Resolving the lineage relationship between malignant cells and vascular cells in glioblastomas

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.

Licochalcone A induces cell cycle arrest in human lung squamous carcinoma cells via the PI3K/Akt signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of licochalcone A (LCA) on the proliferation and cell cycle of human lung squamous carcinoma cells and explore its possible molecular mechanism.@*METHODS@#MTT assay was used to detect the changes in proliferation of H226 cells after treatment with different concentrations of LCA for 48 h, and the IC50 of LCA was calculated. Flow cytometry was used to analyze cell cycle changes in H226 cells treated with 10, 20, and 40 μmol/L LCA, and the expressions of cyclin D1, cyclin-dependent kinase CDK2 and CDK4, and p-PI3K, PI3K, p-Akt, and Akt in the treated cells were detected using Western blotting. The effect of intraperitoneal injection of LCA for 24 days on tumor volume and weight was assessed in a BALB/c-nu mouse model bearing lung squamous carcinoma xenografts.@*RESULTS@#MTT assay showed that LCA significantly decreased the viability of H226 cells with an IC50 of 28.3 μmol/L at 48 h. Flow cytometry suggested that LCA treatment induced obvious cell cycle arrest at the G1 phase. LCA treatment also significantly decreased the expressions of cyclin D1, CDK2, and CDK4, and inhibited the phosphorylation of PI3K and Akt in H226 cells. In the tumor-bearing mice, LCA treatment for 24 days significantly reduced the tumor volume and weight.@*CONCLUSION@#LCA is capable of inhibiting the proliferation and inducing cell cycle arrest in lung squamous carcinoma cells possibility by regulating the PI3K/Akt singling pathway.

Silenced ANP32A inhibits the growth, invasion and migration of colorectal cancer in vitro via the inactivation of AKT pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of ANP32A silencing on invasion and migration of colon cancer cells and the influence of the activity of AKT signaling pathway on this effect.@*METHODS@#Colorectal cancer HCT116 and SW480 were transfected with a small interfering RNA targeting ANP32A via a lentiviral vector. At 24, 48 and 72 h after the transfection, the changes in cell proliferation and AKT activity in the cells were detected using MTT assay and Western blotting, respectively. HCT116 and SW480 cells were treated with the AKT agonist SC79 or its inhibitor MK2206 for 24, 48, 72 and 96 h, and the changes in cell migration and invasion ability were analyzed using Transwell chamber assay and cell proliferation was assessed using MTT assay. The effects of SC79 and MK2206 on migration and invasion abilities of HCT116 and SW480 cells with or without ANP32A silencing were examined using wound healing and Transwell chamber assays, and the changes in the expression of metadherin (MTDH), a factor associated with cells invasion and migration, was detected with Western blotting.@*RESULTS@#Lentivirus-mediated ANP32A silencing significantly down-regulated the activity of AKT and inhibited the proliferation of both HCT116 and SW480 cells (P < 0.01). The application of AKT inhibitor MK2206 obviously inhibited the proliferation, invasion and migration of the colorectal cancer cells (P < 0.05), while the AKT agonist SC79 significantly promoted the invasion and migration of the cells (P < 0.01). In HCT116 and SW480 cells with ANP32A silencing, treatment with MK2206 strongly enhanced the inhibitory effects of ANP32A silencing on cell invasion and migration (P < 0.05) and the expression of MTDH, while SC79 partially reversed these inhibitory effects (P < 0.01).@*CONCLUSION@#ANP32A silencing inhibits invasion and migration of colorectal cancer cells possibly by inhibiting the activation of the AKT signaling pathway.

Research Progress in Preoperative Evaluation of Lymph Node Metastasis of Bladder Cancer / 中国医学科学院学报

Bladder cancer is a common malignant tumor of the urinary system.The prognosis of patients with positive lymph nodes is worse than that of patients with negative lymph nodes.An accurate assessment of preoperative lymph node statushelps to make treatmentdecisions,such as the extent of pelvic lymphadenectomy and the use of neoadjuvant chemotherapy.Imaging examination and pathological examination are the primary methods used to assess the lymph node status of bladder cancer patients before surgery.However,these methods have low sensitivity and may lead to inaccuate staging of patients.We reviewed the research progress and made an outlook on the application of clinical diagnosis,imaging techniques,radiomics,and genomics in the preoperative evaluation of lymph node metastasis in bladder cancer patients at different stages.

