[Treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations].

Objective: To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations. Methods: This is a retrospective case series. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children's Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged (M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results: There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection (Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 patient in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn't have obvious respiratory symptoms. Conclusions: The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.

[Surgical treatment strategy of pulmonary artery sling: a series of 110 cases].

Objective: To examine the effect of surgical treatment in children with pulmonary artery sling and the surgical treatment strategy. Methods: Relevant data of 110 children with pulmonary artery sling admitted to the Department of Cardiac Surgery, Children's Hospital Affiliated to Shandong University from February 2017 to July 2022 were retrospectively analyzed. There were 55 males and 55 females, aging (M(IQR)) 9.0 (10.6) months (range: 1 to 96 months). The weight was 7.8 (3.5) kg (range: 2.5 to 25.0 kg). Of the 110 patients, 108 had different degrees of tracheal stenosis and 2 had normal trachea. Left pulmonary artery transplantation and tracheoplasty were performed in 78 patients. Left pulmonary artery transplantation was performed in 30 patients (11 in our hospital and 19 in other hospitals) due to the lack of an early tracheoplasty technique, in which 24 patients needed stage Ⅱ tracheoplasty due to obvious respiratory symptoms and limited activity endurance, and 6 cases did not intervene. Two children with normal trachea only underwent left pulmonary artery transplantation. Results: Among the 78 children who underwent surgery in the same period, 70 cases recovered smoothly after surgery, of whom respiratory symptoms were significantly reduced or disappeared during the 1 to 65 months follow-up, with similar activity endurance to normal children of the same age. Eight cases died, including 4 cases of postoperative multi-drug resistant bacteria infection, died from tracheal anastomotic opening or septic shock, 1 cases with severe congenital heart disease died from postoperative low cardiac output syndrome difficult to correct, 1 case died from blood pressure could not be maintained due to the compressed left pulmonary artery after transplantation, 2 cases of postoperative digestive system diseases (adhesive intestinal obstruction, gastrointestinal bleeding, etc.). The 24 patients in the staging group were followed for 1 to 84 months. All patients needed stage Ⅱ tracheoplasty due to respiratory symptoms and decreased endurance to activity. Eight cases of the non-intervention tracheal group were successfully separated from the ventilator, cured and discharged in a short period of time. Conclusions: Most children with pulmonary artery sling have tracheal stenosis. Children with low degree of tracheal stenosis and inconspicuous respiratory symptoms can only undergo left pulmonary artery transplantation by lateral thoracotomy. For patients combined with severe tracheal stenosis or obvious respiratory symptoms, a simultaneous left pulmonary artery transplantat and tracheoplasty is recommended.

[Surgical tracheoplasty for children with congenital tracheal stenosis undergoing previous balloon dilatation or tracheal metal stent placement: a series of 9 cases].

Objective: To examine the outcomes of Slide tracheoplasty for the children with severe congenital tracheal stenosis received previous repeated balloon dilatation or metal stent placement under endoscopy. Methods: A retrospective study was conducted in 9 children with congenital tracheal stenosis undergoing previous interventional therapy under tracheoscopy and later received Slide tracheoplasty due to obvious respiratory symptoms at Department of Cardiac Surgery, Qilu Children's Hospital of Shandong University between February 2017 and July 2021. There were 7 males and 2 females with a median age at operation of 72.4 months (range: 13.3 to 98.9 months), and the median weight was 19.0 kg (range: 9.0 to 33.0 kg). Among the 9 patients, 2 patients began to receive repeated balloon dilatation (more than 3 times) 17.8 and 51.8 months ago respectively. One patient received metal stents placement into the trachea for 4 days and the other 6 children for median 56.8 months (range: 21.6 to 74.2 months). Complete tracheal cartilage rings and long segmental stenosis were present. in all 9 children. Operative details and outcome measures, including the need for endoscopic airway intervention and mortality, were collected. Results: Slide tracheoplasty was performed in all cases. Two patients with repeated balloon dilatation had different thickness of tracheal wall, local scar hyperplasia and irregular lumen. Among them, 1 case had obvious local calcification of tracheal wall, which was difficult to suture. The metal stent in one patient with short time of placement was completely removed. However, only part of the metal stents could be removed due to the long placement time in the other 6 cases. There was no operative death in the 9 children. The median postoperative tracheal intubation time was 25.3 hours (range: 17.4 to 74.5 hours). A silicone stent was placed in the trachea of 1 child due to obvious respiratory symptoms. Follow-up of median 11 months (range: 1 to 23 months) showed that no death occurred after discharge and all children had basically normal activity tolerance with no obvious respiratory symptoms. Conclusions: Slide tracheoplasty is feasible for children undergoing prior balloon dilatation or metal stents placement. Previously repeated balloon dilatation or metal stent placement under endoscopy increased the difficulty of slide tracheoplasty, the metal stent could not be completely removed after a long time.

[A case-control study of multiple myeloma patients with central nervous system involvement].

Objective: To investigate the treatment options for multiple myeloma patients with central nervous system involvement (CNS-MM) , as well as their clinical characteristics and prognostic factors. Methods: Between January 2011 and January 2022 our center diagnosed 18 people with CNS-MM. A retrospective analysis was done on the clinical information from the initial diagnosis and central nervous system involvement, and it was compared to 1∶3 matched newly diagnosed MM from the same period. Analysis was done on the clinical characteristics and survival rates of the two groups. Results: In patients with CNS-MM, the median time of onset was 14.2 (0.9-79.6) months and the median overall survival (OS) was 30.5 months from initial diagnosis and only 3.8 months in patients after CNS involvement. The CNS-MM patients showed more IgD type (P=0.010) , severer anemia (P=0.014) , a higher proportion of bone marrow plasma cells (P=0.013) , more extramedullary lesions (P=0.001) , and increased lactic dehydrogenase (LDH) (P=0.009) when compared to the control group. Lenalidomide or pomalidomide-based combinations had higher rates of hematology and CNS remission than bortezomib or daratumumab-based regimens (75.0% vs 16.7% , P=0.019) . Patients who received IMiD-based regimens and had 2 high-risk factors at initial diagnosis (high LDH and extramedullary lesions) had a significantly lower incidence of CNS-MM (P=0.026) . At the initial diagnosis, LDH (P=0.008, HR=7.319, 95% CI 1.663-32.219) and extramedullary lesions (P=0.006, HR=8.054, 95% CI 1.828-35.486) were independent risk factors for the occurrence of CNS-MM. Conclusion: Patients with CNS-MM had a poor prognosis. Patients with high LDH or extramedullary lesions at the time of the initial diagnosis are more likely to have CNS-MM. The prognosis of this patient may be improved by immunoregulator-based therapy.

Cartilaginous endplate avulsion is associated with modic changes and endplate defects, and residual back and leg pain following lumbar discectomy.

OBJECTIVE: While cartilaginous endplate (CEP) avulsion is a common finding in discectomy due to lumbar disc herniation, its roles in residual back and leg pain, associations with Modic changes (MCs) and endplate defects (EPD) remain unknown. DESIGN: Patients with a single-level lumbar disc herniation who underwent endoscopic discectomy were studied. On MR images, the adjacent endplates of the herniated disc were assessed for MCs and EPD. The presence of CEP avulsion was examined under endoscopic and visualized inspection. Back and leg pain were evaluated by a numeric rating scale (NRS) and the Oswestry Disability Index. Associations of CEP avulsion with adjacent MCs, EPD, and residual back and leg pain were examined. In addition, histological features of avulsed CEP were determined using gross staining and immunohistochemical methods. RESULTS: A total of 386 patients were included. CEP avulsion was found in 166 (43%) patients, and adjacent MCs and EPD were observed in 117 (30.3%) and 139 (36%) patients. The presence of CEP avulsion was associated with greater age, adjacent MCs (OR = 2.60, 95%CI [1.61-4.19]) and EPD (OR = 1.63, 95%CI [1.03-2.57]). Among the 187 patients with ≥2 years follow-up, CEP avulsion was associated with residual back pain (OR = 2.49, 95%CI [1.29-4.82]) and leg pain (OR = 2.25, 95%CI [1.04-4.84]). Histologically, the avulsed CEP was characterized by multiple defects, apparent inflammation, and nucleus invasion, as well as the upregulation of IL-1ß, caspase-1, and NLRP3 inflammasome. CONCLUSION: CEP avulsion was associated with MCs, EPD, and residual back and leg pain after discectomy, which may be attributed to NLRP3 inflammasome related inflammations.

[Relationship between inflammatory indexes of amniotic fluid and pregnancy outcome of women with cervical incompetence].

Objective: To investigate the relationship between the level of amniotic fluid inflammatory factor and the pregnancy outcome in patients with cervical incompetence. Methods: A retrospective case-control study was conducted. Totally 110 cases of pregnant women were diagnosed as cervical incompetence for cervical dilation at the medical examination in Sun Yat-sen Memorial Hospital of Sun Yatsen University, from January 1st, 2015 to December 31th, 2016. A total of 32 patients (29.1%, 32/110) were performed cervical cerclage. According to their neonatal outcomes, they were divided into live infant group (23 cases, 72%) and dead infant group (9 cases, 28%) . The demographic and clinical data of two groups were analyzed and compared. Results: The mean peripheral blood leucocyte counts, the median amniotic tumor necrosis factor-α (TNF-α) and the median interleukin-8 (IL-8) level of two groups were (10.5±2.8) ×10(9)/L vs (13.6±3.1) ×10(9)/L, 23.80 ng/L (14.9-85.5 ng/L) vs 379.00 ng/L (70.2-418.5 ng/L) , and 3 354 ng/L (1 020-7 500 ng/L) vs 7 500 ng/L (4 210-7 500 ng/L) respectively. The differences were statistically significant (all P<0.05) . The amniotic fluid IL-1ß, IL-2 receptor, IL-6, IL-10, C-reactive protein and procalcitonin were not significantly different (all P>0.05) between two groups. Conclusions: The peripheral blood leucocyte counts, amniotic fluid TNF-α and IL-8 level are the factors affecting the pregnancy outcome in women with cervical incompetence before cervical cerclage. When IL-8 is higher than 3 580 ng/L and TNF-α is higher than 105 ng/L, the death of perinatal infants could be predicted.

miR-590-3p promotes colon cancer cell proliferation via Wnt/ß-catenin signaling pathway by inhibiting WIF1 and DKK1.

OBJECTIVE: Colon cancer is one of the most common and deadly types of gastrointestinal tumor. Despite progressive treatments, the patient prognosis has not been improved effectively. MATERIALS AND METHODS: Expression of miRNA and mRNA were tested by Realtime PCR. Cell cycle was detected by flow cytometry. Cell viability was evaluated by MTT assay. Cell spheroid formation was determined by colony assay. Wnt signaling pathway activity was evaluated by TOP/FOP ratio. Protein expression was tested using Western blot. ß-catenin binding ability was detected by ChIP assay. miRNA target gene was confirmed by luciferase assay. RESULTS: miR-590-3p was found to be overexpressed in both glioma tissues and cell lines. miR-590-3p is upregulated in colon cancer cells and tissues compared to non-tumorigenic colon cells and normal colon tissues. miR-590-3p positively regulated cell proliferation, spheroid formation, and cell cycle in LS174T cells. Conversely, inhibition of miR-590-3p reduced these effects. We confirmed that WIF1 and DKK1 are targets of miR-590-3p. Overexpression of miR-590-3p promoted TOP flash luciferase activity, enhanced nuclear ß-catenin levels and increased target genes expression of Wnt signaling pathway. The results indicated that miR-590-3p activates the Wnt/ß-catenin signaling pathway. CONCLUSIONS: We demonstrate that miR-590-3p regulates colon cancer progression via WIF1 and DKK1, which suggests that miR-590-3p may be a promising candidate for therapeutic applications in colon cancer treatment.

Synchrotron radiation-based multi-analytical approach for studying underglaze color: The microstructure of Chinese Qinghua blue decors (Ming dynasty).

In this paper, we develop a methodological approach combining macro-X-ray fluorescence and synchrotron radiation-based techniques (µXRF, full-field XANES and µXRD) to determine the composition and microstructure of underglaze decors of Qinghua porcelains (Ming dynasty). Various transition metal elements (Fe, Mn, Co) are present in the blue decoration of these ceramics and the approach proposed allows for establishing the feature of each. Thus it shows that Fe ions are distributed homogeneously over the whole glaze without any significant difference in blue and white parts. They do not play a significant role in the color. In contrast, Co ions exhibit a heterogeneous distribution with CoAl2O4 particles close to the body/glaze interphase. These particles play a key role in the blue color and, the hue variations seem in greater part to link to their density and repartition. Co dispersed in the glassy matrix is also bivalent and mainly in tetragonal coordination, leading also to a blue color. Mn ion distribution is similar to the one of Co but without presenting local high concentrations associated to Mn based particles. Mn affects the darkness of the color and for the sample without CoAl2O4 particle; it is the main color contribution. The presence of CoAl2O4 crystals was confirmed by µXRD, which revealed, in addition, a variation of cell parameters certainly linking to a Co partial substitution.

L-3-n-Butylphthalide protects rats' cardiomyocytes from ischaemia/reperfusion-induced apoptosis by affecting the mitochondrial apoptosis pathway.

AIMS: This study investigated the role of L-3-n-Butylphthalide (NBP) in cardiac protection. METHODS: The left anterior descending coronary arteries (LAD) of the rats were occluded for 30 min following by 2-h reperfusion to make the ischaemia/reperfusion models. Neonatal cardiomyocytes were cultured and subjected to hypoxia. L-3-n-Butylphthalide was administered intraperitoneally 2 h before the surgery and right after the reperfusion in the in vivo experiments or added to the culture medium in vitro. Haemodynamic parameters were recorded to evaluate the cardiac functions, triphenyltetrazolium chloride (TTC) and Evens blue staining were used to determine the area of risk and infarct area, apoptotic cell numbers were counted with terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining. Western blotting was used to determine the apoptotic protein levels and immune staining to determine the translocation of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein. RESULTS: Our research showed for the first time that L-3-n-Butylphthalide had great effects in improving cardiac hemodynamic function and decreasing cardiac infarct areas and apoptotic cell numbers in the peri-infarct areas. The apoptotic signals investigation showed that L-3-n-Butylphthalide affected the mitochondrial pathway including Bcl-2 protein expression, inhibition of caspase 3 activation and cytochrome C releasing. Besides, Glyceraldehyde-3-phosphate dehydrogenase protein translocation was inhibited by L-3-n-Butylphthalide treatment, and this effect was mediated by endogenous reactive oxygen species (ROS). CONCLUSION: L-3-n-Butylphthalide protects cardiomyocytes from ischaemia/reperfusion-induced apoptosis by antioxidant effect and affecting mitochondrial apoptotic pathway.

Influences of chloropazine, nimodipine and their combination on the toxic effects of cadmium in liver and kidney of mice.

The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium channel blocker nimodipine (NIMO) and their combination on cadmium (Cd) poisoning of mice were studied. A series of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca(2+)-Mg2+ ATPase activity in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination 1 h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that CPZ could protect kidney tissue against Cd-induced damage, as the urinary gamma-glutamyl-traspeptidase (gamma-GT) and N-acetyl-beta-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effect of CPZ and NIMO. Both CPZ and NIMO showed a considerable protective effect against the decrease in Ca(2+)-Mg2+ ATPase activity, and a synergistic action was observed. Cd content in blood was reduced significantly by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO considerably increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO exerted a synergistic action. The protective action of these two drugs might be relevant to the function of MT.

[Elimination effect of ethyl alcohol on the DCCD-induced inhibition of hydrolytic activity of H+-ATPase complex].

12.5% ethyl alcohol was added into the reaction system containing mitochondrial H(+)-ATPase complex of pig heart, which was preincubated with 0.5 microgram/ml DCCD dicyclohexylcarbodiimide) at 30 degrees C. Or the DCCD and ethyl alcohol were simultaneously incubated with H(+)-ATPase at 30 degrees C. In either case, the inhibition of the hydrolytic activity of H(+)-ATPase caused by DCCD could be completely eliminated in the presence of ethyl alcohol. If methyl alcohol was instead of ethyl alcohol, the DCCD inhibition could only be partly eliminated. In the replacement of ethyl alcohol by dimethyl sulfoxide, no elimination could be observed. After preincubation of 2 micrograms/ml oligomycin with H(+)-ATPase complex instead of DCCD, the same concentration of ethyl alcohol could not caused elimination effect, which indicates no un-coupling effect happened by ethyl alcohol. The kinetic experimental result showed that ethyl alcohol exhibits non-competitive inhibition to the hydrolytic activity of H(+)-ATPase complex. It was deduced that ethyl alcohol could result in conformational change of F1 of the complex, such as to affect the activity of the enzyme. The measurement of DPH (diphenylhexatriene) fluorescence polarization, the fluorescence labelled with N-(1-pyrenyl) maleimide and intrinsic fluorescence of H(+)-ATPase complex compared with control show that the three cases, i.e. only treated with DCCD, only treated with ethyl alcohol or treated with DCCD and ethyl alcohol, appear different conformations of H(+)-ATPase complex. But the conformation caused by DCCD and ethyl alcohol was more like that by ethyl alcohol. This is consistent with results obtained from activity of DCCD plus ethyl alcohol and only ethyl alcohol. These results mentioned above indicate that the mechanism of ethyl alcohol eliminating the DCCD-induced inhibition of H(+)-ATPase is a conformational interaction caused by DCCD and ethyl alcohol.

Adoptive transfer of murine autoimmune orchitis with sperm-specific T lymphoblasts.

A protocol was successfully developed for reproducibly transferring experimental autoimmune orchitis (EAO) to naive recipient mice with sperm-specific T lymphoblasts. Cell donors were Balb/c mice immunized about 12 days earlier with homologous epididymal sperm capacitated in vitro with complete Freund's adjuvant. Draining lymph node cells were collected and subjected to a second challenge with the same sperm antigen in vitro. Sperm-specific T lymphoblasts were isolated on Percoll density gradients and propagated in the presence of interleukin-2 for 3 days and then were transferred intraperitoneally to naive recipients. As few as 3 x 10(6) sperm-specific T lymphoblasts were able to transfer EAO, which began on day 7 as infiltration of lymphocytes and macrophages and on days 14 to 21 developed to degenerative changes of spermatids and exfoliation of germinal epithelium. These pathologic alterations resemble a delayed type of hypersensitivity. The results show that sensitized T lymphoblasts can mediate an antigen-specific, mononuclear cell-invasive lesion in autoimmune orchitis.

Aggravation of experimental cutaneous leishmaniasis in mice by administration of interleukin 3.

Previous studies from our laboratory have shown that some in vitro maintained Leishmania major-specific L3T4+ T cells were capable of exacerbating cutaneous leishmaniasis after adoptive transfer to normal syngeneic mice. Results presented in this report show that these cells released substantial amounts of interleukin 3 (IL 3) and granulocyte-macrophage colony-stimulating factors after specific stimulation in vitro. In order to assess the involvement of such lymphokines in the exacerbation of cutaneous leishmaniasis by these L3T4+ T cells, the effect of the administration of important doses of IL 3 on the course of infection with L. major was investigated. The treatment of genetically susceptible BALB/c mice with IL 3 resulted in an enhancement of the size of lesions and favored the multiplication of parasites at anatomical sites distant from the primary lesion. Although IL 3 did not modify the development of lesions in genetically resistant CBA mice, this lymphokine promoted the growth of Leishmania in lymph node draining the lesion. Finally, the addition of IL 3 to macrophages parasitized in vitro enhanced the survival of intracellular Leishmania major.