Volume 89  ·   Issue 08  ·  2009

Refractory asthma accounts for 5% ~10% of asthma patients [1-2]. Although the proportion is not high, the frequency of emergency treatment and hospitalization is 15 times and 20 times that of mild to moderate asthma patients, respectively, which is one of the important reasons for the increase of asthma treatment cost.

Bronchial asthma (asthma) is one of the common chronic respiratory diseases. In the past 20 years, the incidence of asthma has been increasing significantly worldwide, and the reasons for the rising incidence of asthma are still not completely clear. At the same time, the incidence of overweight and obesity in the population is also increasing. According to the survey data from 1999 to 2002 in the United States, about 65% of adults aged>20 years old are overweight or obese, and the incidence of obesity has increased from 15% in 1980 to 30% in 2002 [1].

As early as the 2nd century, Galen, a famous scholar, noticed the correlation between upper and lower respiratory tracts, and proposed that abnormal nasal structure can directly cause lung diseases.In 1919, Sluder put forward the famous nasal-lung reflex hypothesis, which has far-reaching influence.Since the 1980s, with the development of cell and molecular biology, CT imaging and nasal endoscopy, the correlation between upper and lower respiratory tract inflammation has become a hotspot of scholars around the world.

In 1988, Turner-Warwick [1] reported the follow-up results of 7729 outpatient asthma patients. 94% of the patients woke up at least once a month due to an asthma attack at night, and 74% of the patients woke up at least once a week due to an asthma attack at night; Sixty-four percent of patients had three nightly asthma attacks per week, and 39% had an asthma attack almost every night.

Wheezing symptoms or asthma-like attacks caused by allergens are common in clinic, and the main diseases manifesting as allergic wheezing are bronchial asthma, allergic bronchopulmonary aspergillosis (ABPA), allergic granulomatous vasculitis, pulmonary eosinophil (EOS) infiltration and extrinsic allergic alveolitis (EAA), etc.

Objective To evaluate the status of asthma eontrol and asthma perception in asthmatic outpatients of Beijing urban district.Methods A questionnaire survey in a face-to-face setting was conducted among 360 asthmatie out.patients,144 males and 316 females,aged(48±15),from Jun 2007 to Dec 2007 in 3 class 3 first level general hospitals in 3 Beijing urban districts.Results Among 360 asthmatic patients,325(90.3%)enjoyed various kinds of social insurance.During the past year,12.2%(44/360)of them were in hospital because of asthma exacerbation,25.6%(92/360) of them had visited emergency department because of asthma exacerbation;the percentage of adults with lost workdays caused by asthma was 29.6%(65/220),and the percentage of children with lost schooldays Was 26.9%(7/26);87.8%(316/360)of the respondents had undergone a lung-function test,29.2%(105/360)had ever used peak flow meter:68.6%(247/360)of these patients had been used inhaled cortieosteroids regularly for a long time,and 30.6%(1 10/360)of them achieved asthma control.Conclusions The levels of asthma control and asthma perception among the asthma patients in Beijing have been improved a lot.The asthma perception of the patients influences the control level greatly.

Objective To enhance the knowledge about Churg-Strauss syndrome(CSS).Methods The clinical data of 16 CSS patients were analyzed.Follow-up was conducted flor 42(14-76)months.Results All patients had the symptom of asthma.As in other case series,the lung,peripheral nervous system,and skin were the most commonly involved organs.During the active stage of the disease,most of the Datients exhibited peripheral blood eosinophilia and elevated serum total IgE level.Two patients were treated with pulse treatment of methylprednisolone followed by prednisone with tapering dose and cvclophosphamide,nine patients were treated with eorticosteroids and cyclophosphamide,and the others were treated with eortieosteroids alone.Several patients were treated with the following drugs in combination:metllotrexate,hydroxychloroquine,azathioprim,ciclosporin,common Threewingnut root,and intravenous injection of IgG.Symptom relief Was seen in all patients after treatment.Two patients were lost to follow-up.Seven patients showed sustained remission,of which 3 had discontinued the medication,3 were treated with low-dose corticosteroids and immunity inhibitors,and 1 continued to be treated with low-dose corticosteroids.Six patients suffered from relapse 1.7 times due to withdrawal of eortieosteroid treatment or tapering of corticosteroid dose and they regained remission once more after increasing the corticosteroid dose and combination of cyclophosphamide.Four of these 6 patients were treated with eorti costeroids of low or mediam dose as maintenance doses,and the other 2 with medium-dose eortieosteroids and cyclophosphamide.One Datient committed suicide because of family dissension 1 year after treatment.Conclusions The clinical manifestations and course of CSS vary considerably.Its clinical manifestations may range from mild symptoms to life-threatening conditions.Corticosteroids and eyelophosphamide are both effective remedies.Despite relapses in several cases,the general prognosis is good.

