Development and validation of risk prediction model for new-onset cardiovascular diseases among breast cancer patients: Based on regional medical data of Inner Mongolia / 北京大学学报(医学版)

OBJECTIVE@#To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer.@*METHODS@#Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve.@*RESULTS@#A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration.@*CONCLUSION@#It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.

Effect of FKBP38 protein on endometrial precancerous lesions and mechanism / 中国药理学通报

Aim To build the model of the gene FKBP38(FK506 binding protein 38)conditional knock out in uterus and then investigate the effect on endometrial precancerous lesions and the underlying mechanism.Methods Transgenic mice whose FKBP38 gene was flanked with loxP were constructed by embryo microinjection. The conditional knockout of FKBP38 was obtained by breeding mice harboring two loxP sites in FKBP38(FKBP38

Digitalized analysis of the gingival and bone morphology in the maxillary anterior teeth in patient with posterior dental implant / 中华口腔医学杂志

Objective: To explore and analyze the correlation between labial gingival morphology and alveolar bone morphology of maxillary anterior teeth in patients with posterior dental implant, so as to provide reference basis for restoration design and esthetic reconstruction of anterior teeth. Methods: Sixty-four patients [24 males, 40 females (25.6±3.3) years old] who planned to receive posterior dental implant restoration were recruited randomly with the inclusion and exclusion criteria in Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University from May 2020 to May 2021. According to the visibility of periodontal probe through gingival margin, the subjects were divided into thin and thick gingival biotypes, including 29 cases of thin biotype and 35 cases of thick biotype. The 3Shape software was used to perform oral scanning, and cone beam CT (CBCT) was taken for each patient. Geomagic and Mimics software were used to measure and record the labial crown width and length, gingival papilla height, gingival angle, bone papilla height and bone margin angle of maxillary anterior teeth. Results: The crown width length ratios of maxillary central incisors, lateral incisors and canines were 0.85±0.08, 0.80±0.08 and 0.86±0.09 (F=10.71, P<0.01). The height of gingival papilla between maxillary central incisors, between central incisors and lateral incisors, between lateral incisors and canines were (3.93±0.86), (3.47±0.84) and (3.38±0.91) mm respectively (F=7.44, P<0.01), and the height of corresponding bone papilla were (3.44±0.88), (3.12±0.75) and (2.72±0.63) mm respectively (F=14.26, P<0.01). The gingival margin angles of maxillary central incisors, lateral incisors and canines were 88.3°±7.7°, 84.7°±8.9° and 81.2°±6.6° (F=13.15, P<0.01), and the bone margin angles were 103.2°±13.1°, 99.5°±11.2° and 110.6°±13.0° (F=13.25, P<0.01). The crown width length ratio (0.81±0.08), gingival margin angle (82.2°±7.4°) and bone margin angle (99.4°±12.9°) of thin gingival subjects were significantly lower than those of thick gingival subjects (0.85±0.09, 86.5°±8.6°, 108.5°±11.4°) (t=-2.79, 3.63, 5.20, P<0.01). The height of gingival papilla [(3.93±0.81) mm] and bone papilla [(3.43±0.80) mm] in thin gingival subjects were significantly lower than those in thick gingival subjects [(3.34±0.84) and (2.85±0.71) mm, respectively] (t=-4.89, -5.36, P<0.01). The height of labial gingival papilla of upper anterior teeth was positively correlated with that of bone papilla in all patients (r=0.66, P<0.01); the ratio of crown width to length of upper anterior teeth was positively correlated with the angle of bone margin (r=0.42, P<0.01); the height of anterior gingival papilla was negatively correlated with the angle of bone margin (r=-0.58, P<0.01), and the height of bone papilla was negatively correlated with the angle of bone margin (r=-0.82, P<0.01). Conclusions: The crown shape, gingival shape and alveolar bone shape of maxillary anterior teeth were different in different tooth positions. Patients with different periodontal phenotypes had different crown width length ratio, gingival papilla height, bone papilla height, gingival margin angle, and bone margin angle.

