OBJECTIVE: To provide clinical basis for the diagnosis and treatment of chronic neutrophilic leukemia (CNL) and to provide possible molecular targets for the treatment. METHODS: By summarizing the clinical data of 14 patients with CNL, the clinical characteristics, gene mutation types and possible prognostic factors were analyzed. RESULTS: Among the 14 patients with CNL, males (9 cases) were more than females (5 cases), with a median age of 57 years old. The detection rate of CSF3R mutation was 92.86% (13/14), including 12 cases (85.71%) with T318I mutation and 1 case of Y799X mutation, and only 1 case was not detected for mutation of CSF3R. The ASXL1 mutation was detected in 42.86% (6/14) of the patients, all of which were nonsense mutations, including 4 cases with R693X and 2 cases with E705X, and 14.29% (2/14) of the patients was detected for SETBP1 mutation, all of which were with D868N mutation. No patients with simultaneous ASXL1 and SETBP1 mutations were found, and JAK2 and CALR mutations were not detected. All of the patients had normal karyotypes. These patients' median survival time was 30 months (95%CI 13.19-46.80), and the influence of age over 60 years old was statistically significant (21.83 months vs 35.35 months) (P＜0.05). CONCLUSION It is difficult to diagnose CNL. CSF3R T618I mutation is its specific mutation, and ASXL1 mutation and SETBP1 mutation have auxiliary diagnostic significance for CNL. The age＞60 years old at diagnosis is a factor of unfavourable prognosis.

BACKGROUND: Heterotopic ossification (HO) is a known complication of hip arthroscopy. We investigated incidence of HO after hip arthroscopy and determined whether revision for HO improved outcome. METHODS: A retrospective study was conducted on 242 patients (140 men and 102 women, mean age: 36.2 ± 9.5 years) who underwent hip arthroscopy for femoroacetabular impingement (FAI) between January 2016 and January 2018. The average follow-up period was 22.88 ± 11.74 months (range: 11-34 months). Thirteen (5.37%) cases of HO (six men and seven women, five left hips and eight right hips; mean age: 37.5 ± 4.7 years) were observed. Among them, four cases with HO with obvious pain symptoms and persistent non-remission underwent revision surgery to remove HO. Monthly follow-up was conducted. Visual analog scale (VAS), modified Harris Hip Score (mHHS), and non-Arthritis Hip Score (NAHS) were evaluated and compared between HO and non-HO patients. Independent sample t test, Mann-Whitney U test and the Chi-square test were used for inter-group comparisons. HO degree was evaluated using Brooker classification. Symptoms and function were evaluated before and after revision. RESULTS: A total of 242 patients were involved in this study. Thirteen cases (5.4%) had imaging evidence of HO. Nine (9/13) were classified as Brooker stage I, three (3/13) Brooker stage II, and one (1/13) Brooker stage III. HO was detected by ultrasonography as early as 3 weeks after operation. After primary surgery, the mHHS of the HO group and non-HO group increased by 13.00 (8.50, 25.50) and 24.00 (14.00, 34.50) points (Z = -1.80, P = 0.08), NAHS increased by 18.00 (9.50, 31.50) and 26.00 (13.50, 36.00) points (Z = -1.34, P = 0.18), and VAS decreased by 3.00 (2.00, 4.00) and 4.00 (3.00, 4.50) points (Z = -1.55, P = 0.12). Average follow-up time after revision was 9.00 ± 2.94 months; mHHS increased by 34.75 points (t = -55.23, P < 0.01) and NAHS by 28.75 points (t = -6.03, P < 0.01), and VAS decreased by 4 points (t = 9.80, P < 0.01). HO and non-HO patients were similar for demographic and surgical data, and clinical and functional scores. CONCLUSION HO incidence after arthroscopic treatment of FAI is similar to that found in previous studies. Most HO have no effect on clinical symptoms. Patients who undergo revision HO resection show improvement in pain and joint function.
Adult ; Arthroscopy ; adverse effects ; Female ; Femoracetabular Impingement ; surgery ; Hip Joint ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Ossification, Heterotopic ; diagnosis ; etiology ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: Ideal cardiovascular health (CVH) could predict a lower risk of developing cardiovascular diseases. This study was conducted to investigate the association between ideal CVH and subclinical atherosclerosis in a population cohort of Chinese adults aged ⪖ 40 years. METHODS: This study was designed as a cross-sectional analysis of 8,395 participants who had complete data at baseline and a prospective analysis of 4,879 participants who had complete data at 4.3 years of follow-up. Ideal CVH metrics were defined according to the American Heart Association. Subclinical atherosclerosis was evaluated by plaques in carotid arteries, carotid intima-media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), and urinary albumin-to-creatinine ratio (UACR). RESULTS: Both the prevalence and incidence of atherosclerosis measures were found to be decreased with increasing numbers of ideal CVH metrics at baseline (all P values for trend < 0.01). The levels of CIMT and UACR at follow-up showed an inverse and significant association with the numbers of ideal CVH metrics at baseline (both P values for trend < 0.05) but a borderline significant association with baPWV (P for trend = 0.0505). Taking participants with 0-1 ideal metric as reference, we found that participants with 5-6 ideal metrics had significantly lower risks of developing carotid plaques (odds ratio, OR = 0.46; 95% confidence interval, CI 0.27-0.79), increased CIMT (OR = 0.60; 95% CI 0.42-0.84), and increased baPWV (OR = 0.57; 95% CI 0.34-0.97) after full adjustments. A significant interactive effect of age and CVH was detected on CIMT and baPWV progression (both P values for interaction < 0.05). CONCLUSION The numbers of ideal CVH metrics showed a significant and inverse association with the risk of developing subclinical atherosclerosis in middle-aged and elderly Chinese adults, whereas its dose-response effect was attenuated in individuals aged ≥ 60 years and partially weakened in male participants.
Aged ; Atherosclerosis ; epidemiology ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Health Status ; Humans ; Male ; Middle Aged ; Prospective Studies