Objective To explore the feasibility of the therapeutic strategy to use T-bet gene modified dendritc cells(DCs)to reverse the eourse of asthma.Methods(1)Mature DCs were derived from mononuclear cells obtained from femur of BALB/c mouse and divided into 3 groups,T-bet group transfected with recombinant adenovirus Ad-T-bet containing T-bet gene,LacZ group transfected with recombinant adenovirus Ad-LacZ containing LacZ gene,and control group.Seven days later ELISA was used to detect the interferon(IFN)-γ level in the culture fluid.(2)Airway inflammation abrogatingtrial.Twentyfour BALB/c mice were sensitized with intrapefitoneal injection of ovalbumin(OVA)(on day 1 and 15)to estabHsh asthma models,and then randomly divided into 3 equal groups:T-bet group injected intravenously with T-bet-modified Des on day 27,LacZ group injected with LacZ-modified DCs,and model control group without intravenous injeetion.Two days later the model mice began to undergo challenge by inhalation of OVA twice(on day 29-31).Eight mice were used as control group treated with PBS.On day 37 all mice were killed,ELISA was used to detect the blood intedeukin(IL)-4 and IFN-γ levels,and microscopy was conducted to observe the airway inflammation.(3)Airway inflammation reversing trial.Another 24 model mice were divided into 3 equal groups as well:re-challenged T-bet group injected intravenously with T-bet modified DCs on day 27 and 42,re-challenged LacZ group injected intravenously with LacZ-modified DCs on day 27 and 42,and model control group.Since the day 45 OVA inhalation was given once a day for successive 3 days.On day 49 these mice were all killed to undergo the tests as mentioned above.Results The IFN-γ level in the culture fluid of the T-bet gene modified DCs was(15.24±4.75)ng/ml,significantly higher than that of the LacZ gene modified DCs and control DCs[(3.08±0.61)and(2.35±0.41)ng/ml respectively,both P＜0.01].The IFN-γ in mice blood plasma of T-bet groups in abrogating and reversing trial were(130.2±10.5)and(145.7±16.7)pg/ml respectively,both significantly higher than those of the abrogating and reversing trial normal control groups[(25.0±6.5)and(24.6±5.9)pg/ml respectively],asthmatic model control groups[(20.7±4.5)and(16.5±7.0)ps/ml respectively] and LacZ groups[(17.6±7.0)and(24.2±9.0)pg/ml respectively](all P＜0.01).However,the IL-4 levels in mice blood plasma of T-bet groups were both significantly lower than those of asthmatic model control groups and LacZ groups(all P＜0.01).The airway inflammation of T-bet groups were remarkable milder than those of the model control groups and LacZ groups.Conclusion The asthma management strategy based on T-bet gene modified DCs is feasible with the plausible mechanism that the T-bet gene modified DCs regulate the T cells differentiation and polarization on the antigen presenting level.