Comparison of clinical features and prognostic factors of 106 optic neuritis patients with anti-myelin oligodendrocyte glycoprotein immunoglobulin G antibody positive and anti-aquaporin 4 immunoglobulin G antibody positive / 中华神经科杂志

Objective:To compare the clinical features of patients with anti-myelin oligodendrocyte glycoprotein immunoglobulin G antibody (MOG-IgG) positive and anti-aquaporin 4 immunoglobulin G antibody (AQP4-IgG) positive optic neuritis or neuromyelitis optic spectrum disorders (NMOSD) along with optic neuritis, and to analyze prognostic factors.Methods:A total of 106 consecutive inpatients with optic neuritis as the main manifestation and with positive serum antibodies were collected in Department of Neurology, Beijing Tongren Hospital, Capital Medical University from July 2018 to August 2019. The patients were divided into MOG-IgG-positive optic neuritis (MOG-ON) group (35 cases) and AQP4-IgG-positive optic neuritis (AQP4-ON) group (71 cases) according to serum antibody type. The average follow-up period was 14.9 months (5-26 months). The clinical features and outcomes of patients with different serotypes of optic neuritis were compared, and the prognostic factors for different outcomes were analyzed.Results:Compared with AQP4-ON patients, MOG-ON patients were more common in males [37.1%(13/35) vs 15.5%(11/71), χ2=6.274], binocular involvement [48.6%(17/35) vs 19.7%(14/71), χ2=9.432], ocular pain [82.9%(29/35) vs 62.0%(44/71), χ2=4.770], papilledema [63.5%(33/52) vs 36.5%(31/85), χ2=9.442] and peripapillary hemorrhage [15.4%(8/52) vs 2.4%(2/85), χ2=6.286], and were rare in abnormality of other autoimmune indexes [11.4%(4/35) vs 52.1%(37/71), χ2=16.360] (all of them P<0.05). Similar to AQP4-ON, supratentorial and infratentorial tissues, the long segments of the cervical and thoracic cord and all parts of visual pathway were widely involved in MOG-ON, but the anterior segment of optic nerve in orbital was more frequently involved in MOG-ON than in AQP4-ON (χ2=17.506, P<0.001), while the optic nerve sheath was less involved in MOG-ON than in AQP4-ON (χ2=4.075, P=0.044). The proportion of corrected visual acuity ≥ 0.5 in MOG-ON patients (92.3%, 48/52) post three-month of disease onset was higher than that in AQP4-ON patients (50.0%, 34/68) (χ 2=24.374, P<0.001). Positive serum MOG-IgG was a favorable factor for vision acuity recovery in optic neuritis [ OR (95% CI): 11.537(2.090-63.690)], while older onset age [ OR (95% CI): 0.945 (0.908-0.983)], involvement with other nervous system [ OR(95% CI): 0.116 (0.031-0.439)], and involvement of optic nerve sheath [ OR(95% CI): 0.246 (0.066-0.916)] were adverse factors. The recurrence rate of MOG-ON (37.1%, 13/35) was lower than that of AQP4-ON (59.2%, 42/71; χ 2=4.550, P=0.033). The presence of other nervous system involvement was the promoting factor of optic neuritis recurrence [ OR (95% CI): 6.908 (2.312-20.634)]. Conclusions:Compared with AQP4-ON, MOG-ON patients are more common in men, presenting with binocular painful vision loss, optic disc edema and peri-disc hemorrhage, and involvement of the anterior orbital segment of the optic nerve, while involvement of the optic nerve sheath and other autoimmune index abnormalities are relatively rare. MOG-ON patients have better vision recovery and fewer recurrence after treatment than AQP4-ON. Older age of onset, participation of other nervous system, and immersion of optic nerve sheath, are adverse factors for recovery of optic neuritis, and involvement of other nervous system is also a promoting factor for recurrence of optic neuritis.

Clinical analysis of hypertrophic cranial pachymeningitis associated with anti- myeloperoxidase and anti-neutrophil cytoplasmic antibody with optic nerve dysfunction / 中华神经科杂志

Objective:To investigate the clinical characteristics, diagnosis, treatment and prognosis of patients with hypertrophic cranial pachymeningitis （HCP） associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) with optic nerve dysfunction.Methods:Clinical data of patients with MPO-ANCA associated HCP admitted to Beijing Tongren Hospital, Capital Medical University from 2008 to 2019 were collected and analyzed.Results:A total of 55 HCP patients were diagnosed, including five patients with MPO-ANCA associated HCP, two males and three females, with the onset ages ranging from 61 to 80 years.The main clinical manifestations were successively five cases of multiple cranial neuropathies, four cases of headache, four cases of chronic sinusitis, three cases of otitis media or mastoiditis，one case of cerebral infarction, while two cases of mild kidney involvement, all without lower airways involvement. Peripheral blood MPO-ANCA concentration and erythrocyte sedimentation rate were elevated in all patients, and protease 3-ANCA was negative. Cerebrospinal fluid protein content was elevated in three patients and leukocyte was increased in one patient. The abnormal frequency of gadolinium-enhanced MRI of brain scan was dura mater (five cases), optic nerve sheath (five cases), sinus mucosa (four cases), inner auditory tract meninges (three cases), orbital wall periosteum (two cases), and brain parenchyma (one case). All patients received glucocorticoid therapy, meanwhile two patients received cyclophosphamide treatment. Multiple cranial neuropathies and headache were improved，but the improvement of visual function damage was not obvious.Conclusions:MPO-ANCA associated HCP is a special type of HCP. Among the dural region involved, the optic nerve sheath is a common site of this disease, and the sinus mucosa and inner auditory canal meninges are also frequently involved. MPO-ANCA associated HCP should be distinguished, if patients with dural lesions, especially those accompanied by optic nerve sheath lesions, sinusitis, and middle ear mastoiditis.