BACKGROUND: Primary pulmonary malignancies (PPMs) and non-pulmonary malignancies (PNPMs) may result in airway stenosis requiring stenting. This study aimed to compare and evaluate the clinical features and stent placement outcomes of airway stenosis caused by PPMs and PNPMs. METHODS: A total of 141 patients with malignant airway stenosis who underwent Micro-Tech stent placements between January 2004 and October 2017 at Department of Respiratory Medicine, Beijing Tian Tan Hospital, Capital Medical University were divided into PPM (n = 100) and PNPM groups (n = 41). Patients' clinical features and stent placement outcomes were collected and analyzed. Chi-square test was used to compare the categorical variables, while independent- or paired-sample t test was used to compare the continuous variables. RESULTS: There were no significant differences in age, sex, treatment history, respiratory symptoms, and incidence of obstructive pneumonia between groups. Multiple airway involvement (63.0% vs. 31.7%; χ = 11.459, P = 0.001) and atelectasis (17.0% vs. 2.4%; χ = 5.536, P = 0.019) were more common in the PPM group, while extraluminal obstruction (24.4% vs. 6.0%; χ = 8.033, P = 0.005) was more common in the PNPM group. Before stenting, the American Thoracic Society Dyspnea Index (ADI) and Karnofsky Performance Scale (KPS) scores showed no significant differences between groups (all P > 0.05). After stenting, a satisfactory rate of symptom improvement was achieved in both groups (98.0% and 100.0% in the PPM and PNPM groups, respectively; χ = 0.016, P = 0.898); ADI and KPS scores, which showed no significant differences between groups (all P > 0.05), were significantly improved in each group (all P < 0.001). Complications after stenting could be effectively managed using bronchoscopic procedures. CONCLUSIONS Among cases of malignant airway stenosis requiring stenting, those caused by PPM are more likely to involve multiple airways and are associated with atelectasis, while those caused by PNPM are more likely to cause extraluminal obstruction. Micro-Tech stent placement has the same immediate effect in terms of improvement in respiratory symptoms and performance status for both malignant airway stenosis caused by PPM and that caused by PNPM.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lung Neoplasms ; complications ; Male ; Middle Aged ; Stents ; adverse effects ; Tracheal Stenosis ; etiology ; therapy