Objective To explore the mechanism and immunoregulatory role of 1,25-dihydroxy vitamin D3[1,25(OH)2D3]-treated dendritic cells(DCs)in allergic airway inflammation.Methods Mouse bone maiTow-derived DCs were treated by 1,25(OH)2D3 for72 h.The expression levels ofdifferent Notch ligands:Jaggedl,Jtmoged2,Deltal,Delta3,and Delta4 in these DCs were detected by RT-PCR and westem blotting.Mouse spleen CIM+T cells were cultured with 1,25(OH)2D3-treated DCs or 1,25(OH)2D3-treated DCs Mocked by polyclone antibody of Jaggedl or Jagged2(control group)for48 h.The pementage of CIM4CD25+Foxp3+T cells in CD4+T cells was detected by flow cytometry(FCM).Ten mice underwent intraperitoneal injection of ovalbumin(OVA)to be sensitized and tIIen divided into 2 groups to inhale 1,25(OH)2 D3-treated DC suspension and PBS-DC suspension respectively for 6 successive days.Then the micc were killed.Bronchoalveolar lavage fluid was obtained to detect tlle eosinophil count and the levels ofinterleukin(IL)-4,IL-6,IL-13,and interferon(IFN)-γ,and pathological examination of lung was conducted.Spleens were taken out to isolate the CD4+T cells,and immunolabeling and FCM were used to detect the percentage of CD4+CD25+Foxp3+T ceils.Results The mRNA and protein expression levels of Jaggedl and Jagged2 in the 1,25(OH)2D3-treated DCs were(0.376±0.029)and(0.786±0.034),and (0.564±0.018)and(0.632±0.026)respectively,all significantly higher than those of the control group [(0.146.±0.032)and(0.124±0.025),and(0.267±0.012)and(0.098±0.012)respectively,all P＜0.01)].The percentage of CD4+CD25+Foxp3+T cells in the CD4+T cells cultured with 1,25 (OH)2D3-treated DCs was(22.49%±0.56%),significantly higher than that of the a PBS control group [(6.67%±0.50%),P＜0.01].The percentage of CD4+cD25+Foxp3+T cells in CD4+T cells after cultured with 1,25(OH)2D3.treated DC blocked by polyclone antibody of Jagged2 was(6.56%±1.89%),significantly lower than that of the un.blocked control group[(20.37%±1.64%),P＜0.01].The levels of IL-4,IL-5,IL-13,and IFN-γ,and eosinophil count in the BALF of the 1,25(OH)2D3-treated DC group were(33±5)pg/ml,(134±23)pg/ml,(91±11)pg/ml,and undeteetable(＜12.5 pg/m1),and(236±29)×103/ml.all significantly lower than those of the PBS-Dc group[(55±7)pg/ml,(332±49)pg/ml,(152±19)pg/ml,and(23±6)pg/ml,and(588±56)×103/ml,all P＜0.01].The percentage of CD4+CD25+Foxp3+T cells in the spleens of the 1,25(OH)2D3-treated DC group was(14.69%±1.14%),signifieantly higher than that of the PBS-treated DC group[(2.38%±0.14%,P＜0.01).Conclusion Treatment of the DCs with 1,25(OH)2D3 inhibits the allersic inflammation in tlle airway,maybe via the induction of CD4+CD25+Foxp3+regulatory T cells by 1,25(OH)2D3-treated DCs through Jagged2-mediated Notch signal pathway.

Objective To investigate the effects of transurethral unroofing in treatment of seminal vesicle cyst.Methods Seven patients seminal vesicle cyst 2.1 cm×3.0 cm×3.3 cm-5.5 em×6.3 cm×10.2 cm in size,aged 36(21-65),with the symptoms of hematospermia(4 cases),hematuria (3 cases),epididymitis(2 cases),dysuria(1 case),bladder irritation symptoms(1 case),bloody mucus of urethral orifice after emiction(1 case),perineal discomfort(2 case),and infertility(3 cases),underwent transurethral unroofing of seminal vesicle cyst.Results Operation was performed successful on all 7 patients.The mean operative time was 20 min,the mean estimated operative blood lOSS was 5 ml,and the mean hospital stay was 3 d.Follow.up was conduced for 28.3 months(8 months-10 years).All patients were free of symptoms after surgery,witllout recurrence and complications t11at needed further therapy.Two of the 3 patients with infertility succeeded in fertilization 1 year after surgery,and 1 patient with retrograde ejaculation underwent intracytoplasimc sperm injection and succeeded in fertilization 6 months after operation.Condusion Transurethral unroofing provides an effective approach to tlle seminal vesicle cyst witll minimal invasion,short hospitalization,and rapid recovery.

