Objective:To analyze the clinical characteristics of invasive klebsiella pneumoniae liver abscess syndrome (IKPLAS), and compare it with common pyogenic liver abscess (CPLA). Methods:The social demography and clinical data of inpatients with pyogenic liver abscess from January 2011 to December 2021 in the Peking University People's Hospital were collected. Based on the presence or absence of invasive infections and the results of bacterial etiology, IKPLAS was diagnosed and compared with CPLA. The general information, symptoms, past medical history, auxiliary examinations and prognosis indicators of the two groups of patients were compared.Results:Total of 172 patients with pyogenic liver abscess were collected, including 25 cases of IKPLAS. Compared with CPLA group, the proportion of fever in IKPLAS group was lower, the proportion of diabetes history was higher, the proportion of monocytes was lower, and procalcitonin and urea nitrogen were higher(all P<0.05), the proportion of multiple abscesses is higher, and the positive rate of blood culture and the cultivation of klebsiella pneumoniae are both higher (all P<0.05).A total of 9 cases (5.2%) of patients developed septic shock, of which 2 cases (1.2%) died. The IKPLAS group had a higher proportion of ICU admissions ( P<0.05),but but the difference of mortality between the two groups was not statistically significant ( P>0.05). The most common sites of invasion infection in the IKPLAS group are the lungs(22/25), brain(9/25), and eyes(9/25). Conclusions:There are differences in clinical characteristics between IKPLAS and CPLA, the most common sites of invasion infection are the lungs, brain, and eyes, but there is no difference in mortality in this study. For PLA with pathogenic Klebsiella pneumoniae, it is necessary to carefully evaluate the presence of invasive lesions and provide targeted local treatment to better improve prognosis.

Objective:To investigate the clinical characteristics, risk stratification, thrombolytic effects and prognosis of 110 patients with acute pulmonary embolism (PE) treated with thrombolysis.Methods:The clinical data of 110 patients with PE admitted to Beijing University People's Hospital from May 2009 to March 2019 were retrospective analyzed. The clinical data including general information, symptoms and signs, blood pressure, artery blood gas, coaglulation, and radiography were collected. Inclusion criteria: high-risk and intermediate high-risk group. Exclusion criteria: intermediate low-risk and low-risk group. According to the prognosis and risk stratification, the patients were divided into survival group and non-survival group, high-risk group and intermediate high-risk group. The indicators above were compared between with χ 2 test, t test or nonparametric test where appropriate. Results:Of the 110 patients with PE, 49 patients were male and 61 female with an average age of 65±16 years old; and 12 patients were in the high-risk group and 98 in the intermediate high-risk group. The respiratory rate of the high-risk group was higher, and blood pressure, PO 2, SaO 2 before thrombolysis were more lower than the intermediate high-risk group ( P<0.05). One hundred and nine patients were treated with systemic recombinant tissue plasminogen activator (rtPA), 70 patients with 50 mg, and 39 patients with 100 mg. One patient, who was contraindicated to systemic thrombolysis (with active vagina bleeding), was treated with interventional local thrombolysis; another 5 patients treated with interventional local thrombolysis because the clinical symptom were not improved markedly. One hundred and two patients survived and 8 patients died, among which, 3 patients were in the high-risk group and 5 in the intermediate high-risk group. The age, heart rate, respiration rate of the non-survival group were higher than those in the survival group, and the PO 2 before thrombolysis, PCO 2 after thrombolysis were lower ( P<0.05). Bleeding complication were occurred in 22 patients: 18 patients with minor bleeding, such as bleeding gums, skin ecchymosis, and 4 patients with moderate-severe bleeding, such as cerebral hemorrhage, abdominal bleeding, gastrointestinal bleeding, and vagina bleeding. Thirteen of 70 patients in the 50 mg group and 9 of 39 patients in the 100 mg group occurred bleeding complication. The bleeding complication of the low dose group was lower than that of the standard dose group ( P<0.05). Conclusions:Thrombolysis is first-line therapy to high-risk PE. Thrombolysis is safe and effective in the intermediate high-risk group with a lower incidence rate of bleeding complication.

Objective:To explore the feasibility and optimization effect of modifying the Henry Ford Hospital (HFHS) RapidPlan model for stereotactic body radiation therapy planning based on local requirements.Methods:The following changes were made based on Henry Ford Health System(HFHS) Rapid Plan Lung SBRT model, taking the latest clinical guideline evidence and local clinical practice into account: Internal gross target volume(IGTV) and organ at risk(OAR) structure, lung, were added and set corresponding parameters.The upper value of planning target volume (PTV) was adjusted from 109% to 125%. The original training library was replaced with 73 local historical simultaneous integrated boosting plans, and statistical verification and outlier cleaning of the initial trained model were performed using Model Analytics software. Totally 10 cases not included in the model library were selected for independent verification, and automatic optimization result of the models before and after modifying were compared under the same beam condition. The following dosimetric parameters were compared after target dose normalization: conformal index (CI) of target volume, the mean doses, maximum doses and dose-volume parameters of OARs.Results:The " tail" of the PTV′s DVH and the " shoulder" and " tail" of the IGTV′s DVH of model M (local) validation plan (M (local)_P) performs higher than the original model HFHS (HFHS_P). The PTV_CI (1.07±0.13) of M local_P were significantly smaller than HFHS_P (1.25±0.24) ( Z=-2.497, P<0.05). Except for Heart_ D15 cm 3 and Heart_ Dmax, most of the M local_P dosimetric parameters of OARs were lower than HFHS_P, and the standard deviation was smaller. However, the difference of between two plans was no more than 3.06%. 10 HFHS_P plans don′t satisfy dose parameters requirement, two of which PTV_CI values are 1.52 and 1.74, far beyond the clinically acceptable range. Conclusions:Commercial model HFHS could be localized by replacing training library and adjusting parameters. Moreover, plans optimized by the modified model are local clinical acceptable in the aspects of target volume conformity and hotspots, and have a better performance in terms of OAR sparing and plan consistency.

Objective:To investigate the effects of ulinastatin on liver function in patients with liver cancer after major hepatectomy.Methods:The clinical data of 232 patients with major liver resection due to liver cancer were retrospectively analyzed. According to whether ulinastatin was applied after operation, patients were divided into treatment group (105 cases) and control group (127 cases). The postoperative inflammatory factors, liver function, postoperative complications and hospital stay were compared.Results:The levels of CRP、IL-6 and TBIL、ALT、AST were significantly lower than the control group 3 days after surgery (CRP: t=4.520, P=0.000; IL-6: t=17.982, P=0.000; TBIL: t=9.843, P=0.000; ALT: t=11.913, P=0.000; AST: t=4.520, P=0.000). The incidence of massive ascites in the treatment group (χ 2=4.212, P=0.040) and the average postoperative hospital stay ( t=9.994, P=0.000) were significantly lower than that in the control group. Conclusion:Early application of ulinastatin effectively inhibits the inflammatory process, protects liver function, reduces the incidence of massive ascites, and shortens the postoperative hospital stay.

Objective: To explore the treatment technique, occurrence and development patterns of such radiation injuries as in a major radiological accident in which a victim suffered mild bone marrow radiation sickness combined grade degree Ⅲ acute radiation induced skin injury, based on his dose estimation, clinical manifestations and disease treatments. Methods: History inquiry in detail, earlier physical dose estimation and biological dose estimation were conducted in conjunction with analyzing the chromosome aberration of peripheral blood lymphocytes. The physical dose was estimated by Monte Carlo method.The systematic laboratory and imaging examination was performed to evaluate the condition. The comprehensive analysis was conducted to determine the diagnosis and treatment plan. Results: At 3d after the exposure, "Ren" felt mild pain and discomfortable on the skin of the right index finger. The body of the right hand index finger was covered with blister at 21 d after exposure.The estimation of biological dose was 0.43 Gy (95%CI: 0.31-0.58 Gy), and the physical dose was estimated to be 36-164 Gy for each part of the right hand finger. The hematopoietic system, immune system and endocrine system were normal. The liver function index value was transiently increased. The liver damage resulted from the use of antibiotic-induced combined with the patient′s past medical history and admission examination result, and the relevant antibiotics were discontinued. The liver function returned to normal after liver protection treatment. At 22 d after irradiation, a right finger incision and decompression surgery were performed. The stem cells were extracted and implanted into the right index finger. After 59 days of hospitalization, there was no obvious discomfort in the body, and the right index finger recovered well, as well as the pain significantly relieved, and the knuckle activity was basically normal. Conclusions The patient with excessive radiation and grade Ⅲ acute radiation skin injury was successfully treated, and local application of autologous adipose-derived stem cell transplantation achieved good result .

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia resulting from decreased tubular phosphate reabsorption, with a low or inappropriately normal level of active vitamin D. The culprit tumors of TIO could produce fibroblast growth factor 23 which plays a role in regulating renal Pi handling and 25-hydroxyvitamin D 1α-hydroxylase activity. Chronic hypophosphatemia could eventually lead to inadequate bone mineralization, presenting as osteomalacia. The diagnosis should be considered when patients manifest as hypophosphatemia and osteomalacia, or rickets and needs to be differentiated from other disorders of phosphate metabolism, such as the inhereditary diseases like X-linked hypophosphataemic rickets, autosomal dominant hypophosphataemic rickets, autosomal recessive hypophosphataemic rickets and acquired diseases like vitamin D deficiency. Localization of responsible tumors could be rather difficult since the vast majority are very small and could be everywhere in the body. A combination of thorough physical examination, laboratory tests and imaging techniques should be applied and sometimes a venous sampling may come into handy. The technology of somatostatin-receptor functional scintigraphy markedly facilitates the localization of TIO tumor. Patients undergoing complete removal of the causative neoplasm generally have favorable prognoses while a few have been reported to suffer from recurrence and metastasis. For those undetectable or unresectable cases, phosphate supplements and active vitamin D should be administrated and curative intended radiotherapy or ablation is optional.
Calcification, Physiologic ; Diagnosis ; Fibroblast Growth Factors ; Humans ; Hypophosphatemia ; Metabolism ; Neoplasm Metastasis ; Osteomalacia ; Paraneoplastic Syndromes ; Physical Examination ; Prognosis ; Radionuclide Imaging ; Radiotherapy ; Recurrence ; Rickets ; Vitamin D ; Vitamin D Deficiency

Objective To investigate the effectiveness of T1 mapping on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA-enhanced) MRI for the assessment of liver function.Methods One hundred and twenty six patients with clinically suspected focal liver lesions and chronic viral hepatitis B underwent MRI were prospectively enrolled.Patients were divided into four subgroups as follows: chronic viral hepatitis B (n=22), liver cirrhosis with Child-Pugh A (n=52), Child-Pugh B(n=41),Child-Pugh C(n=11).Twenty three healthy volunteers with normal liver function were enrolled as control group.Non-enhanced and Gd-EOB-DTPA enhanced MRI of liver were performed in all subjects.Look-Locker sequences with exactly the same scan parameters and geometry position(the level of porta hepatis) were performed pre and post-contrast separately at 5, 10, 15 and 20 minutes after Gd-EOB-DTPA administration.T1 relaxation times and reduction rates of T1 relaxation times[ΔT1(%)]of the liver parenchyma were measured and calculated.One-way ANOVA was used to compare T1 relaxation times and ΔT1(%) for control group, chronic viral hepatitis B group, liver cirrhosis with Child-Pugh A group, Child-Pugh B group,and Child-Pugh C group.ROC curve analysis was performed to compare the diagnostic performance of T1 relaxation times and ΔT1(%) values in discriminating control group + chronic viral hepatitis B group + liver cirrhosis with Child-Pugh A group from Child-Pugh B + C group. Results T1 relaxation times and ΔT1(%)showed significant difference(P<0.05)among control group and different liver function groups. T1 relaxation times and ΔT1(%) of both liver cirrhosis with Child-Pugh B group and Child-Pugh C group were significantly different(P<0.05)in comparison with those of control group,chronic viral hepatitis B group and liver cirrhosis with Child-Pugh A group at all time points.T1 relaxation times of the control group,chronic viral hepatitis B group,liver cirrhosis with Child-Pugh A group and Child-Pugh B group reduced with the scanning time increase,ΔT1(%)raised with the scanning time increase.T1 relaxation times progressively increased from control group to Child-Pugh C group at every time point.ΔT1(%)showed a constant decrease from control group to Child-Pugh C group at all time points.The areas under ROC curve of T1 relaxation time pre and post-contrast at 5,10,15 and 20 minutes for assessment of liver function were 0.817,0.952,0.950,0.946,and 0.949 respectively.The areas under ROC curve of ΔT1(%)post-contrast at 5, 10, 15 and 20 minutes for evaluation of liver function were 0.873, 0.876, 0.885, and 0.898, respectively. Conclusion Gd-EOB-DTPA-enhanced T1 mapping MRI is useful for the evaluation of liver function, and helpful for distinguishing patients with moderate and severe liver damage from normal and mild liver damage.

Objective To evaluate the value of T1 mapping in Gd-EOB-DTPA-enhanced MRI for the assessment of liver function with HBV-related cirrhosis according to the model for end-stage liver disease (MELD) score.Methods 158 patients with HBV-related cirrhosis were included in this prospective study,and divided into MELD score ≤10 (n =103) group and MELD score ＞ 10 (n =55) group.All patients un derwent non-enhanced and Gd-EOB-DTPA enhanced MRI of liver,and T1 mapping was performed using Look-Locker sequences with the same scan parameters and geometry position (the level of porta hepatis) preand post-contrast at 5,10,15 and 20 minutes after Gd-EOB-DTPA administration.T1 relaxation times of the liver were measured and reduction rates of T1 relaxation times (△T1) were calculated.Independent samples t test was performed to compare T1 relaxation times and △T1 between MELD score≤ 10 and MELD score ＞ 10 groups.Receiver operating characteristic curve (ROC) analysis were done to differentiate the diagnostic performance of T1 relaxation times and △T1 between MELD score ≤ 10 and MELD score ＞ 10 groups.Pearson correlation analysis was used to analyse the correction between T1 relaxation times,△T1 and MELD scores.Results T1 relaxation times pre-and post-contrast at 5,10,15 and 20 minutes and △T1 post-contrast at 5,10,15 and 20 minutes of MELD score≤10 group were (889.3 ±91.2) ms,(377.5 ± 55.0) ms,(350.8±61.2)ms,(328.0±69.4)ms,(302.7±73.7)ms,(57.4±5.6)％,(60.4± 6.5) ％,(63.0 ± 7.3) ％ and (65.9 ± 7.8) ％,respectively,and those of MELD score ＞ 10 group were (936.6 ±95.4) ms,(460.2 ±68.5) ms,(457.5 ±94.5) ms,(453.4 ± 116.4) ms,(444.6 ± 134.6) ms,(50.8 ± 5.7) ％,(51.3 ± 7.9) ％,(51.8 ± 10.3) ％ and (52.8 ± 12.2) ％,respectively,and T1 relaxation times and △T1 at all time points were significantly different (P ＜ 0.05) between the two groups.The areas under ROC curve of T1 relaxation time pre-and post-contrast at 5,10,15,20 minutes and △T1 post-contrast at 5,10,15,20 minutes for differentiating MELD score ≤ 10 and MELD score ＞ 10 groups were 0.638,0.824,0.832,0.832,0.830 and 0.795,0.814,0.820,0.825,respectively.The correlation coefficients between T1 relaxation time pre-and post-contrast at 5,10,15,20 minutes,△T1 post-contrast at 5,10,15,20 minutes and MELD scores were 0.256,0.499,0.540,0.538,0.548,-0.412,-0.495,-0.507 and-0.527,respectively.Conclusions T1 mapping on Gd-EOB-DTPA-enhanced MRI is helpful for evaluating liver function with HBV-related cirrhosis.T1 relaxation times post-contrast on different time points were equally accurate as △T1.T1 relaxation times post-contrast and △T1 were superior to T1 relaxation times pre-contrast.

AIM:Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions .Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles ( MVs) from macrophages .METHODS:HMGB1 was added to the medium of macrophages , the secretion of MVs in the supernatant was tested by flow cytometry analysis .The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining .Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs .Then we subcutaneous injection into mice with MVs to induce regional minera-lization.RESULTS:HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis .TNAP activity, considered as a marker of MVs maturation , was higher in HMGB1-induced MVs compared to the control-MVs.HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model .Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization .Mechanistic experiments revealed that HMGB 1 activated neutral sphingomyelinase 2 ( nSMase2 ) that involved the receptor for advanced glycation end products ( RAGE ) and p38 MAPK (upstream of nSMase2).Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and min-eral deposition .CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part , via the RAGE/p38 MAPK/nSMase2 signaling pathway .Our findings thus reveal a novel mechanism by which HMGB 1 may participated in the early calcification of atherosclerotic plaques .