Mechanism of Paris Forrestii (Takht.) H. Li-Suppressing the Proliferation of Acute Myeloid Leukemia Cell Lines / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of Paris forrestii (Takht.) H. Li (PCT3)-suppressing the proliferation of HL-60, K562, KG-1 and HT-93 cells.@*METHODS@#cute myeloid leukemia cell lines such as HL-60, K562, KG-1 and HT-93 were treated with Paris forrestii (Takht.) H. Li (PCT3) for 24, 48, and 72 h, and MTT assay was employed to determine the cells proliferation. Meanwhile, the apoptosis of K562, HL-60, KG-1 and HT-93 cells were detected by flow cytometry after PCT3 (Control, 4 μg/ml, 8 μg/ml) treated for 24 h and the Western blot was performed to detect the expression of PARP,Caspase-3, MCL-1, BAX, BCL-2, P53, and P27. GAPDH was used as an internal loading control.@*RESULTS@#MTT assay showed that Paris forrestii (Takht.) H. Li (PCT3) significantly inhibited the proliferation of HL-60, K562, KG-1 and HT-93 cells in concentration and time-dependent manners. Compared with the control group, the leukemia cell viabilities were significantly suppressed (r =0.9436; r =0.8623; r =0.9922; r =0.8918). Paris forrestii (Takht.) H. Li (PCT3) induced apoptosis of leukemia cells in a concentration dependent manner, compared with the control group (P＜0.05 or P＜0.01). Western blot revealed that PARP, a major enzyme in DNA damage repair, and Caspase-3 another one of the major executive apoptotic enzymes were cleaved in cell lines examined, and this cleavage was concentration dependent. Anti-apoptotic proteins such as MCL-1 and BCL-2 were down regulated by Paris forrestii (Takht.) H. Li (PCT3), and Pro-apoptotic protein BAX was upregulated. And the protein of tumor suppressor gene P53 and its downstream signaling protein P27 increased.@*CONCLUSION@#Paris forrestii (Takht.) H. Li (PCT3) can inhibit the proliferation of leukemia cells by activating endogenous apoptosis pathway, and provide a potential new drug selection for clinical treatment of AML leukemia.

Analysis of Correlation of WAS Gene Mutations with Clinical Phenotype / 中国实验血液学杂志

OBJECTIVE@#To investigate the gene mutation of patients with WAS gene defect and its correlation with clinical manifestations.@*METHODS@#Thirty-one patients consulted in Children's Hospital of Soochow University from January 2013 to February 2018 were enrolled in this study. The hot pot mutations of WAS gene in 31 patients were detected and related clinical phenotypes were analyzed retrospectively.@*RESULTS@#All patients were male. The median onset age was 1 month (range, 0-83 months). Nine mutants were reported as novel mutations among 25 mutants detected in 31 patients, including c.1234_1235dupCC, c.1093-1097delG, c.28-30dupC, c.436G>T, c.273 + 10_273 + 11dupCC, c.995_996insG, c.1010T>A, c.332_333delCC and c.683C>T mutations. There were 25 cases of classic WAS which mutations included missense mutation, deletion mutation, insertion mutation, splicing mutation and nonsense mutation, 2 cases of X-linked thrombocytopenia (XLT) were induced by missense mutation, 1 case of intermittent X-linked thrombocytopenia (IXLT) was induced by splicing mutation, 2 cases of X-linked pancytopenia were induced by missense mutation. Intravenous immunoglobulin (IVIG) and glucocorticoid therapy in IXLT patient was effective, and remission could be sustained, platelets could be increased in the short-term in treated XLT patients, but only a small part of classic WAS patients(8.0%) showed transient response to it, the IVIG and glucocorticoid therapy did not improve the status of platelet in XLP patients. Immune laboratory examination showed that CD3 was decreased in 60.0% patients, CD19 was decreased in 12.0% patients, and CD56CD16 in 4 patients was decreased, accounting for 16.0%. Out of 24 patients, 22 patients were alive after treated with hematopoietic stem cell transplantation (HSCT), 4 patients who were not given HSCT died of brain bleeding and severe infection, 1 patient diagnosed as IXLT got remission and survived.@*CONCLUSION@#WAS gene defect is an important basis for the diagnosis of WAS and related diseases. IVIG plus glucocorticoid therapy is less effective for fewer patients, the HSCT is an effective treatment for WAS.

