Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

Objective: To analyze the short-term effect of individual atmospheric PM_2.5 exposure on the diversity, enterotype, and community structure of gut microbiome in healthy elderly people in Jinan, Shandong province. Methods: The present panel study recruited 76 healthy elderly people aged 60-69 years old in Dianliu Street, Lixia District, Jinan, Shandong Province, and followed them up five times from September 2018 to January 2019. The relevant information was collected by questionnaire, physical examination, precise monitoring of individual PM_2.5 exposure, fecal sample collection and gut microbiome 16S rDNA sequencing. The Dirichlet multinomial mixtures (DMM) model was used to analyze the enterotype. Linear mixed effect model and generalized linear mixed effect model were used to analyze the effect of PM_2.5 exposure on gut microbiome α diversity indices (Shannon, Simpson, Chao1, and ACE indices), enterotype and abundance of core species. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 352 person-visits. The age of 76 subjects was (65.0±2.8) years old with BMI (25.0±2.4) kg/m². There were 38 males accounting for 50% of the subjects. People with an educational level of primary school or below accounted for 10.5% of the 76 subjects, and those with secondary school and junior college or above accounting for 71.1% and 18.4%. The individual PM_2.5 exposure concentration of 76 subjects during the study period was (58.7±53.7) μg/m³. DMM model showed that the subjects could be divided into four enterotypes, which were mainly driven by Bacteroides, Faecalibacterium, Lachnospiraceae, Prevotellaceae, and Ruminococcaceae. Linear mixed effects model showed that different lag periods of PM_2.5 exposure were significantly associated with a lower gut α diversity index (FDR<0.05 after correction). Further analysis showed that PM_2.5 exposure was significantly associated with changes in the abundances of Firmicutes (Megamonas, Blautia, Streptococcus, etc.) and Bacteroidetes (Alistipes) (FDR<0.05 after correction). Conclusion: Short-term PM_2.5 exposure is significantly associated with a decrease in gut microbiome diversity and changes in the abundance of several species of Firmicutes and Bacteroidetes in the elderly. It is necessary to further explore the underlying mechanisms between PM_2.5 exposure and the gut microbiome, so as to provide a scientific basis for promoting the intestinal health of the elderly.
Aged ; Humans ; Male ; Middle Aged ; Feces/microbiology* ; Gastrointestinal Microbiome ; Particulate Matter ; RNA, Ribosomal, 16S/genetics* ; Female

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214⁺AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214⁺AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214⁺AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214⁺AL. Disease recurrence is the most important factor affecting long-term survival.
Male ; Female ; Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/methods* ; Leukemia, Myeloid, Acute/therapy* ; Survival Analysis ; Remission Induction ; Acute Disease ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Recurrence ; Nuclear Pore Complex Proteins

Humans ; Aged ; Hip Fractures/surgery* ; Treatment Outcome

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Betacoronavirus ; Consensus ; Coronavirus Infections ; complications ; epidemiology ; prevention & control ; Epidemics ; Humans ; Minimally Invasive Surgical Procedures ; Musculoskeletal Diseases ; complications ; therapy ; Pandemics ; prevention & control ; Pneumonia, Viral ; complications ; epidemiology ; prevention & control

BACKGROUND: The reverse obliquity inter-trochanteric fracture is a distinct fracture pattern that is mechanically different from most inter-trochanteric fractures and the optional treatment of it is still controversial. The purpose of this study was to compare differences in the efficacy of a novel nail (medial support nail [MSN-II]) and proximal femoral nail anti-rotation (PFNA-II) in the treatment of reverse obliquity inter-trochanteric fractures (Arbeitsgemeinschaft fur Osteosynthesfrogen/Orthopedic Trauma Association [AO/OTA] 31-A3.1) using finite-element analysis. METHODS: Modeling software was used to establish a three-dimensional model of MSN-II and PFNA-II and an A3.1 inter-trochanteric fracture model. Abaqus software was used to implement different force loads to compare finite-element biomechanical parameters such as the maximum stress in implant and the displacement of fracture site. RESULTS: The femoral stress, implant stress and fracture site displacement of MSN-II was less than that of PFNA-II. The results indicated that the maximal femoral stress was 581 MPa for PFNA-II and 443 MPa for the MSN-II. The maximum stress values in the PFNA-II and MSN-II models were 291 and 241 MPa, respectively. The maximal displacements of the fracture site were 1.47 and 1.16 mm in the PFNA-II and MSN-II models, respectively. CONCLUSION Compared with PFNA-II for inter-trochanteric fracture (AO/OTA 31-A3.1), MSN-II which was designed with a triangular stability structure can provide better biomechanical stability. The MSN-II may be a feasible option for the treatment of reverse obliquity inter-trochanteric fracture.
Bone Nails ; Femur ; Finite Element Analysis ; Fracture Fixation, Intramedullary ; Hip Fractures/surgery* ; Humans ; Treatment Outcome

