Background::In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as "cheese sign". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods::A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related White Matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities.Results::A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120, P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983, P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259, P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity. Conclusions::The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

ObjectiveTo analyze the functions， formulae， dosage forms， and methods of administration of the menstruation-regulating Chinese patent medicines included in the 2020 edition of the Chinese Pharmacopoeia， so as to provide reference for rational clinical use. MethodThe relevant Chinese patent medicines were recorded one by one， and the efficacy， dosage forms， methods of administration， and contraindications were counted， classified， and summarized. Further， we analyzed the Chinese medicines used in these Chinese patent medicines， identified the high-frequency Chinese medicines for menstrual regulation， and analyzed their natures， tastes， meridian tropism， and functions， aiming to guide the clinical use. ResultA total of 142 Chinese patient medicines for menstrual disorders were included in this study. They were classified into 12 categories according to their efficacy， mainly for regulating menstruation and blood， tonifying， activating blood， and eliminating mass. The representative Chinese patent medicines were Bazhen Yimu pills， Shaofu Zhuyu pills， Lyujiao Buxue granules， and Guizhi Fuling pills， which are in line with the principles of moving Qi and blood and regulating liver and spleen. Menstruation-regulating Chinese patents medicines are mostly in pills and capsules and are mainly taken with yellow wine or ginger decoction. Pregnancy was the contraindication with the highest frequency， followed by menstruation and dietary precautions. The high-frequency Chinese medicines mainly had the functions of tonifying， activating blood， resolving stasis， and clearing heat， with the top three being Angelicae Sinensis Radix， Paeoniae Radix Alba， and Chuanxiong Rhizoma. These medicines mainly had warm nature， sweet， bitter， and pungent tastes， and tropism to liver and spleen meridians. ConclusionThe treatment of menstrual disorders should focus on nourishing and activating blood， regulating Qi， tonifying kidney， supporting spleen， nourishing liver， and harmonizing stomach. The appropriate dosage form should be selected according to the patient's specific conditions. The medicinal guide and the method of administration should be selected on the basis of syndrome differentiation with attention to the contraindications. In summary， the Chinese patient medicines for menstrual regulation should be chosen based on the patient’s syndrome under guidance of the theory of traditional Chinese medicine.

With high incidence and lethality rate and certain disability rate， tumor has become a major global public health threat. It has been verified that the occurrence and development of tumor are resulted from the synergy of environment， heredity， and gene mutation， involving the abnormal activation or inhibition of a variety of related pathways such as oxidative stress， inflammation， autophagy， and mesenchymal transition of cells. Among them， the excessive activation of inflammatory signaling pathway is one of the main mechanisms of carcinogenesis and tumor progression， which enhances the proliferation， chemoradiotherapy resistance， invasion， and metastasis of cancer cells. At the moment， the correlation between long-term chronic uncontrollable inflammation and "inflammation-cancer transformation" has been widely recognized. Therefore， it is of great significance for the prevention and treatment， diagnosis， and prognosis evaluation of tumor to clarify the role of inflammation in the incidence of tumor. Blockers or activators have been developed to target the corresponding inflammatory pathways. However， tumor is accompanied by the abnormality of multiple inflammatory pathways， especially the advanced tumor with metastasis of cancer cells， and thus the efficacy of single pathway-targeting agents is non-ideal. Chinese medicine， featuring multiple components and multiple targets， can remarkably control the inflammatory response， delay tumor progression， enhance the sensitivity of tumor cells to radiotherapy and chemotherapy， and reduce postoperative infection and the adverse reactions caused by radiotherapy and chemotherapy， thereby exerting the anti-cancer effect. Nevertheless， a few reports on the anti-tumor effect of Chinese medicine from the perspective of inflammation are available. Therefore， this paper mainly expounds the influence of inflammation on the occurrence and development of tumor and summarizes the research on the intervention of tumor by Chinese medicine through inflammatory pathway， which is expected to provide a new mindset for the prevention and treatment of tumor.