Anesthesia management of cervical chordoma resection: A case report / 北京大学学报(医学版)

Chordoma is a slow-growing, locally invasive, lowgrade malignant tumor with a prevalence of one in 100 000, accounting for 1%-4% of all malignant bone tumors. At present, it is considered that chordoma originates from ectopic embryonic chordal tissue and can occur in any part of the spine from the skull base to the sacrum. About 50% of chordoma occurs in the sacrococcygeal region, about 30% in the skull base, and the rest occurs in the active spinal region. Cervical chordoma is rare, but it may be accompanied by difficult airways. The tumors compress the pharynx and throat forward, which can cause upper airway obstruction. If the anesthesia is not properly handled, the patient may die of asphyxia. The core issues of airway management during the perioperative period of cervical chordoma surgery involve three main parts: preoperative airway evaluation, airway management and extubation management. Difficult airway assessment often relies on physical examination indicators, such as inter-incisor gap, thyromental distance, neck circumference, Mallampati test, etc. But the accuracy is insufficient. The application of imaging examination in the observation of different tissues can make up for the inaccurate evaluation of the internal structure of the airway. Because chordoma destroys cervical vertebral body and accessories, cervical stability is impaired. Excessive cervical vertebral extention should be avoided during tracheal intubation to prevent severe compression of the spinal cord. It is better to fix the head by an assistant and perform neutral tracheal intubation. Considering that the patient with a difficult airway that could be predicted before operation, the strategy of tracheal intubation under conscious sedation with topical anesthesia was selected. After sedation and topical anesthesia, the patient was successfully intubated with optical stylet. After operation, the patient returned to ICU with tracheal catheter. On the 4th day after operation, the tracheal tube was pulled out. On the 5th day after operation, the patient was transferred to the orthopaedic ward and discharged on the 7th day after operation. It is of great significance to establish specific strategies for such operations to reduce related complications, speed up post-operative rehabilitation and save medical resources. We reported the anesthetic management of cervical chordoma cured in Peking University Third Hospital.

Effect and related mechanism on inflammatory response,proliferation and apoptosis of oxLDL-induced vascular smooth muscle cell of matrine / 中国免疫学杂志

Objective:To explore the effect and related mechanism on inflammatory response,proliferation and apoptosis of oxLDL-induced vascular smooth muscle cell of matrine.Methods:Theatherosclerotic model was conducted through treating human aort-icvascular smooth muscle cell with oxidized low density lipoprotein(oxLDL).Cell viability and proliferation was detected by CCK-8 as-say.The mRNA level of interleukin 1 beta(IL-1β),tumor necrosis factor alpha(TNF-α),IL-10 and IL-13 was tested by quantitative real-time reverse transcription PCR(qRT-PCR).Cell apoptosis was measured by flow cytometry.The expression of proliferation marker proteins antigen identified by monoclonal antibody(Ki-67) and proliferating cell nuclear antigen(PCNA),apoptosis marker proteins B cell lymphoma 2(Bcl-2) and Bcl-2-associated X protein(Bax),signal transducer and activator of transcription 3(STAT3) and signal transducer and activator of transcription 5(STAT5) was detected by Western blot.Results: Compared with control group,the mRNA level of IL-1β and TNF-α in model group was largely increased with decreased mRNA level of IL-10 and IL-13(P<0.01).Compared with model group,the mRNA level of IL-1β and TNF-α in treatment group was attenuated with enhancive mRNA level of IL-10 and IL-13(P<0.05).Cell proliferation and apoptosis in model group was higher than control group.Cell proliferation and apoptosis in treatment group was lower than model group(P<0.05).Compared with control group,the expression of Ki-67,PCNA and Bax in model group was augmented with decreased expression of Bcl-2(P<0.01).Compared with model group,the expression of Ki-67,PCNA and Bax in treatment group declined with elevated expression of Bcl-2(P<0.05).The expression of p-STAT3 and p-STAT5 in model group was higher than control group(P<0.01).The expression of p-STAT3 and p-STAT5 in treatment group was lower than model group(P<0.05).Compared with model group,the expression of Ki-67,PCNA and Bax in treatment group and model+Ruxolitinib group was decreased with enhancive expression of Bcl-2(P<0.05).The expression of Ki-67,PCNA and Bax in model+matrine+Ruxolitinib group was observably lower than model group and the expression of Bcl-2 in model+matrine+Ruxolitinib group was observably higher than model group(P<0.01).Compared with model group,the mRNA level of IL-1β and TNF-α in treatment group,model+Ruxolitinib group and model+matrine+Ruxolitinib group was attenuated with enhancive mRNA level of IL-10 and IL-13(P<0.05).Conclusion:Matrine represses inflammation,proliferation and apoptosis of vascular smooth muscle cell by inhibiting activation of JAK/STAT3 signal pathway in atherosclerosis.

