Volume 91  ·   Issue 46  ·  2011

Positive pressure mechanical ventilation is the most effective conventional supporting treatment for respiratory failure at present, which can meet the ventilation and oxygenation needs of most patients. However, for patients with extremely severe respiratory failure and some patients with end-stage lung disease who need lung transplantation, conventional positive pressure ventilation is often difficult to maintain satisfactory ventilation and oxygenation. At the same time, because the above-mentioned patients need high airway pressure and high oxygen concentration for a long time, their risk of ventilator-related complications is much higher than that of general respiratory failure patients. For patients with severe complications and complications of mechanical ventilation, positive pressure ventilation is often in an awkward situation of ignoring one thing and losing the other. In the end, most of these patients die due to refractory hypoxia, severe CO2 retention, severe mechanical ventilation complications, etc. Therefore, many scholars have been looking for another more effective and safer respiratory support method to replace traditional positive pressure ventilation, so as to avoid the above clinical dilemma. In recent years, extracorporeal membrane oxygenation (ECMO) The technology is increasingly mature, which brings new hope for patients with extremely severe respiratory failure [1].

Vision, vestibular sensation and proprioception work together to maintain the balance of human body.In the process of diagnosis of vertigo, vestibular examination not only includes the testing of vestibular function, but also includes the localization of nerve reflex pathway and the diagnosis of vertigo disease.Vestibular examination needs to be comprehensively analyzed by combining medical history and physical examination results to obtain the damaged ear lateral,the specific parts of lesions such as cochlea,vestibular (balloon,elliptical sac, semicircular canal), vestibular nerve (vestibular superior nerve,vestibular inferior nerve), central (vestibular nucleus, cerebellum and other structures) and the related information of nerve pathways related to disease damage.When some vertigo diseases are complicated, clinical symptoms are atypical or combined with multiple related diseases,the application of vestibular examination is very important for the diagnosis and differential diagnosis of diseases.

Objective To evaluate the importance of re-examinations in the diagnosis of benign paroxysmal positional vertigo(BPPV)and its clinical characteristics.Methods The medical records of 288 BPPV patients treated during January 2009 to December 2010 were reviewed and analyzed.The definite diagnosis was established by re-examinations.Results Among them,39(13.5％)were diagnosed by reexaminations or return visits.And 25 patients received a correct diagnosis on the first visit and 14 were diagnosed on return visits.Their ages,gender distribution and the times of particle-repositioning maneuver were the same as the overall profiles.The rate of horizontal semicircular canal BPPV was higher in the 39 reexamined patients than the overall rate(46.15％ vs 22.22％).And the latencies decreased during the second examination in 18 patients.Condusion Re-examinations and return visits are useful for diagnostic clarifications in the suspected BPPV patients.

Objective To explore the clinical characteristics and possible pathological mechanisms of vertigo due to enlarged vestibule with lateral semicircular canal dysplasia.Methods A retrospective review was conducted for 5 cases of peripheral vertigo due to enlarged vestibule with lateral semicircular canal dysplasia.Their characteristics of medical history,precipitating factors,course of vertigo,auditory tests,vestibular tests and imaging examine results were analyzed.Results The clinical characteristics were as follows.(1)Specifics of medical history:4 cases suffered delays in gross motor development and potential equilibrium dysfunctions.One case failed to recount an earlier medical history,but could maintainnormal hearing and vestibular functions for a long time in adulthood.(2)Most cases could identify the precipitating factors of initial attacks,such as head-bumping,nose-blowing and constipation,etc.resulting in sudden rises of intracranial or abdominal pressures.(3)Paroxysmal vertigo and progressive hearing loss were mimicking Meniere disease or large vestibular aqueduct syndrome.But its course of vertigo was different from those of Meniere disease and large vestibular aqueduct syndrome with regards to hearing levels and audiograms.(4)Some cases had positional vertigo.But the results of Dix-Hallpike and Roll tests were different from benign paroxysmal positioning vertigo(BPPV).(5)The inner ear imaging showed enlarged vestibule with lateral semicircular canal dysplasia.Conclusion The enlarged vestibule with lateral semicircular canal dysplasia is a rare etiology of peripheral vertigo.The history of delays in gross motor development and potential equilibrium dysfunctions in childhood may offer important diagnostic clues.And audiological and vestibular tests,high-resolution computed tomography and magnetic resonance may help to ascertain the diagnosis.