We were interested in ascertaining differences in developmental neurotoxicity in normal and blood-stasis pregnant mice administered orally Rhizoma Curcumae and the underlying molecular biology mechanisms of any differences. To answer these questions, a blood stasis model was induced by being immersion in ice water. C57BL/6 mice with blood stasis, normal C57BL/6 mice, Nrf2 knock out (KO) mice with blood stasis were randomized into control groups and Rhizoma Curcumae exposure groups. The pregnant mice were administered Rhizoma Curcumae during pregnant day 5 to day 18. The neurodevelopment reflex was examined by the positive occurring time of avoidance precipice reflex tests. Measurement of glutathione (GSH) in brain of the offspring was performed by colorimetric assays. Transcription factor NF-E2-related factor 2 (Nrf2), glutamate cysteine ligase catalytic subunit (GCLc), and glutamate cysteine ligase modifier subunit (GCLm) mRNA and protein expression in brain of the offspring were examined by real-time RT-PCR and Western blot, respectively. All animal care and experiments procedures were reviewed and approved by the Animal Care and Use Committee of Qiqihar Medical College. Our results demonstrated for the first time evidence that C57BL/6 mice treated with Rhizoma Curcumae (10.0 g·kg^-1) extended the positive occurring time of avoidance precipice reflex tests of offspring mice compared with the normal control group (P<0.05). We could not find any significant change in that of blood-stasis pregnant mice offspring compared with the normal control group (P>0.05). Compared with the normal control group, level of glutathione, mRNA and protein expression of Nrf2, GCLc, and GCLm significantly increased in brain of the offspring of blood-stasis pregnant mice (all P<0.05). However, mice treated with Rhizoma Curcumae (10.0 g·kg^-1) did not change those of offspring (all P>0.05). Knock out Nrf2 using CRISPR/Cas9 extended the positive occurring time of avoidance precipice reflex tests of offspring of blood-stasis pregnant mice (P<0.05). To conclude, developmental neurotoxicity of the blood-stasis pregnant mice to Rhizoma Curcumae was weaker than that of the normal pregnant mice. Cold-induced Nrf2 activation has important roles in "YOU-GU-WU-YUN" phenomenon of Rhizoma Curcumae.

BACKGROUND: Cell-free stem cell therapy has been an issue of concern, but there is no conclusion on how to extract high-quality exosomes. OBJECTIVE: To extract exosomes from human umbilical cord mesenchymal stem cells by using three different methods, and then to screen the optimal method. METHODS: Exosomes were extracted from human umbilical cord mesenchymal stem cells by using the Total Exosome Isolation test kit, Exo Quick test kit and differential ultracentrifugation method, respectively. Then, transmission electron microscopy was used for morphological observations, BCA was utilized to quantify the protein, and western blot assay was applied to detect surface markers CD9, CD81 and CD63. RESULTS AND CONCLUSION: Extraction of exosomes was completed by all the three methods, and round or oval membranous vesicles were observed under the transmission electron microscope. The protein content and purity of exosomes was highest in the differential ultracentrifugation group, followed by the Exobiology Quick kit group, and lowest in the Total Exosome Isolation kit group, and there were significant differences among the three groups (P < 0.05). Under the same protein concentration, surface specific markers, CD81, CD63 and CD9, were expressed highest in the differential ultracentrifugation group, followed by the Exobiology Quick kit group, and lowest in the Total Exosome Isolation kit group. The operating time was significantly lower in the Exobiology Quick kit group compared with the other two groups (P < 0.05). To conclude, despite a longer operating time, the differential ultracentrifugation method is a rational method to extract enough exosomes with relative high purity.

OBJECTIVETo investigate the effect of Statins on proliferation and apoptosis in human acute T lymphocytic leukemia (T-ALL) cells and its possible mechanism.

METHODSJurkat and CCRF-CEM cells were cultured in different concentrations of Fluvastatin and Simvastatin for 24 h respectively. Then, the cell growth inhibition level was defected by CCK-8; the DNA replication was analyzed by EdU; the cell apoptosis was analyzed by Annexin V/7-AAD double labeling; the cell cycle changes were analyzed by flow cytometry; the expressions of Cyclin D1, p21, p27, BAX, BCL-2 and p-Akt were determined by Western blot.