Chinese expert consensus on emergency surgery for severe trauma and infection prevention during corona virus disease 2019 epidemic (version 2023) / 中华创伤杂志

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Effect of mentalization-based family therapy on depressive symptoms and non-suicidal self-injury behavior in adolescents with major depressive disorder / 四川精神卫生

BackgroundThe major depressive disorder has high prevalence among adolescents， and non-suicidal self-injury （NSSI） behaviors frequently occur among patients， therefore， major depressive disorder in adolescents has become the researching focus. ObjectiveTo explore the effect of mentalization-based family therapy （MBFT） on depressive symptoms and NSSI behavior in adolescents with major depressive disorder， and to provide references for the rehabilitation of major depressive disorder in adolescents. MethodsA total of 90 adolescent patients with major depression disorder who met the diagnostic criteria of International Classification of Diseases， 10th edition （ICD-10） for depressive disorders and attended Wuhan Mental Health Center from January to December 2022 were selected， and were assigned into study group （n=44） and control group （n=46） using random number table method. All participants received routine intervention， based on this， study group added a 60-minute MBFT intervention once a week for 8 weeks. Before the intervention and at the end of 1st， 2nd，4th and 8th week，the two groups were assessed using Hamilton Depression Scale-24 item （HAMD-24）， General Self-Efficacy Scale （GSES）， Pittsburgh Sleep Quality Index （PSQI） and Ottawa Self-injury Inventory （OSI）. ResultsThe repeated measures analysis of variance reported a statistical main effect of time， main effect of group， and interaction effect between time and group at the baseline and the end of 1st， 2nd， 4th and 8th week of treatment in HAMD-24 score （F=69.621， 15.428， 29.623， P˂0.05）， OSI score （F=176.642， 37.682， 21.873， P˂0.05）， GSES score （F=215.236， 57.421， 27.857， P˂0.05） and PSQI score （F=268.541， 61.863， 33.867， P˂0.05）. Individual effect analysis discovered a statistical difference between study group and control group at the end of 2nd， 4th and 8th week of treatment in HAMD-24 score （t=5.567， 8.645， 6.233， P˂0.01）， OSI score （t=3.675， 11.817， 9.632， P˂0.01）， GSES score （t=23.462， 31.709， 12.750， P˂0.01） and PSQI score （t=9.664， 22.457， 9.333， P˂0.01）. ConclusionMBFT may improve depressive symptoms， NSSI behavior， sleep quality and self-efficacy in adolescents with major depressive disorder. ［Funded by 2022 Natural Science Foundation Project of Hubei Province （number， 2022CFB483）］

Treatments for prolonged disorder of consciousness in recent five years: a visualized analysis / 中国康复理论与实践

ObjectiveTo investigate the current landscape and hotspots on researches about treatment of prolonged disorder of consciousness (pDOC) in the recent five years, and forecast the trends. MethodsLiterature about treatment of pDOC was retrieved from the Web of Science Core Collection database, from January 1st, 2019, to June 7th, 2023. The data were analyzed with CiteSpace 5.8.R3 to create knowledge maps for authors, countries, institutions, keywords, references, co-cited authors and co-cited literature. ResultsA total of 411 articles were included. Aurore Thibaut was the most influential author, Belgium was the most influential country, and Harvard Medical School was the institution with the most publications. The researches focused on neuromodulation, prognostic assessment and care, and management of swallowing function. The neuromodulation techniques mainly included transcranial direct current stimulation, repetitive transcranial magnetic stimulation, deep brain stimulation and transcutaneous auricular vague nerve stimulation. In the coming years, the researches trended to explore neuromodulation and mechanisms of consciousness recovery, and the main neuromodulation techniques might be deep brain stimulation and transcutaneous auricular vague nerve stimulation. ConclusionThe researches about treatment of pDOC are increasing, mainly focusing on neuromodulation, prognostic evaluation, nursing care, and training for swallowing function. More researches would focus on neuromodulation and mechanisms for restoring consciousness.