Objective To explore the positive visualization rate of endolymph space in Meniere's disease(MD)by three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging(3D-FLAIR MRI)and assess its diagnostic value of MD.Methods 3D-FLAIR MRI was performed at 24 h after an intratympanic injection of gadolinium diethylenetriamine penta-acetic acid in 51 MD patients.Then the examination results were summarized,analyzed and compared with those of vestibular evoked myogenic potential(VEMP)and glycerol tests.Results Gadolinium was found in perilymph inside inner ear.Furthermore the border between perilymph and endolymph was visible so that endolymphatic space was distinctly visualized on 3D-FLAIR MRI.Forty-nine(96.1％)patients demonstrated the signs of endolymphatic hydrops.Statistically significant differences existed between the results of 3D-FLAIR MRI and those of VEMP and glycerol tests(P ＜ 0.05).No complication of tympanic membrane perforation or infection was observed.Conclusion After an intratympanic injection of gadolinium,3D-FLAIR MRI has a higher positive rate in MD patients.Though as an invasive procedure,it has fewer side effects and will become an important diagnostic tool for MD.

Objective To explore the probable unsuccessful reasons for transurethral resection of bladder neck(TUR-BN)of female bladder neck sclerosis.Methods Thirty eligible cases received urodynamic inspections at pre-operation,post-operation of months 1,2,3 and 6 and year 1.Results TURBN was effective in 27 patients(90％),but ineffective in 3(10％).Among the effective cases,the urodynamic parameters of Qmax and Qave increased(P ＜ 0.05)while the residual urine volume and maximum pressure of detrusor contraction decreased(P ＜ 0.05).The above four parameters showed no difference in those ineffective cases(P ＞ 0.05).Conclusion TUR-BN is an effective therapy for female bladder neck sclerosis.Those ineffective cases are probably caused by functional obstruction.Further urodynamic imaging studies may help to confirm the causes.

Objective To explore an ideal urine drainage method and new urethral secretions of hypospadias repair.Methods The authors retrospectively analyzed 864 cases of hypospadias undergoing hypospadias repair and different post-operative urine drainages.The patients were divided into 5 groups based on the methods of urine drainage.Results The rates of such complications as cystospasm,infection of incisional wound and urinary fistula were as follows:modified method group:2.86％,3.33％,1.90％ ; 3-tube method group:10.77％,11.54％,8.46％; He's method group:20.89％,15.04％,9.75％;traditional method group:36.25％,41.25％,37.50％ ; 1-tube method group:56.47％,58.82％,48.23％.The modified method was significantly better than all the other four methods(P ＜ 0.05).Conclusion As an ideal drainage method of urine and new urethral secretions of hypospadias repair,the modified method boosts the success ratio of hypospadias repair.

Objective To explore the expression of stromal cell derived factor-1(SDF-1)and its receptor CXCR4 in myelodysplastic symdromes(MDS).Methods A total of 59 patients with a diagnosis of MDS were divided into low-grade(n =33)and high-grade(n =26)groups according to international prognostic scoring system(IPSS).Bone marrow(BM)samples were collected.The SDF-1 and VEGF levels in BM plasma,CXCR4 expression on BM CD34 + cell and the apoptosis of CD34 + cells were measured.Results The SDF-1 levels in MDS patients were significantly higher than those of normal controls [(689 ± 190)ng/L,P ＜0.05].And the low-grade group was significantly higher than that of high-grade group[(2301 ± 413)vs(1173 ± 501)ng/L].CXCR4 expression on CD34 + cells were significantly higher in high-grade group(68.1％ ± 18.8％)than that of both low-grade(21.0％ ± 9.7％)and control groups (19.4％ ± 5.3％)(P ＜ 0.05).Apoptotic rate of CD34 + cells were 54.8％ ± 10.2％ in low-grade group,24.3％ ±7.9％ in high-grade group and 18.5％ ±8.7％ in control group.It significantly increased in lowgrade group versus other groups(P ＜0.05).VEGF levels were significantly higher in MDS patients in lowgrade group[(286 ±97)ng/L]and high-grade group[(407 ± 168)ng/L]versus control group[(157 ±46)ng/L,P ＜0.05].A positive correlation was found between apoptosis of CD34 + cells and SDF-1 levels in low-grade group(r =0.805,P ＜ 0.05),VEGF levels and CXCR4 expression rate in high-grade group(r =0.683 P ＜ 0.05).Conclusion The exnression of SDF-1/CXCR4 is significantly abnormal in MDSpatients.And it is correlated with apoptosis and angiogenesis.Intervention of SDF-1/CXCR4 axis may provide a new therapeutic target.

Objective To examine the level of circulating soluble CXC-chemoline ligand 16 (CXCL16)in different types of coronary artery disease and its association with severity of disease.Methods A total of 204 male elders,aged 60-92 years old,were recruited and divided into control group(n =40),stable angina pectoris group(SAP,n =80)and acute coronary syndrome group(ACS,n =84).enzymelinked immunosorbent assay(ELISA)was used to examine the concentration of serum soluble CXCL16.Results As compared with the control(1.87 mg/L)and SAP groups(2.01 mg/L),CXCL16 level was significantly increased in ACS group(2.35 mg/L)P =(0.001,0.026).Correlation analysis showed that CXCL16 was associated with age(r =0.152,P =0.038)and C-reactive protein(CRP)(r =0.270,P ＜0.001).When categorizing CXCL16 into quartiles,logistic analysis adjusted for age and CRP showed that the higher CXCL16 concentrations significantly increased the risk of ACS but not SAP.The odds ratio of group Ⅳ OR(95％ CI)were 7.91(2.41-21.54)versus group Ⅰ as reference in ACS.Conclusion The elevated level of circulating soluble CXCL16 is associated with severity of disease in male elder ACS patients.

Objective To investigate the expression pattern of stereotyped B-cell receptor(BCR)and its prognostic significance in Chinese chronic lymphocytic leukemia(CLL)patients and evaluate the relationship to other prognostic markers.Methods Multiplex polymerase chain reaction(PCR)was used to identify the immunoglobulin vaiiable heavy-chain(IGHV)segment and its mutation status in 116 CLLpatients from April 1992 to April 2010.For CDR3-driven clustering,all in-frame IGHV-D-J rearrangements were aligned by the multiple sequence alignment software ClustalW2.Results There were 102 of 116 samples from newly diagnosed CLL were successfully analyzed.IGHV CDR3 genes were identified in 73/102 cases.Fourteen patients(19.2％)carried stereotyped BCR.A high percentage of carried stereotyped BCR was observed in 1GHV non-mutated group versus mutated group(40.9％ vs 11.8％,P =0.005).Patients with stereotyped BCR had a higher frequency of deletion(17q)(33.3％ vs 10.7％,P =0.045).The median progression-free survival(PFS)in patients with stereotyped BCR was much shorter than other patients(39 vs 84 months,P =0.002).Conclusion The patients with stereotyped BCR have a poor prognosis.It highlights the importance of immunoglobulin mediated stimulation in the development of CLL.

Objective To summarize the clinical experiences and indications of extracorporeal membrane oxygenation(ECMO)for severe ARDS caused by novel 2009 influenza A(H1N1)virus.Methods All ECMO cases with severe ARDS associated with novel 2009 influenza A(H1 N1)virus were analyzed in 5 intensive care units(ICUs)from 5 different hospitals in Beijing and Tianjin.A physician experienced in ECMO handling collected the relevant data,including general conditions pre and postEMCO,efficacy and complication parameters,ventilator settings of mechanical ventilation and clinical outcomes.The statistical software of SPSS(version 11.5)was used for data analysis.Results 18 cases of novel H1 N1 influenza with severe ARDS received ECMO.There were 9 males and 9 females(all pregnant).The mean age was(33 ± 11)years old.Eight were complicated with pulmonary barotraumas(6 of pneumothorax).Prior to ECMO,the patients underwent noninvasive and invasive positive pressure ventilation for 1 day and 60 hours respectively.Physiological parameters 2-6 hours prior to ECMO use were:(53 ± 14)mm Hg of PaO2/FiO2,(17 ± 5)cm H2O of positive end expiratory pressure(PEEP),3.80 ± 0.29 of Murray lung injury score,(7.38 ±0.10)of arterial pH,(3.3 ±2.3)mmol/L of serum lactate,16 ±8 of APACHE Ⅱ score.All patients treated venous-venous ECMO(VV-ECMO)for a mean duration of 8 days(range:2-168).Settings of mechanical ventilation(prior to ECMO vs 2 hours postECMO)were:peak airway pressure(31 ±7)vs(25 ±6)cm H2O,respiratory rate(15 ±4)vs(22 ±6)breaths/min,FiO20.8-1.0 vs 0.35-0.50,PEEP(16 ± 5)vs(12 ± 4)cm H2O.Arterial blood gas (pH,PaO2 and PaCO2)Post-ECMO of 2 hours and 24-hour significantly improved(P ＜ 0.05).Severn patients died during ECMO,11 patients were successfully weaned from ECMO.And 8 of them survived and were discharged.One patient stayed in ICU and 2 died in ICU.Conclusions As an effective measure of respiratory supports,ECMO may provide pulmonary rest and improve gas exchanges in severe ARDS induced by novel H1N1 Influenza.

Objective To investigate the glycemic control and the related factors of type 1 diabetic patients in Guangdong Province.Methods Medical records and blood samples of type 1 diabetic patients were collected in 89 tertiary and secondary hospitals from all of the 21 cities in Guangdong Province.The clinical data were analyzed to explore the correlates of glycemic control.HbA1 c levels,measured in Guangdong Diabetes Center,were used to assess glycemic control.Results 851 patients were enrolled from August 6,2010 to May 25,2011.There were 408 males and 443 females.The median(interquartile range)age was 29.6 years(20.3-41.3 years).The onset age of diabetes was 25.3 years(15.7-35.5years).The disease duration was 3.3 years(1.0-7.3 years).The BMI was 19.9 kg/m2(17.9-21.8 kg/m2).HbA1 c levels were 8.6％(6.9％-11.0％)and only 234(27.50％)patients reached the agespecific target levels.Correlates with poorer glycemic control were 13-19 years old(vs 7-12 and ≥20years old),lower household income,not on dietary intervention,never accepting diabetic education and shorter diabetic duration.Conclusion The majority of Guangdong type 1 diabetic patients did not achieve target values for glycemic control,indicating an urgent need for comprehensive management to improve glycemic control.

Objective To explore the effects of pretreatment of carbopol-encapsulated rapamycinloaded nanoparticles(RPM-NP)on vein graft stenosis in a rabbit vein graft model.Methods A segment of common carotid artery was replaced with a segment of external jugular vein in 40 rabbits.They were separated into four treatment groups,i.e.Group A:vein grafts were pretreated with intraluminal RPM-NP perfusion; Group B:peripheral venous veins were injected with RPM-NP; Group C:vein grafts received an equivalent perfusion of empty vehicle; Group D:vein grafts received no treatment.At Day 28 postoperation,the grafts and normal veins were harvested for histological examinations to analyze the indicators of intimal thickness,internal diameter,intimal/media thickness ratio and collagen volume index.Results At Day 28 post-operation,the intimal/media thickness ratios were 0.26 ± 0.02,0.73 ± 0.05,0.71 ± 0.04,0.69 ±0.03 and 0.24 ±0.01 in Groups A,B,C and D and the normal vein; the collagen volume index 0.24±0.03,0.56±0.06,0.53 ±0.07,0.49 ±0.08 and 0.21 ±0.01 respectively.Compared with the normal veins,the pathological indicators of vein graft intimal thickness,internal diameter,intimal/media thickness ratio and collagen volume index had significant differences in Groups B,C and D(all P ＜0.05).But there were no significant differences among 3 groups(all P ＞0.05).Compared with the normal vein,the parameters of vein graft intimal thickness,internal diameter,intimal/media thickness ratio and collagen volume index had no significant difference in Group A(all P ＞0.05).But as compared with other groups,these indicators had statistical significant difference in Group A(all P ＜ 0.05).Conclusion The local pretreatment of isolated vein with rapamycin nanoparticles may inhibit neointimal hyperplasia and prevent effectively vein graft stenosis.

Objective To investigate cardio-myogenic differentiation potential of human amniotic fluid colony derived stem ceils(HAFCDSC)in the form of embryonic body(EB)-like structure in vitro.Methods HAFCDSC were isolated from second trimester amniotic fluid which was backup of amniocentesis specimens.The forth passage of HAFCDSC were cultured by hanging-drop preparation in complete medium for 5 days to form EB-like structures followed by inducing medium in regular tissue culture dishes for 2 weeks(experiment group).The EB-like structures cultured in complete medium were served as conrol group.Cardiomyocyte phenotypes were detected by RT-PCR and immunofluorescence staining.Results HAFCDSC could form EB-like structures 24 h after hanging drop culture,and the diameter of EB-like structures gradually increased with culture duration and the mean diameter of EB-like structures reached 237.3-26.7 μn on 5th day.The formation rate of EB-like structures was 93.5％.RT-PCR analysis showed EB-like structures expressed stem cell related mRNA.Immunofluorescence staining demonstrated that some cardiomyocyte phenotypes such as Desmin,t-Actinin and Tn I were expressed by HAFCDSCs in EB-like structures after cardio-myogenic induction.Cardiomyocytes specific mRNA includingDesmin,t-Actin,Tn Ⅰ,Tn T,T-box and NK2.5 were also transcripted as detectd by RT-PCR.No positive results was found in control group.Conclusion HAFCDSC can form uniform EB-like structures after hanging drop culture for 5 days.HAFCDSC differentiate into cardiomyocyte-like cells through the form of EB-like structures after induction by 5-Aza.

Objective To observe the effects of acute hypoxia on the electrophysiological properties of vascular smooth muscle cells(VSMCs)of mesenteric artery in guinea pig.Methods A segment of mesenteric artery(MA)(outer diameter ＜ 100 μm)of guinea pig was digested with collagenase A and its adventitial connective tissue cleaned subsequently with fine tweezers.Whole-cell patch clamp recordings were performed to study the effects of acute hypoxia on the whole-cell membrane current,resting membrane potential(RP),membrane input capacitance(Cinput),and membrane input resistance(Rinput or its reciprocal membrane input conductance Ginput)of VSMC embedded in arteriolar segment.Results Acute hypoxia induced an outward current with an amplitude of(76 ± 23)pA at holding potential-40 mV and hyperpolarizated VSMC from a RP of(-22.5 ± 1.2)mV to(-42.0 ± 2.8)mV(P ＜ 0.01).Acute hypoxia increased the outward current of VSMC in a voltage-dependent manner.And this enhancement was more pronounced at potentials from 0 to + 40 mV.The whole-cell membrane current of VSMC induced by step commands(0,+ 20 and + 40 mY)increased from(140 ± 18)pA to(660 ± 124)pA(P ＜ 0.01),(282±23)pA to(1120 ±186)pA(P＜0.01)and(423 ±40)pA to(1800 ±275)pA(P＜0.01)respectively.In the presence of 1 mmol/L tetraethylammonium(TEA,a large conductance Ca2+-activated K+ channel blocker),the enhancement of VSMC membrane current by acute hypoxia was significantly reduced.Acute hypoxia increased the Rimput of VSMC in MA from(446 ±55)MΩ to(2187 ±290)MΩ(P＜0.01)and deereased the Cinput from(184.3 ±75.0)pF to(17.6 ±2.2)pF(P＜0.01).In the presence of 30 μmoL/L 18β-glycyrrhetinic acid(18βGA,a gap junction blocker)and 10 mmol/L TEA,the effects of acute hypoxia on the membrane current of VSMCs were almost abolished.Conclusion Acute hypoxia causes vascular hyperpolarization and vasodilation by activating large conductance Ca2+-activated K + channels of VSMC and inhibits gap junctions between VSMCs so as to improve microcirculation and localize hypoxia-induced damage.

Objective To establish a model of hematopoietic stem and progenitor cells with iron overload derived from umbilical cord blood(UCB)cells and explore the effects of reactive oxygen species (ROS)on the hematopoiesis of hematopoietic stem and progenitor cells with iron overload.Methods The model was established by adding different concentrations(50,100,200,400 μmol/L)of ferric citrate(FAC)into mononuclear cells from UCB and culturing for different times(6,12,24 h).The UCB cells were divided into 4 groups:control group,grup FAC,group FAC + N-acetyl-L-cysteine(NAC)and group FAC + L-Glutathione(GSH).Then the changes of ROS,labile iron pool(LIP),apeptosis,the capacity of hematopoietic clony forming(CFU-E,BFU-E,CFU-GM,CFU-mix)and the percentage and the numbers of CD34 +,CD33 +,GlyA+ cells were detected.And the changes of these indices were tested after the treatment of iron overload UCB with antioxidants(NAC and GSH).Results UCB cells were cultured with the addition of FAC at different concentrations for different times.The level of total ROS increased in time and concentration-dependent manners.The intracellular level of ROS peaked when cultured at 200 μ mol/L of FAC for 24 hours.Cells were treated with antioxidants NAC or GSH after cultured with 200 μmol/L FAC for 24 hours.Then the ROS levels of total cells,myeloid cells and erythroid cells decreased markedly versus normal controls.The LIP of total cells,myeloid cells and erythroid cells increased markedly when cells were cultured at 200 μmol/L of FAC for 24 hours versus normal controls(P ＜ 0.05).NAC and GSH had no effect on the level of LIP.The apoptotic rates of FAC-treated cells[(20.90 ± 3.45)％]increased significantly versus normal controls[(9.20 ± 1.29)％](P ＜ 0.05).The capacity of hematopoietic colony forming in FAC treated cells decreased markedly versus normal controls.The percentage and numbers of CD34 +,CD33 +,GlyA + cells of FAC-treated cells also decreased significantly versus normal controls(P ＜0.05).And these changes could be recovered by the addition of NAC or GSH.Conclusion Oxidative stress plays an important role in the injuries of hematopoiesis of hematopoietic stem and progenitor cells with iron overload by inducing the generation of ROS.These findings may help us find a specific target and improve the therapeutic efficacy of ineffective hematopoiesis in patients with iron overload.

Studies have shown that the use of zoledronic acid can reduce the recurrence of breast cancer in postmenopausal women.Researchers believe that this can be the key to deeply understand the mechanism of breast cancer recurrence,and provide a new option for patients'medical care.Zoledronic acid is a type of bisphosphonate,which is a group of drugs mainly used to treat osteoporosis.However, they are also used in cancer patients to prevent the effects of secondary bone tumors,such as pain and fragility of bones.Laboratory studies have shown that zoledronic acid may have direct anti-tumor effects and can enhance the effects of other chemotherapies,therefore, the multicenter AZURE trial led by Prof. Robert Coleman,located at Weston Park Hospital in Sheffield, UK,was conducted to further investigate.The trial enrolled 3360 patients with stage II/III breast cancer from 174 centers.They were randomly assigned to receive chemotherapy and/or endocrine therapy,with or without zoledronic acid.An interim analysis of the trial progress showed that, Patients did not see clinical therapeutic benefit. This indicates the lack of effectiveness of this drug, except for a group of women who had been menopausal for at least 5 years. The overall survival rate of this group of women was 85%, compared with the overall survival rate of 79% for women who did not receive zoledronic acid. This effect is independent of the disease characteristics shown by the stage of tumor development, estradiol receptor status and lymph node involvement. Prof. Coleman explains: "This is a small but meaningful increase. This finding is not enough to prove itself, but it is likely to change practice in terms of other studies and additional data expected to be available later this year".

A 46-year-old male was admitted to the hospital on September 28, 2008 due to "left limb mobility impairment for 1 month, and the lung was found to occupy space for 3 days". One month before admission, the patient showed involuntary shaking of the left limb without obvious trigger, intermittent attacks, and inflexible movements, which lasted for several minutes and could be relieved by itself. There was no dizziness, headache, nausea, vomiting and other discomfort, and no further examination was made. Two weeks ago, he suddenly fell to the ground after convulsions, unconscious and unable to respond to calls. After 20 minutes, he woke up, and after waking up, his left limb could not move. CT of the head in the emergency department of the local hospital showed a low-density shadow of the right frontal and parietal, considering cerebral infarction. After symptomatic treatment such as lowering intracranial pressure, improving microcirculation, activating blood circulation and removing stasis, the mobility of the lower limbs improved slightly. One week ago, MRI of the head enhanced showed multiple cranial masses, considering metastases (Figure 1). Positron emission computed tomography/computed tomography (PET/CT) showed a patchy hypermetabolic area of about 4 cm ×4 cm in the right upper lung, with standard uptake value (SUV) of 2.5, and a hypermetabolic nodule of about 2 cm ×2 cm in the left upper lung, SUV =3.3 Right lung cancer with brain metastasis was considered. He was admitted to our department after 2 times of cranial radiotherapy in the outpatient clinic of another hospital. He lost 2 kg in weight in the past month, had normal urine and defecation. He smoked 500 cigarettes per year and did not quit smoking. He denied the history of hypertension, diabetes, coronary heart disease, infectious diseases such as hepatitis and tuberculosis, blood transfusion, food and drug allergies, and traveling. Physical examination: conscious, body temperature 36.3℃, heart rate 70 beats/min, breathing 18 beats/min, blood pressure 110/70 mm Hg (1 mm Hg =0.133 kPa). Medium nutrition, conscious, a swollen lymph node about 1 cm ×2 cm in size can be palpable in the right axillary, hard in texture, without tenderness. The breathing sounds of both lungs were clear, and no dry or wet sounds were heard. No obvious abnormalities were found in the physical examination of heart and abdomen. The muscle strength of left upper limb was grade 3, left lower limb muscle strength was grade 4, right limb muscle strength was grade 5, and left Babinskin sign was positive. Laboratory examination: blood routine showed that the total number of white blood cells was 7.17×109/L, neutrophils were 73.5%, and hemoglobin was 13% Erythrocyte sedimentation rate 28 mm/1 h, CRP 45 mg/ml; Liver function showed lactate dehydrogenase 273 U/L; Renal function and electrolytes were normal; The coagulation function was normal. Chest enhanced CT showed round nodular shadows in the left upper lung, which seemed to be enhanced after enhancement, frosted glass-like density increased shadows in both upper lungs, and no enlarged lymph nodes in the mediastinum and hilum (Figure 2).

Since Weigle et al. first discovered the first Fox gene, namely FoxO1, FoxO3a, FoxO4 and FoxO6 in mammalian cells, there are 19 (A-S) subfamilies in Fox family [1-2], and FoxO (Forkhead box subtype O, FoxO) is one of the most deeply studied subfamilies. FoxO includes FoxO1, FoxO3a, FoxO4 and FoxO6 in mammalian cells. Although the members of FoxO have different degrees of similarity in molecular structure and physiological effects, the expression of each member in tissues is not uniform, which suggests that different FoxOs molecules have their own unique cellular functions. In recent years, it has been found that FoxO4 plays an important role in physiological regulation, metabolism, stress resistance, apoptosis and autophagy through transcriptional regulation and signal transduction pathway, and it has gradually become a hot spot in life science research.

The research of Human Papillomavirus (HPV) infection and the development of cervical cancer originated more than 30 years ago. Today, the scientific community has discovered and confirmed that HPV infection is more than 99% of the pathogens of cervical cancer [1]. HPV disrupts the protein regulation of host cells and causes chromosome instability, causes cellular gene mutation, and accumulates with time and then develops into cancer. The understanding and research of this process has laid the theoretical foundation for our understanding of the development of many other Human tumors [2].