OBJECTIVE: A3 intertrochanteric fracture is an extremely unstable fracture, which is often treated with intramedullary nail, but the implant failure is common due to the posterior medial fragment cannot be reconstructed. A new medial sustainable nail (MSN-Ⅱ) which can reconstruct the femoral medial support by sustainable screw was introduced in this study. The mechanical effect was verified by biomechanical experiment. METHODS: The loss medial support model of intertrochanteric fracture (A3) was made by artificial Sawbones model, fixed with MSN-Ⅱ and PFNA-Ⅱ, underwent axial loading and axial failure tests. The axial stiffness, yield load, displacement of head-neck fragment and torsional angle of fracture site of these nails were recorded and compared for biomechanical differences. The effect of early reconstruction of medial support with MSN-Ⅱ was determined. RESULTS: The axial stiffness, yield load, the displacement of head and neck fragment when the axial load was 1 800 N and torsional angle of the fracture site after the axial failure test of MSN-Ⅱ were (222.76 ±62.46) N /mm, (4 241.71 ±847.42) N, (11.51 ±0.62) mm, (1.71 ±0.10)° respectively, while the PFNA -Ⅱ was (184.58±40.59) N /mm, (3 058.76±379.63) N, (16.15±1.36) mm, (2.52±0.26)°respectively. The difference between the two groups was statistically significant. CONCLUSION The axial stiffness of MSN-Ⅱ is better than that of PFNA-Ⅱ. The MSN-Ⅱ can bear more loads when fixed A3.3 intertrochanteric fracture and has greater axial and rotational stability. It is an effective means to reconstruct the medial support of A3 intertrochanteric fracture.
Biomechanical Phenomena ; Bone Nails ; Bone Screws ; Femur ; Fracture Fixation, Intramedullary ; Hip Fractures/surgery* ; Humans

Objective:To explore the method and curative effect evaluation of repairing and rebuilding the long segmental bone defect after resection of long bone malignant tumors in adolescents.Methods:Reviewed our experience in 10 patients. Among them, 4 were male and 6 were female. The age was 10.2 years old (range, 6-16 years old). Including 7 cases of osteosarcoma, 3 cases of Ewing's sarcoma; 2 cases of humerus tumors, 7 cases of femoral tumors, and 1 case of tibial tumors-who presented between April 2015 and October 2019, in which the proportion of bone defect account for 71.4%-89.3% of the total length of diseased bone after tumor resection, with an average value of 80.9%. Considering the epiphyseal growth of young people, on the premise of ensuring enlarged tumor resection, we use traditional fibula autograft and prosthesis combined with steel plate, 3D printing design to retain the super-prosthesis of the epiphysis, and 3D printing bone trabecular was processed for the sake of making it grow successfully into the binding part of prosthesis and bone as we expect, simultaneously, the design of the short-force arm retaining the bilateral epiphysis can assit the steel plate and interlocking screws to enhance the stability.Results:The operation was completed successfully, and there were no complications such as nerve and blood vessel injury during the operation. After follow-up of 4-8 months, with an average follow-up of 22.9 months. One patient's review of X-ray film after 2 years of the operation showed that the transplanted fibula had a sign of bone resorption, and the internal fixation was in it's original position without obvious abnormalities. Two cases' auxiliary steel plates had fractured within one and a half to two years after surgery. With replacing the fractured steel plates, the internal fixation was good until now. According to the evaluation standards of the International Society of Limb Salvation: 2 cases of humerus osteosarcoma were respectively scored 23 points, 26 points, an average of 24.5 points; 4 cases of femoral osteosarcoma and 3 cases of femoral Ewing's sarcoma respectively scored 26 points and 25 points, 19 points, 30 points, 27 points, 24 points, 28 points (average, 25.6 points); 1 case of tibial osteosarcoma scored 26 points; all obtained relative satisfying treatment results.Conclusion:The combination of 3D printing and traditional machining techniques to produce an individualized long segmental prosthesis that preserves the epiphysis which applicated in the limb salvage treatment of bone malignant tumors can achieve excellent therapeutic effect.

Purpose: Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. Materials and Methods: We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. Results: Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. Conclusion RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.