Association of peer bullying, life satisfaction with self harm among junior high school students / 中国学校卫生

Objective@#To explore the association between adolescent peer bullying, life satisfaction and self-harm, so as to provide intervention support for the prevention of adolescent self-harm behaviors.@*Methods@#In October 2022, 5 724 junior high school students from Xuancheng, Hefei, Huaibei in Anhui Province were selected by multistage stratified random cluster sampling, and a self-administered adolescent mental health behavior questionnaire was used to conduct the survey.@*Results@#The detection rate of peer bullying among adolescents was 30.0%, and the detection rates of the five self-harm behaviors including highly lethal self-harm, less lethal self-harm with visible tissue damage, self-harm without visible tissue damage, self-harm with latency damage, and psychological self-harm were 10.2%, 25.8%, 35.5%, 20.8% and 28.2%, respectively. Logistic regression model results showed a positive association between exposure to peer bullying and the five self-harmful behaviors ( OR =2.52-3.21, P <0.01), and a negative association between life satisfaction and the five self-harmful behaviors ( OR =0.19-0.33, P <0.01). Adolescent life satisfaction had a moderating effect between exposure to peer bullying and highly lethal self-harm, less lethal self-harm with visible tissue damage, self-harm without visible tissue damage, and self-harm with latency damage ( OR=1.53, 1.42, 1.30, 1.39, P <0.05), and no moderating effect between exposure to peer bullying and psychological self-harm ( P >0.05).@*Conclusion@#Peer bullying among adolescents may increase the risk of self-harm behavior. Improvement of life satisfaction can effectively mitigate the negative effects of peer bullying on adolescent self-harm.

Effects of miRNA-30a-5p and metadherin on proliferation, invasion and migration abilities of breast cancer cells / 肿瘤研究与临床

Objective:To investigate the effects of miRNA-30a-5p (miR-30a-5p) and metadherin (MTDH) on the proliferation, invasion and migration abilities of human breast cancer cells in vitro.Methods:The expression of MTDH in cancer and paracancerous tissues of 112 breast cancer patients in the database and miR-30a-5p in cancer and paracancerous tissues of 103 breast cancer patients in the database were analyzed using data from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was used to analyze the correlation between miR-30a-5p and MTDH in 1 222 breast cancer patients in the database; the data were updated to August 2022. Breast cancer MDA-MB-231 cells were divided into negative control group (transfected with negative control sequence), miR-30a-5p overexpression group (transfected with miR-30a-5p mimics), siMTDH group [transfected with small interfering RNA against MTDH (siMTDH)], siMTDH+miR-30a-5p overexpression group (transfected with both siMTDH and miR-30a-5p mimics); cell proliferation ability was detected by methyl thiazol tetrazolium (MTT) assay, cell migration ability was detected by cell scratch assay, cell invasion ability was detected by Transwell assay. The relative expressions of miR-30a-5p, MTDH, matrix metalloproteinase (MMP)-2, MMP-9, vimentin and β-catenin mRNA in cells were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR), and the expressions of MTDH, N-cadherin (N-cad), β-catenin, Snail and MMP-9 proteins were detected by Western blotting.Results:In the TCGA database, MTDH expression level was higher and miR-30a-5p expression level was lower in breast cancer tissues compared with paracancerous tissues, and the differences were statistically significant (both P < 0.001). There was a negative correlation between MTDH and miR-30a-5p expressions in 1 222 patients with breast cancer ( r=-0.134, P < 0.001). Compared with the negative control group, the cell proliferation ability was reduced in both siMTDH group and miR-30a-5p overexpression group at 24, 48 and 72 h (all P < 0.001). The cell scratch healing rate in miR-30a-5p overexpression group and siMTDH group was lower than that in negative control group [(61.6±1.6)%, (54.7±5.9)% vs. (80.3±3.0)%] (both P < 0.05). Compared with the negative control group, The number of migrated cells in miR-30a-5p overexpression group and siMTDH group was less than that in negative control group (881±50, 725±63 vs. 1 172±66) (both P < 0.05). Compared with the negative control group, the relative expressions of MMP-2, MMP-9, vimentin and β-catenin mRNA were all down-regulated in MDA-MB-231 cells of miR-30a-5p overexpression group and siMTDH group (all P < 0.05). Compared with the negative control group, the relative expressions of N-cad, β-catenin, Snail and MMP-9 proteins were down-regulated in MDA-MB-231 cells of miR-30a-5p overexpression group and siMTDH group (all P < 0.05). There was no statistical difference in the number of migrated MDA-MB-231 cells between siMTDH+miR-30a-5p overexpression group and siMTDH group (476±5 vs. 389±46, t = 3.37, P = 0.078). There was no statistical difference in the number of migrated cells between siMTDH+miR-30a-5p overexpression group and miR-30a-5p overexpression group (476±5 vs. 477±22, t = 0.02, P = 0.983). Conclusions:The expression of miR-30a-5p is negatively correlated with the expression of MTDH in breast cancer tissues, and either overexpression of miR-30a-5p or silence of MTDH in breast cancer MDA-MB-231 cells in vitro can inhibit cell proliferation, invasion and migration, but MTDH may not be a target gene of miR-30a-5p.

Optic neuritis in Guillain-Barré syndrome: a case report and literature review / 中华神经科杂志

Objective:To summarize the clinical characteristics of patients with Guillain-Barré syndrome (GBS) complicated with optic neuritis (ON).Methods:The clinical data of a patient with GBS complicated with ON, who admitted to the Department of Neurology, the First Hospital of Shanxi Medical University in December 2021, were collected, including demographic characteristics, clinical symptoms and signs, laboratory and electrophysiological data, and results of fundus color films. The patients with GBS complicated with ON reported in the literature were also reviewed.Results:A 40-year-old female patient with GBS was diagnosed by the results of electromyography and cerebrospinal fluid tests combining with the history and signs, who was treated with intravenous immunoglobulin on the 3rd day after onset. On the 8th day, her muscle strength improved significantly. However, on the 12th day, the visual field darkened, and on the 19th day, the vision decreased significantly (oculus dexter visual acuity 0.2, oculus sinister visual acuity 0.1 +1) with bilateral papilloedema, a relative afferent pupillary defect and delayed P100 response of the visual evoked potential. Obvious abnormality was not noted in optic nerve magnetic resonance imaging. Thus ON was diagnosed and treated with pulse methylprednisolone therapy. After 8 days of treatment, the visual acuity was completely recovered and there was no abnormality in the ocular fundus. A total of 28 cases of GBS complicated with ON (including the present patient) were reported in the literature. The age of onset was mostly 20-60 years, and there was no gender preference. Mycoplasma pneumoniae was the most common premorbid pathogen and was identified in 7 of the 10 cases in which the causative agent was described. ON usually involved both sides, and 21 of 28 patients had bilateral optic nerves involved. GBS preceded ON or both occurred simultaneously in the majority of patients; GBS preceded ON in 14 of 28 patients, and both occurred simultaneously in 10 of 28 patients. All patients responded well to immunotherapy, and vision was completely recovered in 20 patients. Conclusions:GBS complicated with ON is rare. Attention should be paid to the loss of vision in patients with GBS. Relevant examinations should be completed as soon as possible and immunotherapy should be given.

Anti-neurofascin 186 antibody associated acute immune sensory polyradiculopathy: a case report and review of literature / 中华神经科杂志

Objective:To describe the clinical features of a patient of anti-neurofascin 186 (NF186) antibody associated acute immune sensory polyradiculopathy (AISP), and enhance understanding of AISP/chronic immune sensory polyradiculopathy (CISP).Methods:The clinical characteristics, diagnosis and treatment of a domestic AISP patient with NF186 antibody positive admitted to the First Hospital of Shanxi Medical University in December 2021 were summarized, and the previously reported cases of AISP/CISP were systematically reviewed.Results:The patient was a 62-year-old male with acute onset. The clinical manifestations included severe sensory ataxia, increased protein in cerebrospinal fluid, no response to stimulation of the central segment of somatosensory evoked potentials (SEP), normal sensory and motor nerve conduction, and positive serum anti-NF186 antibody (1∶32). After glucocorticoid treatment, the clinical symptoms and SEP were significantly improved. The drug was stopped for 2 months, and there was no recurrence. There were 23 cases of AISP and CISP with complete data reported in the literature (including this patient). The age of onset was (54.7±17.7) years, and the ratio of male to female was 1.88. Three patients with acute onset were classified as AISP. A total of 95.7% (22/23) of patients showed sensory ataxia without limb weakness, 95.0% (19/20) of patients showed prolonged cortical potential latency or even no response, and 95.5% (21/22) of patients showed increased cerebrospinal fluid protein in varying degrees, and nerve root thickening or abnormal enhancement was not common. All 10 patients receiving immunotherapy responded to corticosteroids or intravenous immune globulin. Only 6 AISP/CISP articles reported screening for anti-ganglioside antibodies or Ranvier′s node-paranodal region-related antibodies, and no positive NF186 antibodies were reported. All the 3 patients with AISP had some characteristics of CISP/chronic inflammatory demyelinating polyradiculoneuropathy, and there was no significant difference between AISP and CISP patients in clinical features except the mode of onset.Conclusions:NF186 antibody could cause AISP, which presents as acute onset sensory ataxia. AISP is responsive to glucocorticoid therapy. Except for the mode of onset, AISP and CISP are difficult to distinguish from clinical, electrophysiological, pathological aspects and pathogenic antibodies, so they may be two different manifestations of the same disease.