RESULTSFluvastatin and Simvastatin both significantly inhibited the growth of Jurkat and CCRF-CEM cells in a dose-dependent manner. The inhibitory rate of Jurkat and CCRF-CEM cells at 0.2 mmol/L Fluvastatin was 41.14% and 57.08% respectively, while the 0.2 mmol/L Simvastatin could supress 68.42% of Jurkat and 77.10% of CCRF-CEM cells. Half or more than half of cell inhibition were observed in Statins-treated groups with significantly statistical differences, compared with the control groups (P<0.05). After the Jurkat and CCRF-CEM cells were treated with Fluvastation and Simvastation of different concentrations for 24 hours, the proportion of early and later apoptotic cells both increased; moreover, the total apoptotic rate increased significantly(P<0.05) at 0.2 mmol/L and 0.3 mmol/L concentration of Fluvastatin and Simvastatin. The detection of cell cycle showed that both of Jurkat and CCRF-CEM cells were arrested in G phase. Western blot revealed that, in comparison with the control group, the expressions of BAX, p21 and p27 in cells treated with Statins were up-regulated, while Cyclin D1, BCL-2 and p-Akt expressions were down-regulated.

CONCLUSIONStatins can suppress T-ALL cell proliferation and induce cell apoptosis through the inhibition of Akt pathway.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Proto-Oncogene Proteins c-akt ; Signal Transduction

The HA gene of H9N2 influenza virus (A/chicken/Hunan/04.14 (H9N2)) was amplified and sequenced. The RNA was synthesized by in vitro transcription. The RNA transcription solutions were diluted to 10⁹ copies/μL using the RNA storage solution. The aliquoted RNA solutions were used to evaluate the homogeneity and stability. The results were determined by the average value obtained from four independent laboratories. Furthermore, the fluorescence quantitative RT-PCR method was also developed to verify the detection accuracy of clinical samples. The detection limit of this method is approximately 10 copies. Taken together, the RNA transcription solution established in our study can used as positive standard reference for rapid detection of H9N2 influenza virus.

OBJECTIVETo investigate clinical effect of transverse tibial bone transport micro vessels regeneration technology combined with vacuum drainage in treating diabetic foot ulcer.

METHODSFrom November 2015 and December 2016, clinical data of 19 diabetic foot ulcer patients treated with transverse tibial bone transport micro vessels regeneration technology combined with vacuum drainage were retrospective analyzed, including 15 males and 4 females aged from 42 to 82 years old with an average of (64.57±7.14) years old;the courses of diabetic ranged was (14.62±6.19) years;12 cases on the left side and 7 cases on the right side;the area of ulcer ranged from 2 cm×3 cm to 8 cm×6 cm. All patients were stage D according to Texas classification, 3 cases were grade 2, 10 cases were grade 3 and 6 cases were grade 4. Ankle-brachial index and Michigan Neuropathy Screening Instrument (MNSI) were used to evaluate recovery of peripheral vessel and nerve before and after operation, the result of angiography and vascular ultrasound were also compared after operation.

RESULTSSeventeen of 19 patients were followed up from 3 to 13 months with an average of 6.9 months. Seventeen patients' surface wound were healed. Ankle-brachial index was increased from (0.51±0.20) before operation to (0.93±0.18) at 3 months after operation, and had significant difference(=13.63, =0.000);MNSI was increased from (4.06±1.36) before operation to(5.76±1.44) at 3 months after operation, and differences were statistically significant (=7.31, =0.000). Postoperative angiography and vascular ultrasound showed satisfied regeneration of micro-vessel and affected foot achieved normal movement and daily life.

CONCLUSIONSTransverse tibial bone transport micro vessels regeneration technology could reconstruct micro-vessel under lower affected limb, promote recovery of peripheral vessel and nerve, while with vacuum drainage could promote wound healing, has advantages of simple operation, obvious clinical effect, and high success rate of limb-salvage, and is one of ideal treatment for diabetic foot ulcer.

Adult ; Aged ; Aged, 80 and over ; Angiography ; Ankle Brachial Index ; Diabetic Foot ; surgery ; Drainage ; Female ; Humans ; Male ; Middle Aged ; Regeneration ; Retrospective Studies ; Tibia ; blood supply ; Treatment Outcome ; Ultrasonography ; Vacuum

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage