OBJECTIVE: To investigate the efficacy of bone marrow mesenchymal stem cells (BMMSC) on children with refractory graft-versus-host disease (GVHD) and to judge the efficacy of BMMSC by dynamically monitoring the changes of cytokines in children with GVHD before and after infusion of BMMSC, so as to provide a theoretical basis for clarifying the mechanism of BMMSC. METHODS: 17 children with refractory aGVHD including 7 of grade II, 6 cases of grade III and 4 cases of grade IV after allo-HSCT were enrolled. All the children with aGVHD, who received routine immunosuppressive therapy, but the state of disease not improved, were treated with immunosuppressive drugs combined with BMMSC infusion. Study endpoints included safety of BMMSC infusion, response to BMMSC, and overall response of aGVHD. The serum levels of IL-2α, IL-6, IL-10, IL-8 and TNF-α in aGVHD patients were measured by chemiluminescence before infusion of BMMSCs and Day 7, Day 14 after infusion of BMMSCs. RESULTS: The cumulative median dose of BMMSCs was 5.5 (3.4-11.1) × 10/kg for average of 3.7 times, and the median time of 16.5 (4-95) days for the first infusion of MSCs. In 17 cases of refractory GVHD, 14 responded to treatment, whereas 3 patients failed. The total effective rate was 82.4% and no adverse reactions occurred. Of the 14 survived cases (82.4%), the median follow-up time was 944 (559-1245) days from the first infusion of MSCs. The levels of TNF-α in children with grade II, III and IV GVHD before treatment were 9.5±4.3 pg/ml, 16.3±10.9 pg/ml and 35.8±21.2 pg/ml respectively. The difference between grade II and IV, III and IV was statistically significant (P<0.05). Compared with the ineffective group of BMMSC infusion, the serum TNF-αlevel in the BMMSCs treatment effective group was 10.8±5.6 pg/ml vs 40.6±14.8 pg/ml (t=-3.901, P<0.05) before treatment. In the effective group of BMMSCs infusion, IL-10 20±17.4 pg/ml of day 14 was significantly higher than that 7.3±3.1 pg/ml before the treatment (t=-2.850, P<0.05), while , the serum levels of IL-2α, IL-6, IL-8, TNF-α were not statistically significantly different (P＞0.05). CONCLUSION The infusion of BMMSC is safe and effective in the treatment of refractory GVHD in children. TNF-αlevel relates with the severity of GVHD. BMMSC may play an anti-GVHD role by up regulating the level of cytokine IL-10 in vivo.

The purpose of this paper is to study the use rules of drugs for lung diseases in internal medicine department of Xin'an Wang's family, discuss the compatibility of common drugs for lung diseases, guide clinical application, and inherit Xin'an medicine. By retrospective study on lung diseases cases in Wang's internal medicine works, the lung diseases and use frequency of common drugs treated by Wang's medicine were counted, and the systematic clustering and association rule analysis of common drugs were conducted by using SPSS Statistic 20 and SPSS Modeler 18.0, respectively. The results showed that asthma, cold and cough were the main lung diseases treated by Wang's medicine, and the commonly used medicines included antitussive and antiasthmatic drugs, spleen-invigorating and dampness-removing drugs, and expectorants. The medicine taste was mainly bitter, pungent and sweet, with cold and warm properties in a balanced way, without severely cold or hot herbs, mainly attributing to the lung and stomach meridians. In clustering analysis, 10 drug combinations were obtained; association analysis showed that two, three, four association rules respectively had 11, 21, and 10 groups, and each drug group had 11, 16, and 5 items. Core combinations: Poria, Armeniacae Semen Amarum, Asteris Radix et Rhizome, Coicis Semen, Farfarae Flos, Dendrobii Caulis, Perilla Frutescens, Stemonae Radix, Citri Reticulatae Pericarpium, Cynanchi Stauntonii Rhizome et Radix, Meretricis Concha Cyclinae Concha, Belamcandae Rhizoma, and Pinelliae Rhizome. Xin'an Wang's medicine paid attention to the lung nature when treating lung diseases. Lung is a delicate organ, not resistant to coldness or heat, so severely cold or hot herbs shall not be used, and the clear and light drugs with functions of dispersing lung Qi, clearing phlegm evil, strengthening spleen, eliminating phlegm, and relieving cough and asthma are often used. Lung deficiency is a kind of deficiency of Qi and Yin, so both Qi and Yin shall be regulated. Deficiency of Yin would burn the lung and make the lung collaterals blocked. In this case, the lung collaterals shall be dredged for hemostasis. Long time of lung deficiency would hinder the distribution of body fluid, and lung shall be regulated to dissipate phlegm.
Data Mining ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Lung Diseases ; drug therapy ; Medicine, Chinese Traditional ; Meridians ; Retrospective Studies

OBJECTIVE: To investigate the effects of exosomes from human umbilical cord mesenchymal stem cells on the development of Treg and TH17 cells. METHODS: Exosomes from the serum-free-culture supernatants of hUC-MSC were harvested by ultracentrifugation. The electron microscopy, nanoparticle tracking analysis and western blot were used to identify the hUC-MSC-exosomes, such as the morphology, the paticle chameter, and the protein content. The PBMC stimulated with anti-CD3/CD28 were incubated with the exosomes for five days, and then the percentage changes of Treg and TH17 cells were analyzed by using flow cytometry. RESULTS: The hUC MSC-derived exosomes were saucer-like in morphology the averge diameter was approximately 142 nm. They were identified as positive for CD9 and CD63. Flow cytometry showed that the proportion of CD4CD25Foxp3 Treg cells in the PBMC were significantly higher, but the proportion of CD4IL17A T cells in the hUC-MSC-exosome group was obviously lower than that in the group without the hUC-MSC-exosom (control group) (P<0.05). CONCLUSION The hUC-MSC-exosomes have an immunomodulatory effect on T cells in vitro by increasing the ratio of Treg and reducing the ratio of TH17 cells, expecting the hUC-MSC-exosom as a novel cell-free target for immunotherapy.
Exosomes ; Humans ; Leukocytes, Mononuclear ; Mesenchymal Stem Cells ; T-Lymphocytes, Regulatory ; Th17 Cells ; Umbilical Cord

OBJECTIVE: To investigate the clinical characteristics, prevention and treatment of invasive fungal disease (IFD). METHODS: The clinical data of 164 patients who met the diagnostic criteria of IFD in our center from January 2012 to January 2015 were retrospectively analyzed. The incidence, clinical characteristics, related factors, treatment methods and prognosis were analyzed. RESULTS: Among 1289 cases of blood diseases, 164 cases suffered from IFD with inciduce of 12.7%. The main infection sites were as followed: lung, blood and gastrointestinal tract, with incidence of 84.2%, 5.5% and 3% respectively. The funge was found in 35 cases by detection; among fungi, the detected rate of candida albicans. aspergillus and candida glabrata was more high with 51.5%, 20% and 14.3% respectively. Among 164 childen with blood deseases complicated by IFD, 36 cases gained complete remission, 97 cases gained partial remission, 10 cases were stable, 11 cases were progressive and 10 cases died, the overall effective rate reached 81.1%. The univariate analysis showed that the gramulopenia, granulocyte recovery, long-term use of corticosteroid and immuno-suppressive agents, as well as different grades of diagnosis were significant factors affecting the efficacy of antifungal therapy for blood disease children with IFD, the multivariate analysis further showed that the granulocyte recovery and diagnosis grades were independent prognostic factors affecting the therapeutic efficacy for IFD children. The overall survival rate of IFD children with 12 weeks of antifungal treatnment was 81.7%, out of which the survival rate of IFD children at 12 weeks of treatment with itraconazole, voriconazole, amphotericin B and caspofungin was 81.4%, 80%, 69.4% and 97.1% respectively, there were significant differences in survival rate between each other by long rank test. In addition of caspofungin, the other 3 kinds of drugs had toxic side effects of different degrees, but IFD children could tolerated these effects after symptomatic treatment. CONCLUSION The incidence of IFD in children with blood deseases in our hospital is 12.7%, the lung is most common infective site, moreover patogens of IFD mainly is candida. The promotion of granulocyte recovery and early stratified diagnosis can contribule to the treatment of IFD. For the IFD children with better economic condition, the caspofungin is a potent antifungal agent with high efficacy, low toxicity and better prognosis.
Amphotericin B ; Antifungal Agents ; Child ; Hematologic Diseases ; etiology ; Humans ; Invasive Fungal Infections ; complications ; Retrospective Studies

Objective To investigate whether elevated baseline levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) are associated with an increased risk of breast cancer in Kailuan female cohort. Methods Females from Kailuan cohort (2006-2007) were included in this study. Information on check-up, hsCRP and NE were collected at baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) of association between baseline hsCRP and NE values and breast cancer risk. Results By December 31, 2015, a total of 18 866 participants were enrolled in this study. During the follow-up, 183 new cases of breast cancer were observed. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of breast cancer were 829/105, 1 211/105 and 1 495/105 in these 3 groups, respectively ( 2=12.08， P=0.002). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significantly increased risk of breast cancer (HR=1.71,95%CI: 1.18-2.47, P=0.005), howerver, we didn’t find the statistically significant association between NE level (<3.70×109/Lvs. ≥3.70×109/L) and the risk of brease cancer (P>0.05). Conclusions Elevated levels of hsCRP at baseline might increase the risk of breast cancer in females.

To analyze the effectiveness and safety of intermittent lung inflation combined with rigid ureteroscopy in the treatment of upper ureteral stones that were not fully visible. The clinical and imaging data of 56 patients with upper ureteral stone undergoing rigid ureteroscopic lithotripsy combined with intermittent lung inflation in Zhejiang Quhua Hospital from March 2016 to October 2017 were retrospectively analyzed.Intermittentt lung inflation was used to change and stabilize the position of ureteral calculi during the operation,so as to ensure the visual field of ureteroscopy.Holmium laser lithotripsy was performed to remove the stones.Urinary tract abdominal plain X-ray or CT urography was performed 1 and 3 months after the operation to evaluate the residual stones and the clinical efficacy. Stones were successfully removed after a single attempt in 48 patients.In 5 patients,stones escaped into the kidney during ureteroscopic lithotripsy,and thus flexible ureteroscopy were performed.In 3 patients,a second session of auxiliary procedure was required,among whom 2 patients received extracorporeal shock wave lithotripsy and 1 patient underwent extracorporeal shock wave lithotripsy+ureteroscopic lithotripsy.The stone-free rates 1 and 3 months after surgery were 94.6%(53/56)and 100%(56/56),respectively.No severe complication such as ureter perforation,gross hematuria,septic shock,or pneumothorax occurred during and after surgery. Intermittent lung inflation in tracheal intubation under general anesthesia in patients with proximal ureteral stones that can not be fully visible during rigid ureteroscopic lithotripsy was feasible and reliable.It can effectively change the location of stones and thus enable safe and effective lithotripy.It expands the indications of rigid ureteroscopy for treating upper ureteral stones.
Humans ; Lithotripsy, Laser ; Retrospective Studies ; Ureteral Calculi ; diagnostic imaging ; Ureteroscopes ; Ureteroscopy

Objective: To investigate the efficacy and safety of albumin-bound paclitaxel in the treatment of advanced malignant tumors. Methods: Patients in advanced stage of cancer who had had drug-resistant relapse after receiving multiple-line treatment received chemotherapy with albumin-bound paclitaxel from May 2016 to April 2018 in Daxing Hospital of Capital Medical University. Their clinical data were collected to evaluate the treatment efficacy and safety profile. Results: 36 patients who had advanced treatment-resistent tumors with evaluable data were enrolled. Of 36 patients, 55.56% (20) had previously received chemotherapy with paclitaxel. The objective response rate (ORR) was 8.33%, the disease control rate (DCR) was 25.0%, the median progression free survival (PFS) was 106 days, and the median overall survival (OS) was 183 days. The main adverse reactions of grade 3-4 were hematological toxicity, including neutropenia [36.11% (13/36)], anemia and thrombocytopenia [5.56% (2/36) and 16.67% (6/36)] in patients without neutropenia fever. Adverse effects of 3-4 degrees related to non-hematologic toxicity were not observed. Conclusions Chemotherapy regimen with albumin-bound paclitaxel has certain efficacy for advanced malignant tumors resistant to multiple lines of therapy and the adverse effects could be generally tolerated.

Background: Available research about the anatomic patterns of intertrochanteric fractures is lacking, and fracture mapping has not previously been performed on intertrochanteric fractures. This study aimed to determine the major trajectories of intertrochanteric fracture lines using computed tomography data from a series of surgically treated patients. Methods: In this study, 504 patients with intertrochanteric fractures were retrospectively analyzed. Fracture patterns were graded according to Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification. Fracture lines were transcribed onto proximal femoral templates and graphically superimposed to create a compilation of fracture maps that were subsequently divided into anterior, posterior, lateral, and medial fracture maps to create a three-dimensional (3D) pattern by reducing fragments in the 3D models. The fracture maps were then converted into frequency spectra. The major fracture patterns were assessed by focusing on the lateral femoral wall, lesser trochanter, intertrochanteric crest, and inner cortical buttress. Results: Anterior, posterior, lateral, and medial fracture maps were created. The majority of fracture lines (85.9%, 433/504) on the anterior maps were along the intertrochanteric line where the iliofemoral ligament was attached. In the medial plane, the majority of fracture lines (49.0%, 247/504) shown on the frequency spectrum included the turning point involving the third quadrant. In the posterior plane, the majority of fracture lines (52.0%, 262/504) involved the intertrochanteric crest from the greater to the lesser trochanter. In the lateral plane, the majority of fracture lines (62.7%, 316/504) involved the greater trochanter at the gluteus medius attachment. Conclusions The fracture patterns observed in the present study might be used to describe morphologic characteristics and aid with management strategies. Further classifications or modifications that incorporate the fracture patterns identified in this study may be used in future research.

BACKGROUND: In 1990, Wolff et al. reported that DNA was examined as a gene therapy tool, and emerged as a promising therapy after observations that simple injection of naked plasmid DNA and RNA led to profound transgene expression in vivo.DNA vaccines are recognized for harboring several distinguishing characteristics and advantages (including low cost, ease and rapidity of manufacturing, and stability) making them a method for addressing global health threats in the future. OBJECTIVE: To review the status and research progress of DNA vaccines in the view of mechanism of action: innate immune signaling from bacterial DNA, transfecting somatic cell by DNA vaccines, cross-presentation and cross-activation, transfecting antigen presenting cells by DNA vaccines, and apoptosis. METHODS: The first author retrieved the databases of PubMed and CNKI for the articles concerning DNA vaccines published between January 2000 and June 2017 using the keywords of "DNA vaccine, gene vaccine, plasmid DNA, cross-presentation, transfection, apoptosis"in English and Chinese, respectively. A total of 105 literatures were searched, and 47 eligible articles were included in accordance with the inclusion criteria. RESULTS AND CONCLUSION: The immunogenicity of DNA vaccines in humans has been limited by low expression levels of antigen, in comparison with the conventional protein vaccines in the past two decades. Studies on the mechanism of action of DNA vaccines in terms of antigen-presenting cell types able to cross-present DNA-encoded antigens, the activation of innate immune responses due to DNA itself and induction of cell apoptosis have suggested the opportunities to increase the immunogenicity of these vaccines.

BACKGROUND: Role of Wnt/β-catenin signaling pathway in the pathogenesis of osteoarthritis has been proved by numerous animal experiments and human specimen trials. Wnt/β-catenin signaling pathway and matrix metalloproteinase 13 (MMP-13) play important roles in pathological process of osteoarthritis, and they may be related with each other. OBJECTIVE: To detect the expression levels of β-catenin and MMP-13 in the synovial tissue of osteoarthritis, and to investigate the relationship between β-catenin and MMP-1 in the pathogenesis of osteoarthritis. METHODS: Synovial tissues were obtained from the 54 patients undergoing total knee arthroplasty or knee arthroscopic diagnosis and treatment surgery and 12 healthy patients suffering from amputation caused by trauma. The samples were divided into non-, mild-, medium-and severe-osteoarthritis groups based on advanced Mankin scores. The expression levels of β-catenin and MMP-13 in the synovial tissues were detected by immunohistochemistry, and correlation analysis was conducted. RESULTS AND CONCLUSION: Immunohistochemistry results showed that MMP-13 was negative in the non-osteoarthritis group, positive in 5 (50%) samples in the mild-osteoarthritis group, positive in 11 (65%) samples in the medium-osteoarthritis group and positive in 23 (85%) samples in the severe-osteoarthritis group. β-Catenin was positive in 1 (8%) sample in the non-osteoarthritis group, positive in 7 (70%) samples in the mild-osteoarthritis group, positive in 14 (82%) samples in the medium-osteoarthritis group and positive in 25 (93%) samples in the severe-osteoarthritis group. The expression levels of β-catenin and MMP-13 in the synovial tissues presented a positive correlation (r=0.806, P ＜ 0.001), and the levels increased with joint degeneration becoming severe. These results imply that there is a significant increase in the expression levels of β-catenin and MMP-13 in the synovial tissues of osteoarthritis compared with the non-osteoarthritis group, and β-catenin and MMP-13 exert effects in development of osteoarthritis. Beta-catenin and MMP-13 are closely associated with pathological changes such as cartilage degeneration and synovial inflammation, thus providing new theoretical direction and experimental basis for targeted gene therapy of osteoarthritis.