Clinical efficacy and influencing factors of 125I seeds implantation in the treatment of patients with advanced lung cancer after radiotherapy and chemotherapy / 中华核医学与分子影像杂志

Objective:To investigate the clinical efficacy and prognostic factors of 125I seeds implantation in the treatment of patients with advanced lung cancer after radiotherapy and chemotherapy. Methods:From January 2017 to December 2019, 44 patients (39 males, 5 females, age 41-84 years) with advanced lung cancer after radiotherapy and chemotherapy who received 125I seeds implantation in Hebei General Hospital were retrospectively analyzed. All patients were followed up for ≥12 months, and the clinical efficacies were observed. χ2 test was used to analyze the difference of effective rates between groups. The cut-off value of postoperative dose delivered to 90% gross tumor volume ( D90) was obtained by ROC curve analysis. Kaplan-Meier method was used to calculate the survival rate and log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis to find the influencing factors for clinical efficacy. Results:The total effective rate was 72.73%(32/44) after 6 months treatment. The cut-off value of D90 was 120 Gy with the AUC of 0.771. The short-term effective rate of D90≥120 Gy group was better than that of D90<120 Gy group (18/19 vs 56.00%(14/25); χ2=8.17, P=0.004). The 1-year survival rate was 77.27%(34/44). Univariate analysis showed that age ( χ2=3.99, P=0.046), preoperative Hb ( χ2=10.60, P=0.001), tumor maximum diameter ( χ2=11.50, P=0.001) and postoperative D90( χ2=5.81, P=0.016) could affect the survival of patients. Multivariate analysis showed that preoperative Hb (hazard ratio ( HR)=0.023, 95% CI: 0.001-0.882, P=0.043) and tumor maximum diameter ( HR=40.889, 95% CI: 1.458-1 146.586, P=0.029) were prognostic factors. Conclusions:125I seeds implantation shows a good effect in the treatment of lung cancer patients after the progress of radiotherapy and chemotherapy. The short-term effect of patients with D90≥120 Gy is better than that of patients with D90<120 Gy. Preoperative Hb and tumor maximum diameter are prognostic factors of survival after implantation.

Prevention and risk factors analysis of lower extremity deep vein thrombosis after high tibial osteotomy / 中华骨科杂志

Objective:To investigate the prevention and risk factors of deep vein thrombosis (DVT) in the lower extremity after medial open wedge high tibial osteotomy (HTO).Methods:A total of 128 patients who underwent medial open wedge HTO in the Third Hospital of Hebei Medical University from January 2020 to October 2022 were retrospectively analyzed, including 45 males and 83 females, aged 59.3±6.8 years (range, 44-87 years). Postoperative anticoagulation with enoxaparin sodium was applied at a randomized dose of 4,000 AXaIU/d or 6,000 AXaIU/d. Gender, age, history of chronic diseases (hypertension, diabetes), smoking history, body mass index, and body fat percentage were collected. On admission, the risk of DVT was assessed using the Caprini scale and calf circumference was measured. Hemoglobin, D-dimer, antithrombin III, activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), fibrinogen degradation products (FDP), glutathione, glutathione, urea, creatinine, uric acid were recorded. Patients were divided into DVT group and non-DVT group according to whether DVT occurred after operation. Binary logistic regression was used to analyze the independent risk factors of DVT after HTO. The receiver operating characteristic (ROC) curve was plotted, and the area under curve (AUC) was calculated to analyze the predictive value of the postoperative Caprini scale in the occurrence of DVT after HTO.Results:A total of 128 patients were enrolled, 83 patients were treated with enoxaparin sodium 4 000 AXaIU/d and 45 patients were treated with enoxaparin sodium 6 000 AXaIU/d. According to the results of color Doppler examination of bilateral lower extremity veins on the third day after operation, DVT occurred in 39% (50/128) of patients, including 39 cases of calf intermuscular thrombosis, 6 cases of peroneal vein thrombosis, 4 cases of posterior tibial vein thrombosis, and 1 case of popliteal vein thrombosis. DVT occurred in 36% (30/83) of patients receiving 4 000 AXaIU/d enoxaparin sodium and 44% (20/45) of patients receiving 6 000 AXaIU/d enoxaparin sodium, with no statistically significant difference (χ 2=0.84, P=0.358). Univariate analysis showed that smoking history, postoperative Caprini scale≥8, and female may be associated with the development of DVT after HTO ( P<0.05). They were included in the binary logistic regression, and the results showed that postoperative Caprini scale≥8 was an independent risk factor for DVT after HTO. The ROC curve of postoperative Caprini scale for predicting DVT after HTO was drawn, and the AUC was 0.847 (95% CI: 0.73, 0.96), the optimal cut-off value was 8, and the sensitivity and specificity were 84.2% and 77.6%, respectively. Conclusion:Caprini scale≥8 is an independent risk factor for DVT after medial open wedge HTO. Caprini scale has a good value in predicting the occurrence of DVT after HTO. The recommended dose of enoxaparin sodium is 4 000 AXaIU/d for the prevention of postoperative DVT, and increasing the dose is not associated with a decreased risk of DVT.

The PK bioanalysis method study of c-Met antibody-drug conjugate (RC108) in cynomolgus monkey / 药学学报

Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H2SO4 terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.

Determining the Clinical Characteristics, Treatment Strategies, and Prognostic Factors for Mycoplasma pneumoniae Encephalitis in Children: A Multicenter Study in China

Background@#and Purpose Most of the knowledge of Mycoplasma pneumonia (M. pneumoniae) encephalitis (MPE) in children is based on case reports or small case series. This study aimed to describe the clinical features and prognostic factors of MPE, and the efficacy of azithromycin with or without immunomodulatory therapy. @*Methods@#The medical data of 87 patients with MPE from 3 medical centers in southwestern China over a 7-year period were reviewed. @*Results@#MPE was found in children of all ages except for neonates. The most common neurological manifestations included consciousness disturbance (90%) and headache (87.4%), the most common extraneurological manifestations included fever (96.5%) and respiratory system involvement (94.3%); multisystem involvement (98.2%) and elevated C-reactive protein (CRP) (90.8%) were also prominent. M. pneumoniae was detected in cerebrospinal fluid (CSF) less often than in blood and respiratory tract secretions. Azithromycin with intravenous immunoglobulin or/and corticosteroid treatment can shorten the hospitalization duration and the clinical improvement process. Most patients (82.8%) received a favorable prognosis; serum lactate dehydrogenase (LDH) and CSF protein levels were higher in the poor-outcome group than in the good-outcome group (p<0.05). Neurological sequelae are likely to continue when the onset of this condition occurs during teenage years. @*Conclusions@#MPE generally presented with nonspecific clinical manifestations. In children with acute encephalitis accompanied by multi-system involvement and prominently elevated CRP, M. pneumoniae should be considered as a possible pathogen. Immunomodulating therapies should be recommended regardless of the duration of the prodromal period. High CSF protein

Path analysis on relationship among tested hearing thresholds, conscious hearing, and negative emotions in noise-exposed workers / 环境与职业医学

Background The correlation between noise exposure and negative emotions of noise-exposed workers has received increasing attention and related studies have been reported. However, there is a lack of research on the path and effect analysis of the relationship between noise exposure and negative emotions, which will contribute to a more comprehensive understanding of the health damage characteristics of noise in addition to hearing loss. Objective To explore the path and effects of cumulative noise exposure, tested hearing thresholds, and conscious hearing level of noise-exposed workers on negative emotions. Methods Using stratified random sampling, 312 noise-exposed workers from a machinery and equipment manufacturing enterprise were selected. Occupational history, negative emotions (including the feelings of stress, anxiety, and depression), and conscious hearing level of the workers were investigated using the Depression-Anxiety-Stress Scale (DASS-21) and a self-made questionnaire. The hearing threshold of the workers was measured by pure tone air conduction audiometry. Sound level meter was used to measure noise equivalent sound level at selected work sites. Individual cumulative noise exposure was estimated based on work site noise level and personal noise exposure history. Path analysis was used to analyze potential mediating effects of workers' hearing thresholds and conscious hearing levels on the relationship between noise exposure and negative emotions (including stress, anxiety, and depression). Results The positive rates of negative emotions among the 312 noise-exposed workers were 18.27% (57/312) for stress, 46.79% (146/312) for anxiety, and 28.53% (89/312) for depression; the cumulative noise exposure ranged from 101.0 to 136.1 dB(A)·d, with an average of 125.69 dB(A)·d. The distributions of tested hearing thresholds and conscious hearing levels among the workers exposed to noise were significantly inconsistent (P<0.001), with both unweighted and weighted Kappa values less than 0.4. The percentage of workers with conscious hearing levels higher than their hearing threshold levels was 16.0%, and the percentage of workers with conscious hearing levels lower than conscious hearing levels was 38.7%. The path analysis results showed that tested hearing thresholds had no mediating effect on the relationship between cumulative noise exposure and negative emotions. There was a partial mediating effect of conscious hearing level on the relationship between cumulative noise exposure and negative emotions, with a mediating effect value of 0.06 (95%CI: 0.03, 0.11) and a mediating effect ratio of 28.57%. Conclusion Conscious hearing plays a partial mediating role in the relationship between cumulative noise exposure and negative emotions of noise-exposed workers, while tested hearing thresholds do not.