Objective: To evaluate the value of cerebrospinal fluid markers expecially total-tau protein (T-tau), phosphorylated-tau protein (P-tau) in diagnosis and differentiation of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: sCJD (according to 2009 Brain criteria, 2018 Neurology amended criteria), Alzheimer's disease (AD; the National Institute on Aging at National Institutes of Health and the Alzheimer's Association revised guidelines 2011 criteria) and other patients without cognitive impairment, matched for sex and age, in the Department of Neurology, Peking Union Medical College Hospital from 2018 to 2019 were enrolled. Twelve sCJD patients, 49 AD patients and 14 normal controls were enrolled. Cerebrospinal fluid (CSF) specimens were collected through gravity dropping directly, and further stored in -80 ℃ and disposed according to widely used standards. The levels of T-tau and P-tau were measured by ELISA. The data on electroencephalogram and neuroimaging findings of sCJD patients were recorded. Moreover, specimens of sCJD patients were sent to the Chinese Center for Disease Control and Prevention to test 14-3-3 protein and PRNP genotype. Results: Using Mann-Whitney U test, T-tau concentrations were found higher in patients with sCJD (1 211(448, 2 227) pg/ml) than in AD patients (549(314, 1 078) pg/ml; U=178, P=0.034 9), and both groups had higher T-tau than the control group (127(79, 192) pg/ml; U=20, 73, P<0.01). The level of P-tau was significantly increased in AD patients (72(58,109) pg/ml) compared to the control group (27(15, 42) pg/ml; U=82, P<0.01), but not in sCJD patients (32(24, 47) pg/ml). The T-tau/P-tau ratio was higher in sCJD patients (29.77(20.01, 54.53)) than in AD patients (7.45(4.79, 10.43); U=87, P<0.01). Twelve sCJD patients had cotical hyperintensity on diffusion weighted imaging and five had periodic three-phase waves on electroencephalogram. Nine sCJD patients, whose CSF samples were tested in the Chinese Center for Disease Control and Prevention, carried an M/M genotype at codon 129 and E/E at codon 219. Conclusion The CSF tau level and T-tau/P-tau ratio are significantly increased in sCJD, which may promote the diagnosis and differentiation of sCJD in routine clinical setting.

OBJECTIVE: To study the long-term efficacy and safety of CD19 chimeric antigen receptor T cells (CAR-T) in the treatment of relapsed patients with B-cell acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 7 patients with B-cell ALL relapsed after allo-HSCT were treated with CD19 CAR-T cells from September 2015 to March 2018. Among them, 6 had hematological recurrence and 1 had positive of MRD. They all were treated with a single infusion of CAR-T cells. FC chemotherapy regimen was administered before transfusion. The median number of CAR-T cells transfused was 6.0 (range 4.0-8.6) )×10/kg. Long-term efficacy and toxicity were evaluated. RESULTS: Bone marrow examination performed at d 30 after CAR-T infusion showed that all 7 patients achieved complete remission and MRD negative, grade I CRS for 1 case and grade II CRS for 6 cases, two of them had mild neurotoxicity, which was controlled by treatment. Two patients presented grade VI intestinal GVHD after CAR-T infusion. The median follow-up time was 18 months (range 12-42). Follow-up showed that two patients relapsed at 9 months and 14 months after treatment, out of 2 patients one died of progressive disease and the other reachived the hematological remission, but MRD was positive after CD22 CAR-T cell therapy. At present, five patients are disease-free survival, moreover showed complete donor chimerism. One year after CAR-T cell therapy, the results of immune reconstitution showed that CD4 level was more than 300×10/L in 5 patients who disease-free survived. Among them, 3 patients had poor recovery of immunoglobulin and received gamma globulin replacement therapy. CONCLUSION All patients are followed up for at least one year. The preliminary efficacy and safety are satisfactory. CAR-T cell infusion is an effective method for the treatment of B-ALL recurrence after allo-HSCT.
B-Lymphocytes ; Hematopoietic Stem Cell Transplantation ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Receptors, Chimeric Antigen ; T-Lymphocytes

