural network (CNN) and cycle-consistent generative adversarial neural network (CycleGAN) were exploited. Quantitative assessment of image quality was conducted by using mean absolute error (MAE) and structural similarity (SSIM), etc. Dose assessment was performed by using 3D-gamma pass rate and dose-volume histogram (DVH). The quality of pseudo-CT images generated was statistically analyzed by Wilcoxon signed-rank test. Results:The MAE of the CNN and CycleGAN was (91.99±19.98) HU and (108.30±20.54) HU, and the SSIM was 0.97±0.01 and 0.96±0.01, respectively. In terms of dosimetry, the accuracy of pseudo-CT for photon dose calculation was higher than that of the proton plan. For CNN, the gamma pass rate (3 mm/3%) of the photon radiotherapy plan was 99.90%±0.13%. For CycleGAN, the value was 99.87%±0.34%. The gamma pass rates of proton radiotherapy plans were 98.65%±0.64% (CNN, 3 mm/3%) and 97.69%±0.86% (CycleGAN, 3 mm/3%). For DVH, the dose calculation accuracy in the photon plan of pseudo-CT was better than that of the proton plan.Conclusions:The deep learning-based model generated accurate pseudo-CT images from MR images. Most dosimetric differences were within clinically acceptable criteria for photon and proton radiotherapy, demonstrating the feasibility of an MRI-only workflow for radiotherapy of nasopharyngeal cancer. However, compared with the raw CT images, the error of the CT value in the nasal cavity of the pseudo-CT images was relatively large and special attention should be paid during clinical application.

Objective To explore the application value of static progressive stretch(SPS)combined with step-wise progressive rehabilitation nursing in perioperative rehabilitation nursing of patients with unicompartmental knee arthroplasty(UKA).Methods From January 2022 to June 2023,a total of 74 patients who were scheduled to undergo UKA in the Department of Orthopedics of a tertiary A hospital in Beijing were selected by the convenient sampling method and divided into 2 groups by the random number table method,with 37 cases in each group.The experimental group was given step-by-step rehabilitation nursing combined with SPS technology,while the control group was only given step-by-step rehabilitation nursing,and the intervention lasted for 4 weeks.The knee joint activity,knee joint function score,comfort,and rehabilitation self-efficacy of the 2 groups were observed and measured before and after the intervention.Results Finally,35 patients were included in the experimental group and 36 patients in the control group.After the intervention,the knee joint range of motion,knee joint function score,comfort,rehabilitation self-efficacy and all dimensions and their total scores in the experimental group were higher than those before the intervention and those in the control group(P＜0.05).Conclusion SPS combined with progressive rehabilitation nursing can effectively improve the knee joint function and range of motion of patients after UKA,improve the comfort of patients,improve their quality of life,and enhance their rehabilitation self-efficacy,which is helpful to achieve early recovery.

Falls among the elderly are a serious public health problem. This paper reviews the application status of machine learning in fall risk identification, fall prevention training intervention, fall behavior detection and warning, analyzes the advantages and disadvantages of machine learning in the field of fall risk management for the elderly, and aims to provide ideas for personalized and accurate fall prevention practice for the elderly in the future.

Objective:Summarizing the clinical characteristics of extraneural metastasis in childhood medulloblastoma.Methods:A total of 616 cases with medulloblastoma treated in Beijing Shijitan Hospital from April 2010 to April 2019 were analyzed retrospectively, among which 11 cases developed extraneural metastasis.The age of onset, location and time of extraneural metastasis, pathological and molecular typing, treatment and prognosis were descriptively analyzed.The differences of blood biochemical indexes between medulloblastoma cases with and without extraneural metastasis were statistically analyzed by t test. Results:As of February 2020, the median follow-up period was 16 months (ranging from 3 to 69 months). Eleven cases, including 8 males and 3 females, were diagnosed with extraneural metastasis, with the incidence being about 1.8%.The median age of medulloblastoma was 6 years (2-10 years), and the median age at presentation of extraneural metastasis was 7 years (2-12 years). Extraneural metastasis occurred from 0.5 months to 38.0 months after the operation, and the affected location includes bone (6 cases), bone marrow (3 cases), lung (3 cases), pelvis (2 cases) and abdominal cavity (1 case). In these patients, the range of lactic dehydrogenase (LDH) was (2 298.00±1 570.70) U/L and neuron-specific enolase (NSE) was (201.00±68.34) μg/L, which were significantly higher than those in patients without extraneural metastasis [(249.50±46.28) U/L and (22.80±7.12) μg/L, all P<0.05]. Partial patients were treated with chemotherapy, while the majority of them were treated with palliative treatment in the terminal stage, with the survival period mostly less than 10 months. Conclusions:Although there is a low incidence of extraneural metastasis in medulloblastoma pediatric patients, the prognosis of these patients with extraneural metastasis is poor and most of them would die within one year.The most common sites include bone, followed by bone marrow and lungs, which may be related to the spread of cerebrospinal fluid and the increased levels of LDH and NSE.