Comparative study of corneal thickness and thinnest point position of keratoconus measured by Pentacam HR and RTVue OCT / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the difference, correlation, and consistency of corneal thickness and the thinnest point position detected by Pentacam HR corneal topography map and RTVue optical coherence tomography(OCT)in patients with keratoconus.METHODS: Cross-sectional comparative study. The corneal curvature map, corneal thickness map, thinnest point position, and thinnest point thickness were detected by Pentacam HR and RTVue OCT. Paired sample t-test was used for data consistent with normal distribution, and paired sample rank sum test was used for data inconsistent with normal distribution. Spearman correlation analysis and Bland-Altman analysis were used for the correlation and consistency of the two measurement methods.RESULTS: A total of 63 patients(105 eyes)with keratoconus were included in this study, including 49 males(77.8%)and 14 females(22.2%), aged 22.24±6.19 years; among them, relevant data of Pentacam HR topographic map: Km was 47.85±4.73D and Kmax was 55.43±8.72D. In measuring central corneal thickness and the thinnest point thickness of keratoconus, the Pentacam HR was 4.70μm and 19.46μm thicker than the mean value measured by RTVue OCT(P&#x003C;0.05). There was no significant difference between the horizontal and vertical coordinates of the thinnest points measured by the two devices(P&#x003E;0.05). The central corneal thickness and the thinnest point thickness measured by the two devices were highly correlated, the horizontal coordinate of the thinnest point was moderately correlated, and the vertical coordinate of the thinnest point was weakly correlated. Bland-Altman analysis showed that the central corneal thickness, the thinnest point thickness, the horizontal coordinate of the thinnest point, and the vertical coordinate of the thinnest point were 95.2%(100/105)and 93.3%(98/105), 95.2%(100/105), 95.2%(100/105)respectively, which were within the 95% consistency limit, while the consistency ranges were -36.00～+26.62μm, -42.27～+3.36μm, -0.80～+0.84mm, and -1.95～+1.06mm, respectively.CONCLUSION: In keratoconus, the central corneal thickness and the thinnest point thickness measured by Pentacam HR were higher than those measured by RTVue OCT. It is not recommended that the central corneal thickness and the thinnest point thickness measured by the two instruments be interchangeable in clinical use because of the wide range of consistency between the two instruments' results. The position of the thinnest corneal point measured by the two instruments is similar and consistent, so it could be considered to replace the measured values of the two instruments in clinical use.

A qualitative study on self-harm experience of adolescents with mental disorders under environmental function model / 中国实用护理杂志

Objective:To deeply understand the psychological experience of self-harm in adolescent patients with mental disorder under environmental function model, and to provide reference for the formulation of nursing intervention measures for adolescent patients with mental disorder.Methods:Descriptive phenomenology was used to conduct in-depth interviews with 14 adolescent patients with mental disorders in Wuhan Mental Health Center From February to May 2021. The interview data were analyzed by Colaizzi′s seven-step analysis method.Results:There were 4 themes and 12 sub-themes: cognitive bias of self-harming behavior; psychological and emotional complexity: self-denial and self-loathing, pain, despair, satisfaction and comfort, shame, stigma, guilt; the causes of self-harm: family factors, school factors, personality factors and psychiatric symptoms factors; insufficient self-management ability: insufficient emotional management ability, low medication compliance, low self-efficacy.Conclusions:The self-harm behavior of adolescent mental disorder patients is not optimistic, the psychological and emotional burden is heavy, and the self-management ability is insufficient, so the intervention and prevention of self-harm behavior should be further strengthened.