Protective Effect of Norcantharidin on Collagen-Induced Arthritis Rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of norcantharidin (NCTD) on collagen-induced arthritis (CIA) rats.</p><p><b>METHODS</b>Sixty Sprague-Dawley(SD) rats were randomly divided into 6 groups (n=10): normal group, CIA model group(model group), NCTD low-dose group [1.35 mg/(kg•d)], NCTD middle-dose group [2.7 mg/(kg•d)], NCTD high-dose group [5.4 mg/(kg•d)] and methotrexate (MTX) group [1.8 mg/(kg/w)]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin (H&E) staining. The serum levels of interleukin (IL) 1β, IL-6, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), IL-17 and transform growth factor (TGF) β were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression of retinoid-related orphan nuclear receptorγt (RORγt) and forkhead box P3 (Foxp3) in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction.</p><p><b>RESULTS</b>MTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats' ankle joints compared with the model group (P<0.05 or P<0.01). All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats (P<0.05). Only middle- and high-dose of NCTD prominently decreased serum IL-1β and TGF-β levels of CIA rats (P<0.05). However, NCTD has no effect on vascular endothelial growth factor (VEGF) level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group (P<0.05). The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group (P<0.05).</p><p><b>CONCLUSIONS</b>NCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.</p>

NIPBL gene mutations in two children with Cornelia de Lange syndrome / 中国当代儿科杂志

Both children (one boy and one girl) experienced disease onset in infancy and visited the hospital due to growth retardation. They had unusual facies including thick hair, arched and confluent eyebrows, long and curly eyelashes, short nose, and micrognathia. Patient 1 had congenital heart disease (atrial septal defect and pulmonary stenosis) and special dermatoglyph (a single palmar crease). Patient 2 had cleft palate and moderate-to-severe deafness. Clinical features suggested Cornelia de Lange syndrome in both children. High-throughput sequencing was used to detect the seven known pathogenic genes of Cornelia de Lange syndrome, i.e., the NIPBL, SMC1A, SMC3, HDAC8, RAD21, EP300, and ANKRD11 genes. Sanger sequencing was used to analyze and verify gene mutations. Both patients were found to have novel mutations in the NIPBL gene. One patient had a frameshift mutation in exon 45, c.7834dupA, which caused early termination of translation and produced truncated protein p.R2612fsX20. The other patient had a nonsense mutation, c.505C>T, which caused a premature stop codon and produced truncated protein Q169X. Such mutations were not found in their parents or 50 unrelated healthy individuals.

Value of Adjuvant Radiotherapy for Thymoma with Myasthenia Gravis after Extended Thymectomy / 中华医学杂志(英文版)

<p><b>Background</b>The co-existence of myasthenia gravis (MG) and thymoma makes the surgical treatment more complicated and adjuvant radiation more controversial. The aim of this study was to investigate adjuvant radiotherapy for thymoma with MG after extended thymectomy.</p><p><b>Methods</b>A total of 181 patients with both MG and thymoma were recruited between 2003 and 2014 at Tongren Hospital, China. Among all the patients, 157 patients received radiation therapy after surgery (Group A); whereas the other 24 patients did not receive radiation therapy (Group B). According to the time that patients started mediastinal radiation therapy, we subdivided the 157 patients in Group A into subgroups (1-month subgroup, n = 98; 2-month subgroup, n = 7; and 3-month subgroup, n = 52). We then compared the effect of the mediastinal radiation therapy across these different groups using the survival rate, the rate of postoperative myasthenic crisis, and the complete stable remission (CSR) rate as the primary endpoints.</p><p><b>Results</b>There was a significant difference in the occurrence of postoperative myasthenic crisis between 1-month subgroup and Group B (χ = 4.631, P = 0.031). The rates of reaching CSR were 32.6% in 1-month subgroup, 25% in 3-month subgroup, and 22.7% in Group B, respectively. The overall survival rates of 1-month subgroup, 3-month subgroup, and Group B were 88.8%, 83.3%, and 77.3%, respectively. Analysis on the Kaplan-Meier survival curves demonstrated that within 8 years after surgery, there was no significant difference in aspects of overall survival and disease-free survival between 1-month subgroup and Group B, and between 3-month subgroup and Group B; over 8 years after surgery, the disease-free survival rates in 1-month subgroup, 3-month subgroup and Group B were 79.4%, 70.6%, and 55.3%, respectively.</p><p><b>Conclusions</b>Adjuvant radiation within 1 month after extended thymectomy may be helpful in controlling postoperative MG, such as decreasing the possibility of postoperative myasthenic crisis, and raising cumulative probabilities of reaching CSR.</p>