Objective:To explore the effect of neutrophil-lymphocyte ratio (NLR) at the initial visit on the survival of children with newly diagnosed medulloblastoma (MB).Methods:This was a case-control study involving 61 children with newly diagnosed MB at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University from August 2018 to January 2020 .The blood cell counts, lymphocyte subsets and immunoglobulin in the periphe-ral blood were measured to calculate NLR at the initial visit.Based on the cut-off value determined by receiver opera-ting characteristic (ROC) curve, patients were divided into high NLR group (≥ 2.07, n=21) and low NLR group (<2.07, n=40). The progression-free survival (PFS) and overall survival (OS) between 2 groups were analyzed by the Kaplan-Meier method, followed by Log- rank test.The correlation between NLR at the initial visit with clinical characteristics, lymphocyte subsets and immunoglobulin of children with newly diagnosed MB was analyzed.Differences between groups were compared by the Chi- square test, Mann- Whitney U test and independent sample t test. Results:The survival analysis showed that the relapse rate (38.1% vs.10.0%, χ2=6.879, P=0.016) and mortality rate (19.0% vs.0, χ2=8.154, P=0.011) were significantly higher in high NLR group than those of low NLR group.PFS (12 months vs.19 months, χ2=9.775, P=0.002) and OS (19 months vs.20 months, χ2=8.432, P=0.004) were significantly shorter in high NLR group than those of low NLR group.No significant differences in clinical characteristics were detected between groups (all P>0.05). Compared with low NLR group, the percentage of T lymphocyte[(67.93±6.37)% vs.(73.38±8.08)%, t=2.886, df=48.865, P=0.006], T helper cells (Th)[(30.86±5.53)% vs.(34.29±7.44)%, t=2.037, df=51.981, P=0.047], and T suppressor cells (Ts)[(27.39±5.50)% vs.(30.84±6.58)%, t=2.164, df=47.581, P=0.035] were significantly lower in high NLR group.Spearman correlation analysis showed a negative correlation between NLR and T lymphocyte count ( r=-0.303, P=0.018), and Ts lymphocyte count ( r=-0.260, P=0.043). Conclusions:Children with newly diagnosed MB expressing a high level of NLR had a poor prognosis, which may be associated with T lymphocyte and Ts lymphocyte.

ObjectiveTo analyze the typical performance of initiating and responding behaviors of turn-taking in operational games for autistic children with low language function in special education schools and to provide a reference for intervention of turn-taking behaviors in operational games. MethodsFrom November, 2021 to January, 2022, a total of 23 autistic children with low language function (language ability ≤ three years old) in Shanghai Putuo District Qixing School were selected. Their linguistic ability was evaluated. A behavioral assessment approach was used to evaluate the behavior of initiating and responding behaviors of turn-taking in three operational games. The typical errors in initiating behaviors were summarized as difficult to initiate, untimely initiation, no response and abnormal initiation. The typical errors in responding behaviors of turn-taking in operational games were summarized as difficult to respond, untimely response, no response and abnormal response. ResultsThere was no significant differences in the performance of initiating behaviors among three types of operational games (χ² = 11.106, P = 0.196), and there were significant differences in the performance of responding behaviors among operational games (χ² = 26.256, P = 0.001). The initiating behaviors were postively correlated with word comprehension (r = 0.420, P < 0.05), word naming (r = 0.510, P < 0.05), and sentence imitation (r = 0.505, P < 0.05). The responding behaviors were postively correlated with word comprehension (r = 0.546, P < 0.01), word naming (r = 0.728, P < 0.01), sentence comprehension (r = 0.668, P < 0.01) and sentence imitation (r = 0.656, P < 0.01). ConclusionAutistic children with low language function showed different typical behaviors of initiating and responding behaviors of turn-taking in operational games. It is suggested that when designing training programs for turn-taking skills, targeted interventions should be made to address the typical types of errors in response and initiation turns, and individualized intervention programs should be designed to enhance children's communicative efficacy in play game and promote their language development and social participation.

Objective:To explore CT and MRI features of the endolymphatic sac tumor (ELST).Methods:The CT and MRI morphology confirmed by surgical pathology for 19 patients with ELST were retrospectively analyzed from June 2011 to May 2019 in Eye & ENT Hospital of Fudan University. The features of CT and MRI included location, size, adjacent structures invasion, CT values, bone destruction, features of T 1WI and T 2WI, enhancement distribution characteristics, dynamic enhancement curve morphology, DWI signal characteristics. The ADC values of the lesions and ipsilateral medial pterygoid muscles were compared using a paired t test. Results:Nineteen ELST patients (one with bilateral diseases) were included. Totally 20 ears (right 9 and left 11) of 13 females and 6 males were studied. The masses with slightly high-density and obscure boundary were located around the vestibular aqueduct at the posterior edge of the petrosal bone. Bone destruction involved mastoid process of the middle ear (16 ears), jugular foramen (11 ears), semicircular canal (10 ears), facial nerve canal (7 ears) and internal auditory canal (9 ears). A large amount of residual bone could be found in the interior of nineteen masses. The CT value was (78.6±21.9) HU. The lesion showed central iso-intensity and peripheral hyperintensity on T 1WI and T 2WI in 16 ears, while no obvious hyperintensity on T 1WI in the other 4 ears. The hyperintensity on T 1WI was around the margin of the lesion in 10 ears, situated at lateral side in 5 ears and all over the lesion in 1 ear. Flow voids signals could be seen in 9 ears as well. Liquid-liquid plane was seen on T 2WI in 2 ears. The solid mass portion which showed iso-intensity on both T 1WI and T 2WI presented marked enhancement on contrast-enhanced T 1WI, while other part of the mass no enhancement. DWI of 14 ears illustrates no evidence of restricted diffusion, and the ADC value [(1.25±0.08)×10 -3 mm 2/s] was slightly higher than that of the medial pterygoid muscles ( t=4.437, P=0.001). The style of time-signal intensity curves of the dynamic contrast-enhanced MRI was rapidly ascending followed by descending curves in 2 ears. Conclusion:Imaging findings of ELST have some characteristics, including located around the vestibular aqueduct at the posterior edge of the petrosal bone, bone destruction, peripheral hyperintensity on T 1WI and no restricted diffusion, which is helpful for its diagnosis.