Imprinted genes play a key role in regulating mammalian placental and embryonic development. Here, we generated glutaminyl-peptide cyclotransferase-knockout (Qpct^-/-) mice utilizing the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) platform and identified Qpct as a novel anti-angiogenic factor in regulating mouse placentation. Compared with Qpct^+/+ mice, placentae and embryos (Qpct^-/+ and Qpct^-/-) showed significant overgrowth at embryonic Day 12.5 (E12.5), E15.5, and E18.5. Using single-cell transcriptome analysis of 32 309 cells from Qpct^+/+ and Qpct^-/- mouse placentae, we identified 13 cell clusters via single-nucleus RNA sequencing (snRNA-seq) (8880 Qpct^+/+ and 13 577 Qpct^-/- cells) and 20 cell clusters via single-cell RNA sequencing (scRNA-seq) (6567 Qpct^+/+ and 3285 Qpct^-/- cells). Furthermore, we observed a global up-regulation of pro-angiogenic genes in the Qpct^-/- background. Immunohistochemistry assays revealed a notable increase in the number of blood vessels in the decidual and labyrinthine layers of E15.5 Qpct^-/+ and Qpct^-/- mice. Moreover, the elevation of multiple pairs of ligand-receptor interactions was observed in decidual cells, endothelial cells, and macrophages, promoting angiogenesis and inflammatory response. Our findings indicate that loss of maternal Qpct leads to altered phenotypic characteristics of placentae and embryos and promotes angiogenesis in murine placentae.
Animals ; Female ; Pregnancy ; Mice ; Placentation/genetics* ; Single-Cell Analysis ; Gene Expression Profiling ; Mice, Knockout ; Transcriptome ; Placenta/blood supply* ; Neovascularization, Pathologic/genetics* ; Genomic Imprinting ; Single-Cell Gene Expression Analysis ; Angiogenesis

Objective:To investigate the effect and safety of rituximab, programmed death 1 (PD-1) monoclonal antibody, and Bruton tyrosine kinase (BTK) inhibitor on elderly refractory primary central nervous system lymphoma (PCNSL).Methods:The clinical data of an elderly patient with refractory PCNSL treated with the combination of rituximab, PD-1 monoclonal antibody and BTK inhibitor in the First Hospital of Jilin University in February 2020 were retrospectively analyzed. The relevant literature was reviewed.Results:The patient had primary central nervous system diffuse large B-cell lymphoma (high-risk group), and the Memorial Sloan Kettering Cancer Center (MSKCC) score was 2 (estimated overall survival time was 7 months). Disease progressed after 1 course of treatment. Complete remission was achieved after the therapy of rituximab, PD-1 monoclonal antibody combined with BTK inhibitor. PD-1 monoclonal antibody maintenance therapy was performed and patient was followed up until November 17, 2021. The patient's condition was stable. The second progression-free survival (PFS) time was 20 months, and the overall survival time was 21 months. The patient well tolerated the new drug treatment, and no adverse reactions of grade 3 or above occurred.Conclusions:The new targeted combination therapy can be used as a treatment option for elderly PCNSL patients, which can further improve the curative effect and significantly improve the prognosis.

Objective:To compare the expectation and perception of rehabilitation services for patients with work injury with or without early intervention. Methods:From August, 2017 to February, 2018, 350 inpatients with work injury accepted early intervention and non-early intervention were investigated with the modified ServQual scale. Results:There was no significant difference in the expectation between the inpatients accepted early intervention and non-early intervention (t < 1.904, P > 0.05). In both groups, expectation was the highest in assurance and responsiveness dimension, and the lowest in reliability dimension. The perception was higher in the early intervention group than in the non-early intervention group. In both groups, perception was the highest in tangibility, and the lowest in empathy. Conclusion:Early intervention of rehabilitation may improve the perception of services.

Objective To analyze the dosimetric advantages of CT-guided interstitial brachytherapy for recurrent cervical cancer. Methods A total of 16 patients with recurrent cervical cancer after radical surgery and adjuvant external beam radiotherapy received interstitial brachytherapy with CT-guided implantation of metal needles. The high-risk clinical target volume (HR-CTV) was given 36 Gy in 6 fractions.D90for HR-CTV in the brachytherapy and the cumulative D2 cm3values for the bladder,rectum,and sigmoid colon in the previous external beam radiotherapy and the brachytherapy were analyzed.Results The mean D90value for HR-CTV was 52.5±3.3 Gy. The cumulative D2 cm3values for the bladder, rectum, and sigmoid colon were 85.6±5.8 Gy,71.6±6.4 Gy,and 69.6±5.9 Gy,respectively.The mean number of metal needles was 6.1±1.5 in each brachytherapy. The actual 1-year overall survival and local control were 81% and 69%, respectively. Conclusions CT-guided interstitial brachytherapy for recurrent cervical cancer shows good dose-volume histogram parameters and few complications, so it may be clinically feasible. However,its long-term clinical efficacy needs further observation.

Objective To investigate the effects of a Chinese medicine Xiao Aiping injection on the pathological changes of liver tissues in rat models, the migration ability of cancer cells in hypoxic tumor microenvironment, and explore their mechanism of action. Methods Sixty SPF 5-week old male Sprague-Dawley rats were randomly divided into model group (n=48) and blank control group (n=12). The model group was intraperitoneally injected with diethylnitrosamine to establish hepatocellular carcinoma model, and the blank control group was injected equal amount of normal saline. After 14 weeks, the model group was equally divided into three groups, two of them received the Xiao Aiping injection at a low and high dose, respectively, and the rest of model group and the blank control group were injected with normal saline once per day for five days, lasting for consecutive four weeks. Liver specimens were collected at the nineteenth week, and the rat liver cancer and liver tissues were examined by pathology. In the hypoxic environment induced by CoCl2, the effect of Xiao Aiping injection on the migration ability of hepatocellular cancer SMMC-7721 and HepG2 cells was assessed by wound healing experiment, and the expression of IL-6 mRNA was detected by real-time PCR assay. Results Compared with the blank control group, hepatic tissue of the model group showed obvious hepatocellular carcinoma-like-changes indicating the successful establishment of hepatocellular carcinoma model. After treatment, compared with the model group, the pathological alterations of hepatic tissue of Xiao Aiping injection low and high doses groups were reduced, and were more obvious in the high dose group. Under hypoxic condition, Xiao Aiping injection obviously inhibited the migration of HepG2 cells and inhibited IL-6 expression in the liver tissues. With the same concentration, Xiao Aiping injection obviously inhibited the migration of SMMC-7721 cells, and showed an inhibiting trend of IL-6 mRNA expression, but the difference was not statistically significant. Conclutions Xiao Aiping injection can reduce the pathological changes of hepatocellular carcinoma in rat models induced by intermittent intraperitoneal injection of diethylnitresamine. In the chemically induced hypoxic environment, the effects of Xiao Aiping injection on the migration of SMMC-7721 and hepG2 cells are different. Downregulating the expression of IL-6 mRNA may be one of the mechanisms of migration inhibiting effects.

Objective To discuss the dosimetric advantage of computed tomography-guided interstitial brachytherapy compared with the conventional intracavitary brachytherapy for locally advanced cervical cancer,offering a more advantageous clinical treatment approach. Methods Twenty-eight locally advanced cervical cancer patients with bulky tumors ( tumor size>5 cm) after external beam radiotherapy received computed tomography-guided interstitial brachytherapy. Dosimetric outcomes of the current study, including the total dose ( external beam radiotherapy+ brachytherapy ) D90 for the HR-CTV and D2cc for the bladder,rectum, and sigmoid, were compared with a former patient group consisting of 30 patients who received the conventional intracavitary brachytherapy ( uterine tandem+ ovoid pairs ) . Results The mean D90 value for HR-CTV in the intracavitary brachytherapy group and interstitial brachytherapy group were (76.9±5. 7) and ( 88.1± 3. 3) Gy, respectively. The D2cc for the bladder, rectum, and sigmoid in the intracavitary brachytherapy group and interstitial brachytherapy group were (84.7±6. 8) Gy,(69.2±4. 2) Gy,(67.8±4. 5) Gy and (81.8±6. 5) Gy,(6.8±4. 0) Gy,(64.8±4. 1) Gy,respectively.1-year local tumor control rate in the intracavitary brachytherapy group and interstitial brachytherapy group were 59. 3％ and 85. 2％, respectively. Conclusions CT-guided interstitial brachytherapy shows a significant dosimetric advantage compared with the conventional intracavitary brachytherapy, and is, thereby, clinically possible feasible. However,the long term curative effect and toxicity need to be further investigated.

Objective To examine the dosimetric advantages of three-dimensional (3D) computed tomography (CT)-guided interstitial brachytherapy (BT) for target volume and surrounding normal tissue in patients with locally advanced cervical cancer,and to provide a simple and effective clinical treatment approach.Methods A total of 52 patients who had poor tumor response to external beam radiotherapy (EBRT) with a residual tumor greater than 5 cm at the time of BT were included.The patients were treated by 3D CT-guided interstitial BT using a hybrid applicator comprised of uterine tandem and free metal needles.The high-risk clinical target volume (HR-CTV),intermediate-risk clinical target volume (IR-CTV),and organs at risk (OAR) were contoured.The total dose,including external beam radiotherapy and high dose-rate BT,was biologically normalized to conventional 2 Gy fractions (EQD2).D90and D100for both HR-CTV and IR-CTV,and D2 ccfor the bladder,rectum,and sigmoid were analyzed.Results The mean D90value for HR-CTV was 88.4±3.5 Gy.The D2 ccfor the bladder,rectum,and sigmoid were 81.1±5.6,65.7±5.1,and 63.1±5.4 Gy,respectively.D2 cc≤90 Gy for the bladder and D2 cc≤70 Gy for the sigmoid were observed in all the patients.D2 cc≤70 Gy for the rectum was observed in 89% of patients.Conclusions 3DCT-guided interstitial BT has a significant dosimetric advantage for target volume accompanied by few minor complications,and thereby may be clinically feasible for treating locally advanced cervical cancer.However,its long-term efficacy and possible toxicities will require further clinical observation.

Objective To compare the clinical features of drug induced hepatitis caused by traditional Chinese medicines (TCM) and western medicines. Methods A total of 181 patients hospitalized with drug in-duced hepatitis between January and December 2015 were enrolled. Among the patients ,75 cases were in TCM group,66 cases in western medicine group and 40 cases in combined group(accepted both TCM and western medi-cine treatment). Liver biopsies were performed and Roussed Uclaf Causality Assessment Method (RUCAM) scores showed that all patients were with scores higher than 3. The data including gender,age,clinical manifesta-tions,physical signs,laboratory tests and image characteristics were analyzed individually. Results There was no significant difference in age,the pattern of liver injury,and the course of liver damage among the three groups (P>0.05). Anorexia was common symptom in all the three groups without any significant difference(P>0.05). Jaundice was most frequently observed in TCM group while fever was most commonly found in western medicine group,which both had significant difference(P< 0.05). The results of routine coagulation tests and serum albu-min values were normal in 3 group with increasing level of aminotransferase observed ,and there was no significant differences among 3 groups(P>0.05). Compared with western medicine group ,the patients in TCM group had a higher level of platelet counts ,serum levels of total bilirubin ,total bile acids(TBA)and serum iron(P<0.05), and less proportion of eosinophils and lower level alkaline phosphatase(P< 0.05). Conclusions The age,the pattern of liver injury,the course of liver damage and aminotransferase levels in patients with drug induced hepati-tis caused by TCM and western medicines were similar;however,western medicines were more likely to cause al-lergic responses and hyperbilirubinemia occurred more frequently in patients with drug induced hepatitis caused by TCM.

Objective To construct a three-dimensional (3D) dynamic head-neck finite element model which accords with the anatomical structure, and study its dynamic responses under the external force. Methods By using the neck CT images of a Chinese adult male volunteer and obtaining the 3D cervical point cloud data, the finite element model of cervical spine was established using ICEM-CFD and HyperMesh software. This model, including vertebrae, intervertebral discs, facet joints, ligaments and cartilage tissues, and combining with the established and verified head finite element model, was assembled as human head-neck finite element model with detailed anatomical structures. Results The model was validated by data of head-neck axial impact experiments reported in previously published literature. The simulation results showed that the neck deformation, head acceleration, head force and injury positions were preferably consistent with the experimental data. Conclusions The established 3D dynamic finite element model can be used to study head-neck dynamic responses and damage mechanism in the fields of traffic safety and impact injuries.