Objective To analyze the clinical and histology characteristics of a patient with frontal lobe epilepsy diagnosed with mild malformation of cortical development with oligodendroglial hyperplasia, and to recognize the new neuropathological entity. Methods Clinical history, seizure types, neuroimaging, electroencephalography as well as macroscope, histology and immunohistochemistry characteristics were collected from a frontal lobe epilepsy patient and were compared with cases from literature. Results It was a female patient aged 16 years with 12 years history of epilepsy. The seizures manifested as episodes of conscious loss with automatism including grope and voice lasting for seconds. About 10 episodes a day were found and sometimes with secondary generalized tonic-clonic seizures. MRI showed blurring of grey-white matter interface in left orbital frontal cortex. Video-encephalography revealed left frontal lobe origin of seizures. So left prefrontal lobe was removed. Histology showed almost normal cortex neuropil and neurons. Blurring of grey-white interface in some area with patches of proliferation of oligodendrocytes in the corresponding sub-cortical white matter was found. The density of oligodendrocytes was significantly higher in sub-cortical than in deep white matter both shown in HE and Oligo-2 staining. Obvious oligodendrocytes increase and satellite phenomenon in deep cortical layer as well as increased ectopic neurons in sub-cortical white matter were found in the lesion. In proliferation area, there were some nuclei stained with Ki-67, but not as high as tumor. Subsequent follow up for two years proved the operation efficacy and benign prognosis. Conclusions There are special and undiscovered histopathological entities in epilepsy etiology. Although known as grey matter disease, white matter pathology plays an important role in epilepsy pathophysiology which needs further research.

BACKGROUND:Transforming growth factor β1 (TGF-β1) and interleukin 1β (IL-1β) have been reported to play an important role in the occurrence and development of primary osteoarthritis. OBJECTIVE:To investigate the association between gene polymorphisms of TGF-β1 and IL-1β and primary knee osteoarthritis. METHODS: Han and Uyghur elderly populations in Xinjiang Uygur Autonomous Region, China were surveyed on the prevalence of osteoarthritis, followed by allotted to osteoarthritis and health groups according the symptoms and radiography. Genotyping TGF-β1-509C/T and -1348C/T and IL-1β-511C/T was performed to analyze the relationship between the gene polymorphisms of TGF-β1 and IL-1β and osteoarthritis. RESULTS AND CONCLUSION:Alleles T and C with genotypes CC, CT and TT were detected in both two groups. In the Uygur population, the genotype frequency of TGF-β1-509C/T and IL-1β-511C/T showed significant difference between osteoarthritis and health groups (P < 0.05). In the Han population, the genotype frequency of TGF-β1-1348C/T showed significant difference between two groups (P < 0.05). These results suggest that the Uygur individuals carrying TT genotype of TGF-β1-509C/T and IL-1β-511C/T, and Han people carrying the TT genotype of TGF-β -1348T are more susceptible to osteoarthritis.

OBJECTIVETo evaluate the relationship between T lymphocyte subsets and the incidence of graft-versus-host disease (GVHD) and its clinical significance of monitoring the changes of T lymphocyte subsets dynamicly on 1, 3, 6, 12 month after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSTwenty cases received allo-HSCT in Department of Hematology of General Hospital of Beijing Military Command from January 2013 to January 2014, including 10 males and 10 females with average age of 20.3 years (3-46 years old), among them 4 cases rectived HLA matched transplantation and 16 cases rectived HLA mismatched transplantation. The levels of T lymphocyte subsets including CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), CD4(+)CD25(high) FOXP3(+) in the peripheral blood were manitored with flow cytometry (FCM) on +1, +3, +6, +12 month after transplantation dynamicly.

RESULTS(1) Follow up to March 2015, the levers of CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), CD4(+) CD25(high) FOXP3(+) showed a different degree of recovery after transplantation for all cases and returned to the lever of pre-transplantation on 12 month basically, and CD8(+) T cells recovered earlier than CD4(+) T cells, while the decrease of CD4(+) T cells lasted more than 1 year; The proportion inversion of CD4(+)/CD8(+) also lasted for more than 1 year;(2) The level of CD4(+) CD25(high) FOXP3(+) in patients with acute GVHD was lower than that in patients without acute GVHD.

CONCLUSIONThe dynamic monitoring of the T lymphocyte subsets, especially CD4(+) CD25(high) FOXP3(+) after transplantation has importent clinical significance, it can forecast the incidence of acute GVHD before symptoms appeared; the dynamic monitoring of the T-lymphocyte subsets also can be used as reference indicator for prediction of GVHD, theraby it can reduce mortality of patients after transplantation.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; T-Lymphocyte Subsets ; cytology ; Young Adult

Objective To explore the walking ability and cognitive function changes in normal pressure hydrocephalus patients after cerebrospinal fluid ( CSF ) tap test for helping clinicians choose evaluation time and methods.Methods Twenty-seven patients with probable normal pressure hydrocephalus in Peking Union Medical College Hospital from 2013 to 2014 were included.All patients were evaluated using Minimum Mental State Examination, the Montreal Cognitive Assessment, Ability of Daily Life, and Idiopathic Normal Pressure Grade Scale, underwent 1.5 T head MRI scan and had ventriculo-peritoneal shunt after informerd consent.A lumbar tap with removal of 30 ml of CSF was performed in all patients.Evaluations included the 10 m walking time and steps, Trail Making Test A, number code and Stroop test.Those tests were performed 1 day before and 4, 8, 24, 72 hours after CSF tap test.The walking test and neuropsychological test results were compared between those before and after the CSF tap test.Correlation analysis was conducted between the normal pressure hydrocephalus featured MRI characters and CSF tap test responses including Evan′s index, callosum corpus angle, mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure associated with ventriculomegaly . Results Compared with 0 h walking time (23.56(14.00) s), the 10 m walking time on the 8 hours and 24 hours after CSF tap test, which were 19.41 ( 9.00 ) s and 19.67 ( 11.00 ) s respectively, were significantly improved ( Z values in Wilcoxon signed ranks test were -3.416 and -3.443 respectively,both P<0.01).There were no statistically significant differences on every evaluation time point.The neuropsychological tests changings were significant on 24 hours and 72 hours.Compared with 0 h neuropsychological test z scale (-10.28(21.60)), the z scale on the 24 hours and 72 hours after CSF tap test, which were -6.29 (26.72), -3.37(36.15)respectively, were significantly improved (Z values in Wilcoxon signed ranks test were -3.506,-2.701 respectively, both P<0.01).The Evan′s index, callosum corpus and the feature of mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure were not statistically correlated with the response of CSF tap test.Conclusions Walking ability in normal pressure hydrocephalus patients was improved after the CSF tap test.The Evan′s index, callosum corpus and the feature of mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure might not be correlated with the response of CSF tap test.

This study was aimed to explore the effect and feasibility of reduced conditioning intensity allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed ETO positive acute myeloid leukemia (AML) patients. Fifteen cases of relapsed AML received the reducing conditioning intensity allo-HSCT from January 2011 to January 2013 in Beijing Military Command General Hospital. All patients were high-risk type of relapsed or refractory AML, including 10 males and 5 females, aged from 16 to 48 years old with mean age of 32.5 years. Ten cases are HLA-identical matching and other 5 cases are HLA-haploidentical.donors received granulocyte colony-stimulating factor (G-CSF) to mobilize the peripheral blood stem cell for transplantation. Conditioning regimen was fludarabine combined with busulfex, cytarabine and cyclophosphamide. The preventive donor's peripheral blood stem cell infusion were performed after 3 months of transplantation, and the toxicity, GVHD and disease-free survival were observed in patients after transplantation. The results showed that all patients achieved hematopoietic reconstitution, the average time of neutrophils ≥ 0.5 × 10⁹/L and platelets ≥ 20 × 10⁹/L were 15.5 d and 16.8 d respectively. Implantation was confirmed by the evidence of 100% donor hematopoiesis. Follow-up to June 2014, with a median follow-up duration of 27.5 months (18-54 months), GVHD occurred in 8 cases of all patients, one died of complication, the other 4 cases died of relapse and the other three patients remained in disease-free survival. The disease-free survival rate of 2-year was 66.7%,the longest disease-free survival time was up to 54 months. It is concluded that the reduced conditioning intensity allo-HSCT is the effective and safe method for relapsed AML with ETO-positive, and it may be chosen as a treatment method for relapsed ETO positive AML patients.
Adolescent ; Adult ; Allografts ; Cytarabine ; Disease-Free Survival ; Erythropoietin ; analysis ; Female ; Granulocyte Colony-Stimulating Factor ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; therapy ; Male ; Middle Aged ; Transplantation Conditioning ; Vidarabine ; analogs & derivatives ; Young Adult