Objective:To establish and validate the prediction model for bone marrow metastasis (BMM) in malignant tumors by screening out laboratory multiparameters.Methods:This case-control study collected 444 cases of malignant tumor patients who were hospitalized in the First Hospital of Jilin University from March 2018 to March 2024, including 243 cases for model establishment set and 201 cases for model validation set. The model establishment set was divided into BMM positive group (81 cases) and BMM negative group (162 cases), and the model validation set was divided into positive group (67 cases) and a negative group (134 cases). We collected patients′ clinical information such as gender, age, clinical diagnosis, and results of 47 laboratory tests including routine blood analysis, coagulation, liver function, tumor markers, potassium, sodium, chloride, and calcium ion tests, bone marrow morphology, and bone marrow biopsy. BMM was taken as the outcome event, differencial variables were analyzed using inter group comparisons, the correlation among parameters was analyzed using Pearson correlation analysis, the risk factors for BMM were analyzed using multivariate conditional logistic regression analysis, to establish logistic model, followed by efficiency evaluation on BMM predictive model using receiver operating characteristic (ROC) curves.Results:In the model establishment set, Pearson correlation analysis of 28 parameters that differed between the BMM positive and negative groups revealed that the correlation coefficients of 17 parameters, including mean platelet volume (MPV), hematocrit (HCT), hemoglobin (HGB), and prothrombin time (PT), were no more than 0.6 ( P<0.05). Further multivariate conditional logistic regression analysis demonstrated that MPV, HGB, HCT, PT, red cell distribution width (RDW), platelet count (PLT), alkaline phosphatase (ALP), chloride (Cl -), and mean erythrocyte hemoglobin concentration (MCHC) were the risk factors of BMM occurence in malignancy [MPV ( OR=9.929, 95% CI 2.688-71.335), HCT ( OR=8.232, 95% CI 6.223-9.841), HGB ( OR=4.300, 95% CI 1.947-16.577), PT ( OR=3.738, 95% CI 1.359-11.666), RDW ( OR=1.995, 95% CI 1.275-3.807), ALP ( OR=1.025, 95% CI 1.012-1.045), PLT ( OR=1.014, 95% CI 1.002-1.031), MCHC ( OR=0.724, 95% CI 0.523-0.880) and Cl -( OR=0.703, 95% CI 0.472-0.967)]. In the model establishment set, combiation of risk factors provided an AUC of 0.943 (95% CI 0.898-0.987, P<0.001), a sensitivity of 86.3%, and a specificity of 89.2% for BMM prediction. In the model validation set, the AUC was 0.924 (95% CI 0.854-0.960, P<0.001), with a sensitivity and specificity of 86.7% and 83.8%, respectively. Conclusion:This study built and validated a multiple-parameter model for BMM, which may facilitate the timely detection of BMM and provide reference for decision making of bone marrow aspiration.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

Objective:To investigate the incidence of hypoalbuminemia in elderly patients undergoing endovascular treatment(EVT)for large vessel occlusion and to analyze the correlation between hypoalbuminemia and prognosis of EVT.Methods:A total of 640 elderly patients receiving EVT due to acute large vessel occlusion, aged(71.5±7.4)years with 377 males(58.9%), were enrolled into the prospective multicenter cohort study from July 2018 to May 2019.The patients were grouped as the low albumin group(serum albumin levels within 24 h after EVT <35 g/L, n=191, 29.8%)and as the normal albumin group(serum albumin levels≥35 g/L, n=449, 70.2%). The primary outcome was 90-day nerve functional independence defined by the modified Rankin Scale score 0-2.Outcomes were assessed as odds ratio( OR)by using multivariable logistic regression analysis. Results:The proportion of prognosis of good nerve functional independence at 90 d was lower in the low albumin group than in the normal albumin group[22.5%(43 cases) vs.41.9%(188 cases), OR=1.88, 95% CI: 1.20~2.95, P=0.01]. The incidence of early neurological deterioration was higher after treatment( OR=0.57, 95% CI: 0.37~0.88, P=0.01), and the proportions of multiple systemic complications were higher( P<0.01)in the low albumin group than in the normal albumin group. Conclusions:Hypoalbuminemia after EVT is correlated with the poor prognosis at 90 d in elderly patients.Elderly patients with hypoalbuminemia after EVT have higher incidences of multiple systemic complications.

Reform of public hospitals is key to the healthcare system reform.This article introduced how Hangzhou implemented such a reform of " Hangzhou characteristics" by referring to the hospital reform framework of the World Bank, and the theoretical achievements and practical experiences of domestic public hospitals′reform.Led by the service concept of " Medicine has its limitations but we have the courage to overcome, service is boundaryless and we must pursue excellence" , Hangzhou has established a public hospital value system of " reorientation to public welfare".The smart healthcare system serves as a focus, to support the delicacy management of the hospitals. The construction of hierarchical medical care system functions as the pillar, to support the coordinated development of hospitals, primary health institutions and public health institutions.This way a public hospital comprehensive reform mode is established featuring " one value system, 2 levels of organization structure, 6 mechanisms, and 19 supporting measures ". Its experiences may serve as reference to streamline hospital internal operation and external cooperation mechanism.

Objective To assess the treatment outcomes of anterior segment optical coherence tomography(OCT) assisted excimer laser phototherapeutic keratectomy (PTK) for fungal corneal ulcer.Methods Twenty-four patients (24 eyes) suffered from fungal corneal keratitis were collected by a retrospecive chart review with at least 6 months of follow-up data available.All corneal ulcer depth did not exceed 1/3 corneal thickness and were resistant to local and systemic medication therapy for at least 1 week.Patients were divided into 2 groups.14 patients with 14 eyes were taken PTK and 10 patients with 10 eyes were treated with lamellar keratectomy.Follow-up time was at least 6 months.Visual acuities,corneal thickness,confocal microscope,healing of the epithelial defect and inflammation and complications were recorded.Results The postoperative visual acuity in two groups were significantly improved,visual acuity of PTK treatment group improved significantly better than the control group (P ＜ 0.05).Healing time of PTK treatment group (19.43 ± 5.68) days was shorter than that of the control group (34.40 ± 5.38) days,the difference was statistically significant (P ＜0.05).There was no significant difference in the residual central corneal thickness between the PTK treatment group and the control group (P ＞ 0.05).Residual mycelium after operation in the treatment group was significantly decreased than that of control group.Healing time of epithelial in PTK treatment group (4.0 ± 1.1) days was shorter than that of the control group (6.20 ± 1.39) days,the difference was statistically significant (P ＜ 0.05).There was no corneal dilation in two groups.No recurrence in PTK treatment group was occurred.3 cases in control group had recurrence after 6 months,drug control was effective in 1 case,and other 2 cases undertook corneal transplantation.Conclusion Anterior segment OCT assisted PTK for corneal ulcer can effectively clear the lesion,accelerate epithelial healing,provide a new choice for the treatment of early superficial fungal corneal ulcer.

Objective By analysis of the key performance indexes of the clinical laboratory automation system, to clarify the advantage and optimize the comprehensive performance of the laboratory automation system.Methods Key performance indexes were Collected from January 2017 to April 2017 in biochemistry and immunoassay group of Clinical Laboratory of Shanghai Tong Ren Hospital.(1)The data were collected and compared by the before-and-after method,the starting time of the automation system and initial sample test were analyzed.(2)Key performance indexes were analyzed for the time of specimen registration,inspection,and reporting.(3)The specimen turnaround time(TAT)was analyzed based on two months operation of the laboratory automation system.In view of disadvantage of infectious assays, setting up priority sample absorption, then TAT performance was re-evaluated.(4)By the assessment of total serum dosage required in the automation system, the number of blood vacuum tubes were reduced reasonably.The pros and cons of laboratory automation system were analyzed and the potential improvement were proposed.Results (1)According to the sample peak shift forward,the system start time could move forward 30 minutes earlier.(2)With the adopting of railway logistics,the specimens were sent to the lab and the registration time was at 7:25 am,and the time required for specimen delivery was greatly reduced which made specimen test,report and audit time all moved forward accordingly.(3)Data has shown that specimen TAT declined dramatically based on the performance of the first two month operation of the automation system,biochemical items were shortened 2 h,and the immunoassay shortened 4 h,respectively.Moreover the trend keeps better gradually.With setting up priority absorption infectious tests,the TAT was improved greatly,TAT reduced the average by 40 min.(4)500 μl(including the sample in dead space of vacuum tube)were needed for all the 65 biochemical items included in the system, and 1 495 μl serum were used for the 28 immunoassay.As a result, a total of 2 000 μl serum will be enough for sample analysis by the system, which provided the feasibility to reduce 3 vacuum tubes averagely.Considering the current automation system does not include all the analysis items in our lab directory, a few tests remain to be performed on offline instruments respectively.The methodology for some infectious agents are different from previous method, therefore some test results may need a period of time for comprehensive clinical appreciation.Furthermore,due to the parallel connection of multiple instruments included in the system, more rigorous and frequent quality control becomes a necessity,which may rely on more strict quality control procedure to guarantee the quality.Conclusions The application of the automation system significantly enhanced the efficiency of clinical laboratory all round.In addition, by the quantitative indicators, it is possible to monitor the system operation performance real time, which may feedback and facilitate the improvement constantly,and result in auto confirmation the majority results,eventually.

Objective To investigate the efficacy of permanent left ventricular epicardial pacing through left lateral thoracotomy in children with complete atrioventricular block (CAVB)or complete left bundle branch block (CLBBB)as well as its effects on heart synchronization.Methods Permanent left ventricular epicardial pacemakers were implanted through left lateral thoracotomy in 26 children with CAVB or CLBBB in Heart Center,the First Affiliated Hospital of Tsinghua University.These children aged (2.3 ±2.1 )years old (1 month -9 years old),weight (1 1 .2 ± 5.8)kg (5 -32 kg),among them 1 5 cases were male and 1 1 cases were female.Among the 26 patients,24 patients had CAVB and 2 patients had dilated cardiomyopathy secondary to CLBBB.Fifteen children who visited the Pediatrics Department for acute upper respiratory tract infection were chosen as control group.The efficacy of left ventricular epi-cardial pacemakers was analyzed and its effects on heart synchronization were observed by using tissue Doppler imaging (TDI).Results Implantations of pacemakers were successfully conducted in all the 26 patients with no complications associated with operations.Left atrial and ventricular dual chamber epicardial pacemakers were implanted in 21 patients and left ventricular single chamber epicardial pacemakers were implanted in 5 patients.Within the follow -up period of (28.2 ±1 5.1 )months (1 month -51 months),atrial and ventricular leads were 1 00% effective.No significant diffe-rence was found in atrial electrode sensing,ventricular electrode threshold and ventricular electrode impedance com-pared with those during implantation(P >0.05).For the 6 patients with preoperative cardiac insufficiency,their left ventricular diastolic diameters decreased from (48.50 ±1 1 .1 0)mm to (40.67 ±6.40)mm after operation,and the difference was significant (t =2.96,P =0.030);but left ventricular ejection fraction increased from 0.27 ±0.08 to 0.53 ±0.08 after operation,and the difference was significant (t =-5.02,P =0.004).Two patients with right ven-tricular pacing developed pacemaker syndrome and were switched to left ventricular epicardial pacing.Their cardiac function returned to normal 1 .5 and 2.0 years later,respectively.Fifteen patients received evaluation of heart synchroni-zation by TDI.No significant difference was found in LVEF,septal -to -lateral wall motion delay,septal -to -posterior wall motion delay and standard deviation of Standard deviation of the peak tissue velocity between these 2 groups(all P >0.05).Conclusions For children requiring epicardial pacing,left ventricular epicardial pacing is safe and effec-tive,which can protect left ventricular systolic synchronization,prevent or reverse the pacemaker syndrome.

Objective To investigate the effect of rapid repeated cold air inhalation stimulation on cold-sensitive chan-nel transient receptor potential ankyrin 1(TRPA1) associated inflammatory cytokines in living lungs .Methods A total of 20 male Wistar rats were randomly and evenly divided into 4 groups:cold air inhalation group , warm air inhalation group , TRPA1 channel agonist inhalation group and normal group , respectively . Tracheal intubation was carried out after anesthesia in rats of cold air inhalation group , and the tubes were linked to the air temperature controlled device with the temperature controlled at ( 2 ±1 )℃.The rats of warm air inhalation group were treated in the same way as cold air inhalation group except for the temperature at (36 ±1)℃.The rats of both groups were treated for 3 times, 1 hour each time.There were 12 hour intervals between treatments .The rats of TRPA1 channel agonist inhalation group were treated with atomizing inhalation of 60 mmol/L acrolein at room temperature (24 ±2)℃for 3 times, 1 hour each time.There were 12 hour intervals between two treatments .The rats were sacrificed after the last treatment .The tracheas and left lung tissues of all rats were taken and total RNA was extracted .The mRNA expressions of TRPA1, interleukin 1 beta ( IL-1β), interleukin 5(IL-5),and neutrophil chemoattractant chemokine (CXCL-1/KC)in the rat lungs were detected by real-time quantitative PCR .Results TRPA1 was expressed in rat lung tissues .In the short term cold air inhalation group , the expressions of IL-1β,IL-5 and CXCL-1/KC mRNA in the rat lungs were higher than those of the warm air inhalation or the normal groups .Similar results were also found in the specific TRPA 1 channel positive agonist ( acrolein ) inhalation group . Conclusion In living animals, the TRPA1 channels of the lungs can be activated by short-term cold air(<17℃),which results in the increasing expression of some inflammatory cytokines in lungs .

Hepatitis B ; Humans ; Th17 Cells

Objective To construct the recombinant plasmid of protein CFP10-MPT48-TB8.4 of Mycobacterium tuberculosis and to investigate the diagnosis potential of this fusion protein in tuberculosis serodiagnosis.Methods The recombinant fusion protein CFP10-MPT48-TB8.4 was expressed, and identified by Western blot.The ELSIA based on the purified fusion protein was done,and used for screening in 230 cases of clinical serum samples including pulmonary tuberculosis patients ( n =150 ),pulmonary disease patients other than tuberculosis (n =70) and health controls (n =103 ).The test result was analyzed by Medcale11.5 software.Results The fusion protein CFP10-MPT48-TB8.4 was successfully expressed with a purity over 95％.Specific immunogenicity of the recombinant protein was confirmed by Western blot.The overall sensitivity and specificity obtained of ELISA were 56.7％ (85/150) and 90.8％ ( 157/173 ),respectively.The specificity was 85.7 ％ (60/70) in non-tuberculosis group and 94.2％ (97/103 ) in healthy group,respectively.Conclusion The recombinant protein of CFP10-MPT48-TB8.4 has a high sensitivity and specificity and may be a potential candidate antigen in tuberculosis serodiagnosis.