Objective To analyze the chromosomal karyotype aberrations of exfoliated urothelial cells in superficial bladder cancer patients and the correlation thereof to recurrence of carcinoma.Methods Voided urine samples were collected from 42 patients with pathologically confirmed recurrent bladder cancer and 24 bladder cancer patients without pathologically confirmed recurrence,all of which had undergone complete transurethral resection and had been followed up for more than 3 years.Fluorescence in situ hybridization(FISH)was used with Spectrum Green to label the chromosome 7 and Spectrum Red to label the chromosome 17 of the exfoliated uruthelial cells.Resuits The aneuploidy rates of chromosomes 7 and 17 were 48.5%(32/66)and 50.0%(33/66)respectively,and the co-aneuploidy rate of chromosomes 7 and 17 was 25.8%(17/66).In the patients with G2/3 superficial bladder cancer,the aneuploidy rate of chromosomes 17 of those with recurrence was 64.3%.significantly higher than that of patients without recurrence(22.2%,P＜0.05).However,there were not significant difierences in the aneuploidy rates of chromosomes 7 and 17 in the pTa and pT1 superficial bladder cancer patients with or without recurrence(all P＞0.05).however,the co-aneuploidy rate of chromosomes 7 and 17 of the patients with recurrence was 47.8%,significantly hiher than that of the patients without recurrence(12.5%,P＜0.05).F0urteen of the 42 patients with recurrence showed progression,i.e.,with increased grade or stage(≥pT2).The aneuploidy rates of chromosomes 7 and 17 of these 14 patients were 78.6%and 92.9%respectively.both significantly higher than those of the 28 patients without progression(42.9%and 46.4%respectively,both P＜0.05).Conclusion Abnormality in the chromosomes in exfoliated urothelial cells of superficial bladder cancer patients using FISH technique helps predict recurrence and progression of the cancer.

：Objective To investigatethe role of CD2-associated protein(cD2AP)and nephrin expression in the muhilocular cysticrenal cell carcinoma(MCRCC)Methods Seventy four specimens of renal lesions.including 29cases of MCRCC,32 case of clear cell renal cell carcinoma(CCRCC),and 13 cases of simplerenal cyst(SRC),were collected during operation.Immunohistochemistry was used to detecttlle CD2AP expression.Five wax lumps from each of the 3 groups of specimen,totally 15,wererandomly selected to undergo re-sectioning and immunohistochemistry so as to compare thelevels of staining intensity and location of expression of CD2AP and nephrin in the samesections.Results The expression of CD2AP in the MCRCC specimens was stronger than that inthe CCRCC that was in turn stronger tllan that than that in the simple renalcyst(SRC)specimens.The epithelium lining the cysts in MCRCC was strongly positive in CD2APcompared to other parts.CCRCC showed a weak expression of CD2AP,while CD2AP Was negativein the SRC specimens.The staining intensity and location of expression were completelyidentieal for nephrin and CD2AP among the three types of tissue specimens.ConclusiOIlS TheCD2AP expression iS much stronger in MCRCC than in CCRCC and SRC.CD2AP may be used as abiomarker in differential diagnosis of MCRCC.CCRCC.and SRC.The identical expression ofCD2AP and nephrin in MCRCC and their specific expression in podocytes are important hintsfor the mechanism of MCRCC.

Objective To investigate the characteristics of chest hiigh-resolution computed tomography(HRCT)and pathogenesis of acute graft versus host disease(aGVHD)-induced lung injury after allogenic hematopoietic stem cell transplantation(allo-HSCT).Methods Chest HRCT was performed in 47 patients with aGVHD of grade Ⅱ-Ⅳ after allo-HSCT.Twenty-four of the patients underwent different treatment regimens against aGVHD.Before the treatment peripheral blood samples were collected to detect the serum interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α).Transbronchial biopsy was performed in 4 patients that failed to recover completely after treatment.Pulmonary function was examined in the patients who survived more than 6 months in every 3 months.Resuits Twenty of tlle 47 patients showed abnormal images by chest HRCT and 17 of the 20 patients were suspected to be witll aGVHD-induced lung iniury.The HRCT images were characterized by diffused interstitial infiltrate in 5 cases.diflused intemtitial and alveolar infiltrate in 7 cases.and diffused interstitial and segmental lobar alveolar infiltrate in 5 cases.Nine cases had bilateral pleural effusion and hydropericardium,including 4 eases accompanied by myocardial hypertrophy.The levels of serum IFN-γ and TNF-α of the patients with lung injury were(6.9±1.8)μg/L and(400±102)μg/L respectively,both not significantly different from those of the patients without lung injury[(6.3±1.2)μg/L and(428±83)μg/L respectively,P=0.202,0.306].The histopathology of the lung tissue was characterized by disorganization,epithelial cell damage,interstitial fibroplasias,and interstitial T lymphocyte or macrophage infiltrate.The effective rate of treatment for aGVHD-induced lung iniury was positively correlated witll that for aGVHD(r=0.771,P=0.01).Eleven of the 24 patients who survived more than 6 months had abnormal pulmonary function.including 7 out of tlle 9 patients with aGVHD-induced lung injury and 4 out the 15 patients without aGVHD-induced lung injury.There was no significant difference in the incidence of abnormal pulmonary function between the patients with and without lung injury(P=0.033).Conclusions Lung is one of the target organs of aGVHD.IFN-γ and TNF-α may play a role in the pathogenesis of aGVHD-induced lung injury.Acute GVHD-induced lung injury may progress to late-onset non-infectiouslunginjury.

Objective To study the expression and function of sphingosine kinase(sphK)1 and SphK2 in human keloid fibroblasts.Methods Specimens of keloid and surrounding normal skin were collected from 12 patients with keloid during operation.Primary fibroblasts were isolated,cultured,and randomly divided into 3 groups:normal skin group,keloid group,and keloid with transforming growth factor (TGF)-β1 group cultured with TGF-β1 for 48 h.Immunofluorescence technique was used to detect the location of SphK1 and SphK2 protein.Real-time PCR and Western blotting were used to measure the mRNA and protein expression levels of SphKl and SphK2.Results Sphkl protein was localized primarily in the nuclei of the fibroblasts,and Sphk2 protein was detected both in the cytoplasm and nuclei in the 3 groups.The mRNA and protein levels of Sphkl in the keloid group were(0.0608±0.0190)and(0.8308±0.1093)respectively,both significantly higher than those of the normal skin group[(0.0383±0.0147)and (0.6800±0.1126)respectively,both P＜0.05],but significantly lower than those of the keloid fibroblasts with TGF-β1 group[(0.0790±0.0280),P＜0.05,and(1.4267±0.1938),P＜0.01].There was no significant differences in the Sphk2 mRNA and protein levels among these 3 groups(all P＞0.05).Conclusions Sphk1 plays a leading role in keloid pathogenesis.The SphK1 mRNA and protein levels are increased by TGF-β1 stimulation in keloid fibroblasts,perhaps indicating that Sphkl is involved in TGF-β signal transduction pathway.

objective To study the effects and role of central endocannabinoid system in the mechanism of visceral hyposensitivity induced by rapid eye movement(REM)sleep deprivation.Methods Twenty-four SD rat were divided randomly in to 3 groups:cage-yoked group(YC Group,experimental control group),REM sleep deprivation group(SD Group)exposed to REM sleep deprivation by means of flower pot technique lasting for 48 hours,and Rim Group,receiving rimonabant,a cannabinoid antagonist,after REM sleep deprivation.48 hours after the sleep deprivation abdominal eleetromyogram in response to colorectal distension(CRD)was recorded to asses t11e visceral sensitivity.Then the rats were killed with their central nervous system taken out.RT-PCR and Western blotting were used to detect the RNA and protein expression of cannabinoid receptor CBl,fatty acid amide hydrolase(FAAH),and monoaeylglyeerol lipase(MGL)in the thaiamus,brain stem,and spinal cord.Results (1)Under the pressures of 40,60,and 80 mm Hg.the abdominal electrical activity frequencies of external oblique muscle responding to CRD in SD Group were(220±94),(313±162),and(493± 279)times respectively,all significantly lower than those in YC Group[(506±223),(1053±548),and(1632±249)times respectively,all P＜0.05],and those of Rim Group were(668±257),(1144±93),and(1653±153)times respectively,all signifieantly higher than those of SD Group(a11 P＜0.05),but not significantly different from those of YC Group.(2)The RNA and protein expression levels of CB1 receptor in the thalamus,brain stem,and spinal cord of SD Group were all significantly higller than those of YC Group(all P＜0.05),while the RNA and protein expression levels of FAAH and MGL in the thalamus and spinal cord of SD Group were all significantly lower than those of YC Group(all P＜0.05).Conclusion The visceral hypesensitivity induced by REM sleep deprivation may be associated with the increase of expression of CNS endocannabinoid receptor and decrease of its metabolism.

Objeetive To investigate the influence of DNA methyltransferase(DNMT)3b on the expression of cylin D1 gene and methylation of its promoters and to investigate the function of DNMT3b.Methods Human hepatocellular carcinoma cells of the line SMMC7721 were cuhured and randomly divided into 3 groups:experimental group transfected with siRNA to silence the DNMT3b,control group transfected with control siRNA,and normal group without transfection.The transfection rate of siRNA was detected by fluorescence microscopy.MTr method was used to measure the survival rate of the SMMC-7721 cells.Western blotting and cell proliferation assay were performed to evaluate the expression of cyclin D1 and cell growth.Methylation specific PCR(MSP)was performed to investigate whether the promoter of cyclin D1 was methylated.Results F1uorescence microscopy showed that the transfection rate of siRNA was over 90%.MTr method showed that 24 h and 36 h after transfection the A value and survival rate of the SMMC7721cells of the experimental group were both significantly higher than those of the control d normal groups(all P＜0.05).Western blotting showed that the expression levels of DNMl3b and cyclin D1 of the experimental groud decreased significantly compared with the control and the normal groups.MSP showed no obvious change of the state of methylation among the 3 groups.Condusions DNMT3b may regulate the expression and the function of cyclin D1 gene in the human hepatocellular carcinoma cells,but does not change its methylation state.DNMT3b may play their role as a signal transduction element rather than as a DNA methyltransferase.

bortezomib is the first proteasome inhibitor successfully applied in clinic.In phase II clinical trials of bortezomib in the treatment of relapsed/refractory multiple myeloma (MM), the total effective rate reached 30% ~37%. The emergence of bortezomib is one of the important advances in the treatment of MM in recent years [1,2]. The most common adverse reactions of bortezomib include weakness (65%), nausea (64%), diarrhea (51%), decreased appetite (43%), constipation (43%), thrombocytopenia (43%), peripheral neuritis (37%), fever (36%), vomiting (36%) and anemia (32%), etc. These side effects are mostly mild and easily tolerated [1-3].

In recent years, most patients with bronchial asthma, especially mild and moderate patients, responded well to the standardized treatment of inhaled glucocorticoids and long-acting β 2 receptor agonists, but about 5% ~10% of patients still had difficult symptoms to control after standardized treatment. These patients belonged to refractory asthma [1].

Clinical data The patient was a 23-year-old female, unmarried. She was admitted to hospital on May 15, 2008 due to cough for 25 days, wheezing after activity for 20 days, and aggravation with low fever for 5 days. The patient felt sore throat and cough after participating in long-distance running 25 days before admission, without sputum and fever. 20 days before, she had wheezing after activity, which was obvious when going upstairs or walking quickly, and could be relieved by rest. She could fall asleep on her back at night without waking up with wheezing.

On November 10, 2008, the "First National Academic Conference on Childhood Syncope" co-sponsored by Peking University First Hospital and Chinese Medical Physicians Association was held in Beijing. Nearly 170 representatives from 15 provinces and cities in China attended the conference. Experts and representatives participated in the conference had special exchanges on the current status and prospects of clinical and basic research on childhood syncope.

Since the application of 7-valent pneumococcal conjugate vaccine (PCV7) to children in 2000, the incidence of invasive pneumococcal disease has decreased in both children and adults, but the preventive effect of PCV7 on pneumococcal meningitis is still unknown.

The national survey of schistosomiasis in China showed that the incidence of human schistosomiasis infection in endemic areas did not change significantly from 1995 (4.9%) to 2004 (5.1%). In 2004, the State Council set two goals for the national schistosomiasis control program: First, by 2008, all counties where Schistosoma japonicum is endemic (including 110 counties where the infection rate exceeds 5%) will reduce the human infection rate to below 5%.

Atypical neuroleptics have largely replaced typical neuroleptics in clinical practice because patients with typical neuroleptics have a higher risk of developing severe ventricular arrhythmias and sudden cardiac death, but little is known about their cardiac safety.

left ventricular apical ballooning syndrome is another acute cardiac syndrome proposed in recent years. At present, there are few reports in China. One case was admitted to our hospital, and the report is as follows.

A 19-year-old male was admitted to hospital for two repeated fractures 8 years ago, slow movement for 1 year, aggravated with intermittent convulsions for 2 weeks. In 1999, he suffered from two femoral fractures due to falls, and then found that the left leg was flexed. In 2002, he was admitted to our hospital with weakness of both lower limbs. The blood routine: red blood cells 3.71×1012/L, white blood cells 1.61×109/L and platelets 60×109/L, all of which were lower than normal. Alkaline phosphatase 571 U/L (normal value 80~150), blood calcium 2.15 mmol/L (2.15~2.55).