Analysis on mechanisms of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstones and cholecystitis based on network pharmacology / 国际中医中药杂志

Objective:To analyze the mechanism of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstone and cholecystitis based on network pharmacology; To conduct a comparative analysis.Methods:The chemical components of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid and their drug targets were collected from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). DAVID 6.8 database was used to search for the associated diseases of the drug targets. The disease targets of gallstone and cholecystitis were collected from GeneCards and other databases. The protein-protein interactions network was established based on the intersecting targets of three drugs and two diseases. KEGG enrichment analysis was performed based on the DAVID 6.8 database. Cytoscape 3.7.1 software was used to construct a complex network and topology analysis of component- target- disease between three drugs and diseases.Results:222 chemical components and 3 133 drug targets were collected for Jindan Tablets. 104 chemical components and 1 425 action targets were collected for Xiaoyan Lidan Tablets. 1 chemical component and 119 action targets were collected for ursodeoxycholic acid. The three drugs were associated with 31 diseases. 1 382 disease targets for gallstones and cholecystitis were collected. There were 237, 163 and 33 targets for gallstones and cholecystitis in the three drugs, of which 17 were shared by the three drugs and 20 were shared by Jindan Tablets and Xiaoyan Lidan Tablets. Based on the DAVID database, 113, 74 and 10 significant KEGG enrichment pathways were obtained for the three drugs respectively.Conclusions:The three drugs shared many targets and pathways in the treatment of gallstones and cholecystitis, which all had the function of regulating metabolism and inhibiting inflammatory response, while participating in apoptosis, oxidative stress and cancer pathology process. However, they had their own special effects, with Jindan Tablets favoring involving in the cancer process and inhibition of inflammation, and promoting angiogenesis. Xiaoyan Lidan Tablets and ursodeoxycholic acid focused on regulating cholesterol metabolism, and Xiaoyan Lidan Tablets also regulated steroid metabolism and inhibit inflammation, while ursodeoxycholic acid regulated bile acid metabolism.

Influence of SOX7 gene methylation on the proliferation, migration and invasion of renal cancer cells and its clinical value / 国际生物医学工程杂志

Objective:To study the clinical value of SRY-Box transcription factor 7 ( SOX7) gene methylation in renal cancer and its effect on the biological behavior of renal cancer cells. Methods:80 patients with renal cancer (the kidney cancer group) and 50 patients with benign renal disease (the control group) were selected as the research subjects. Synthetic oligonucleotide sequences (MON, UMON, and CON) were designed and transfected into A498 renal carcinoma cells. Methyl-specific PCR was used to detect the methylation status of the SOX7 gene in the tumor and adjacent tissue of the kidney cancer group as well as in the renal tissue of the control group. The relationship between SOX7 gene methylation and clinicopathological factors was analyzed. The migration and invasion of A498 renal cancer cells in the MON group, UMON group, and CON group were detected by the Transwell chamber. Results:The SOX7 gene methylation rate in tumor tissue of the kidney cancer group was significantly higher than that of the control group and the adjacent tissue, and the difference was statistically significant (χ 2 = 67.522, P < 0.05). The SOX7 gene is methylated in renal cancer cell lines such as Caki-1, 786-O, 769-P, while it is unmethylated in A498 renal cancer cells. There were no statistical differences in the SOX7 gene methylation rate in the tumor tissue of the renal cancer group in terms of gender, age, or pathological type (all P > 0.05). There were statistical differences in the degree of differentiation, maximum tumor diameter, lymph node metastasis, tumor number, and TNM staging in the renal cancer group in terms of tumor tissue SOX7 gene methylation rate (all P < 0.05). After transfection with MON, the SOX7 gene methylation of A498 renal cancer cells could be successfully induced, and the day-1 to day-7 cell viability, cell migration, and invasion numbers of A498 renal cancer cells in the MON group were significantly higher than those in the UMON group and the CON group ( P < 0.05). Conclusions:Hypermethylation of the SOX7 gene can promote the proliferation, migration, and invasion of renal cancer cells and has important clinical value in the evaluation of the disease and prognosis of renal cancer.