Saponins from Paris forrestii(Takht.)H.Li displays potent activity against acute myeloid leukemia by suppressing RNF6/AKT/mTOR signaling pathway / 中国药理学与毒理学杂志

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accu-mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi-esis and ultimately resulting in bone marrow failure. Chemotherapy is the mainstay treatment for all AML patients,however,drug resistance and clinical relapse limits its efficacy.The 5-year survival rate of AML patients is only 26.6%.Survival rates are even lower among patients ages 65 to 74 years (5.3%)and 75 years or older(1.6%).Therefore,exploring novel therapeutic agents is urgent for improving the outcome of patients with AML. Saponins are amphipathic glycosides found in traditional Chinese medicines. In the present study, we isolated a panel of saponins from Paris forrestii (Takht.) H. Li, a unique plant found in Tibet and Yunnan provinces, China. By examining their activities in suppressing acute myeloid leukemia cell proliferation, total saponins from Paris forrestii (TSPf) displayed more potent activity than individual ones.TSPf induced more than 40% AML cell apoptosis within 24 h and decreased the viability of all leukemia cell lines. TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation.TSPf downregulated pro-survival proteins Mcl-1,Bcl-xL and Bcl-2,but upreg-ulated the expression of tumor suppressor proteins p53,p27,Bax and Beclin 1.The AKT/mTOR signaling pathway is frequently over activated in various AML cells,and TSPf was found to suppress the activa-tion of both AKT and mTOR,but had no effects on their total protein expression.This was further con-firmed by the inactivation of 4EBP-1 and p70S6K,two typical downstream signal molecules in the AKT/mTOR pathway. More specifically, TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6, a recently identified oncogene in AML. RNF6 activated AKT/mTOR, and consistently, knockdown of RNF6 led to inactivation of the AKT/mTOR pathway. Furthermore, TSPf suppressed the growth of AML xenografts in nude mice models. Oral administration of 100 mg·kg-1 body weight almost fully suppressed tumor growth within 14 d, without gross toxicity. This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway. Given its low toxicity,TSPf could be developed for the treatment of AML.

Influences of scutellarin on ATP-induced inflammasome activation and pyroptosis in J774A.1 macrophages / 中国药理学通报

Aim To explore the influences of scutellarin on ATP-induced NLRP3 inflammasome activation and pyroptosis,using LPS-primed murine macrophages J774A.1 as an inflammatory cell model,and to explore the underlying mechanism.Methods The effects of scutellarin on ATP-induced pyroptosis in murine J774A.1 macrophages were analyzed by propidium iodide (PI) staining assay.The levels of IL-1β,caspase-1 and HMGB1 in cell lysates and culture supernatants were analysed using Western blot.The levels of IL-1β in cell culture supernatants were measured by cytometric beads array (CBA).Results ATP significantly induced caspase-1 activation and mature IL-1β and HMGB1 release into the culture supernatants in LPS-primed murine J774A.1 macrophages,and induced pyroptosis.Scutellarin treatment dose-dependently inhibited ATP-induced caspase-1 activation,mature IL-1β and HMGB1 release,and pyroptosis.Notably,scutellarin's inhibitory effects on ATP-induced pyroptosis were markedly reversed by the adenylate cyclase inhibitor MDL12330A and selective protein kinase A (PKA) inhibitor H89.Conclusion Scutellarin inhibits NLRP3 inflammasome activation and pyroptosis by modulating the PKA activity in macrophages,thereby exhibiting anti-inflammatory activities.

Clinical analysis of seven cases of intracranial hypertension with essential thrombocythemia / 中华神经科杂志

Objective To report the presentation,clinical course and prognosis of intracranial hypertension (IH) with essential thrombocythemia (ET).Methods Retrospective data analysis was conducted.Seven cases of IH with ET were reviewed between January 2010 and December 2016.The clinical features,and the relationship between IH and ET were analyzed.Results IH complicated with ET was more common among young and middle-aged women.Sub acute or chronic course was more common.IH was easily misdiagnosed as optic neuritis in the early stage.The median platelet count of seven patients was 559 × 109/L.Paroxysmal black haze (four cases) was the most common of the first symptom.The head MRI showed empty sella in six cases.CT venography/DSA showed venous sinus thrombosis in three cases.All the patients were given intracranial pressure lowering and other symptomatic treatment.Five cases were treated with anti ET.Results showed remission in six cases and death in one case.Conclusions In the early stage IH was often misdiagnosed.Female was more common than male in IH with ET.Dural sinus blockage was common.In addition to symptomatic treatment such as lowering intracranial pressure,the patients should also be treated with anti ET.

Grade classification of Scutellariae Radix slices based on determination of section color and lustre / 中国中药杂志

By determination the section color and lustre indexes as well as the content of baicalin in 30 batches of Scutellariae Radix slices, calculate the correlation of these two, screen the color and lustre indexes which could represent their intrinsic quality, and establish a new grade classification method based on the results. The results showed that samples met the conditions of △L≥－37, △b≥45 simultaneously were picked grade and the content of baicalin was of ≥200 mg•g⁻¹ definitely; Samples inconsistent with any one of above conditions were general grade. This research indicated that indexes of △L and △b could characterize both the color and luster of slice and intrinsic quality, so that could be used as the indexes to classify the grades of Scutellariae Radix slices accurately, easily and objectively. The research results would provide new ideas and references for grade classification of traditional Chinese medicine slices.

Preventive effect of Dark Plum Sprayagainstradiation-induced damageto the submandibular gland in rats / 医学研究生学报

Objective At present, modern medicine cannot yet clarifythe mechanism of radiation-induceddamage (RID) to salivary glands and its treatment and protective measures remain in the exploration stage .This study was to explore the mechanism of RIDto the submandibular gland and observe the effect of Dark Plum Spray ( DPS) on the submandibular gland after RID in order to provide some evidence for its further application . Methods Using the random number table , 84 healthy Wistar male rats were divid-ed into a normal, an RID model, and an experimental group ,all fed normally.The rats of the RID model groupwere left untreated , while those of the experimental group were intervened with DPS , tid, after RID.On the 1st, 7th, 14th, and 28th day after irradiation, 7 rats were taken from each group for measurement of the body weight, collection of the saliva , and calculation of the salivary flow rate.The submandibular glands were harvested for determination of the mRNA and protein expressions of autophagy-related Atg5 by RT-PCR and Western blot . Results In the 7th day after irradiation , the average body weight in NG[(239.87±16.50)g] was significantly higher (P<0.05) than UG[(213.84±14.42)g] and EG[(222.71±11.14)g].In the 14th ,28th day after irradiation, the average body weight in UG and EG were significantly lower ( P<0.05) than NG;the average body weight in EG was significantly higher ( P<0.05) than UG.In the 1st , 14th day after irradiation , the salivary flow rate in UG and EG were lower than NG but there were no significantly difference(P>0.05).In the 7th day after irradiation, the salivary flow rate in NG[(49.29±16.90)μL/min] and EG[(50.99±6.79)μL/min] were significantly higher (P<0.05) than UG[(30.13±13.19)μL/min].In the 28th day after irradiation, the salivary flow rate in NG[(69.29±11.32)μL/min] were significantly higher (P<0.05) than UG[(49.26±14.13)μL/min] and EG[(46.56±13.60)μL/min] .In the 1st , 7th and 14th day after irradiation , RT-PCR showed that the expressions of Atg 5 in UG and EG were significantly higher(P<0.05) than NG.In the 1st , 7th and 14th day after irradiation, Western blot showed that the expressions of Atg 5 in UG and EG is on the upper trend than NG;In the 1st , 7th day after irradiation , there were no significantly difference between UG and EG .In the 28th day after irradiation , Western blot showed that the expressions of Atg 5 in UG is on the declining trend than NG . Conclusion The autophagic activity of submandibular gland cells may associated with early radiation -induced injury , and Dark Plum Spray may en-hance the action of theanti-apoptosis cytokine in repairingradiation-induceddamageto the submandibular gland .

Modeling and biological effects of radiation-induced xerostomia / 中国组织工程研究

BACKGROUND: There is little information available in the mechanism of radiation-induced salivary gland injury, and its treatment and prevention are still at the exploratory stage.OBJECTIVE: To establish a rat model of radiation-induced xerostomia with 18 Gy electron beam and to observe the pathological changes of the submandibular gland and changes in saliva ingredients.METHODS: Totally 115 Wistar rats were randomly divided into exposure and control groups: the rats in the exposure group were subjected to anesthesia, and the submandibular gland received 18 Gy electron beam radiation to establish the model of radiation-induced xerostomia. The rats in the control group were only anesthetized but not exposed to radiation. The water intake was recorded at 21 dys after modeling. The saliva was collected and the submandibular gland was removed at 1, 3, 7, 14, 21, 28, 35 and 42 days to detect the saliva volume and submandibular gland index,and the morphological changes of the submandibular gland were observed by hematoxylin-eosin staining.RESULTS AND CONCLUSION: At 1-21 days after modeling, the average daily water intake was (6.42±1.91) mL in the exposure group and (4.82±1.20) mL in the control group, respectively (P < 0.05). During 42 days after modeling, the saliva secretion volume in the exposure group was lower than that in the control group, which was the lowest on day 7,and the difference was significant at 7, 21, 28 and 42 days after modeling between two groups (P < 0.05). The submandibular gland index in the exposure group was significantly lower than that in the control group at 1 and 21-42 days after modeling (P < 0.05). Hematoxylin-eosin staining results showed that in the exposure group, the rat submandibular gland appeared with inflammatory infiltration, glandular atrophy and karyopyknosis that were aggravated with time until day 42. To conclude, the rat model of radiation-induced xerostomia is established successfully with 18 Gy beam, characterized as increased water intake, decreased saliva volume and progressive aggravation of pathological injury of the submandibular gland.

Arsenic speciation in rat plasma after oral administration of realgar and Niu Huang Jie Du Pian / 药学学报

The arsenic species in rat plasma were studied after oral administration of realgar and Niu Huang Jie Du Pian (NHJDP) and the possible compatible effects of realgar was evaluated by comparing the pharmacokinetics of arsenic species after administration of realgar and NHJDP. The separation of the arsenicals was performed by a high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) technique. Dimethylarsinic acid (DMA) was found to be the main species in rats' plasma after dosing. No traces of arsenite[As(Ⅲ)], monomethylarsonic acid (MMA) or arsenate[As(V)] were detected at any sampling time points. Compared with realgar administration alone, dose-normalized peak concentration (Cmax) and AUC0-t of DMA were significantly decreased by NHJDP administration, while the tmax was significantly delayed with the clearance and apparent volume of distribution significantly increased, indicating that the pharmacokinetics of As from realgar was affected by other ingredients in the compound prescription of NHJDP.

Sequence and timing of immunosuppressants-thymectomy combination therapy in patients with myasthenia gravis / 中华胸心血管外科杂志

Objective Following the prognosis of patients with myasthenia gravis(MG) who received both immunosuppressants and thymectomy, to determine whether the sequence and timing of treatment have influences on outcomes of MG and also to select significant predictors of prognosis.Methods It was a retrospective study which reviewed 105 patients with MG who underwent thymectomy and immunosuppressants between Januay, 2000 and December, 2013.All patients were divided into two subgroups based on their order of treatment.Thirty two patients were called as immunosuppressants-first group, and 73 patients were called as thymectomy-first group.The ratios of ideal status of two groups were compared with use of the ChiSquare test.Predictors of ideal status were analyzed by logistic regression.Results (1) After 1 year, 2 years and 5 years of intervention, the proportion of ideal status was significantly higher in the thymectomy-first group than that in the immunosuppressants-first group[(33％-50％) vs.(10％-20％), P ＜0.05].For oMG patients, after 1 year, 2 years and 5 years of treatment, thymectomy-first group had a higher ideal status rates than immunosuppressants-first group[(25％-50％) vs.(11％-18％)].But no significant difference was noted in the rates of ideal status at each follow-up time point.(2)Multivariate logistic regression analysis showed that sequence of treatment (OR =0.154, 95 ％ CI: 0.046-0.518, P =0.002) and symptom-thymectomy interval(OR =0.903,95 ％ CI: 0.835-0.976, P =0.010) were the significant predictors of ideal status.Conclusion Thymectomy prior to immunosuppressants is associated with relatively good prognosis.It is suggested that patients with gMG, or adult patients with oMG who are resistant to drug, will be better to undergo thymecotomy as early as possible.