[A case of severe acute respiratory distress syndrome caused by inhalation injury].

A 54-year-old male patient with severe acute respiratory distress syndrome caused by inhalation injury was admitted to the First People's Hospital of Lianyungang City on June 26th, 2022. After admission, the patient received invasive mechanical ventilation (driving pressure-guided ventilator parameter setting) combined with prone position treatment immediately, but his condition continued to deteriorate. Five hours after admission, the patient received veno-venous extracorporeal membrane oxygenation (VV-ECMO) supporting treatment, treatment based on ultra-protective lung ventilation strategy combined with prone position ventilation for more than 12 hours per day. At the same time, pulse contour cardiac output monitoring technology was used to monitor cardiac index and extravascular lung water index to guide volume management, and fiberoptic bronchoalveolar lavage was performed for several times. After that, the patient was successfully weaned from VV-ECMO and ventilator, and then discharged from hospital successfully. During follow-up of one year after the injury, the patient showed no obvious respiratory symptoms, and his lung function was basically normal.

[Transcription factor EB related autophagy in the treatment of multiple myeloma and its mechanism].

Objective: To clarify the effects of bortezomib combined with or without siramesine on the proliferation of multiple myeloma cell lines, the expression changes of transcription factor EBC (TFEB) nuclear translocation and the level of autophagy, and to provide basis for further exploring the regulation mechanism of transcription factor TFEB on autophagy. Methods: The multiple myeloma cell lines RPMI8226 and U266 were cultured in vitro, and the multiple myeloma cells were treated with a certain concentration of bortezomib and siramesine. The changes of cell proliferation inhibition were detected by CCK-8 method. Real time PCR and Western blot were used to detect the relative expression of TFEB, autophagy-related factor LC3B, Beclin1, p62, LAMP1 mRNA and protein. Results: As the concentration of bortezomib increased and the duration of action increased, the proliferation inhibition rates of the two cell lines gradually increased (P<0.05) . The combination of the two drugs has a synergistic inhibitory effect on the proliferation of the above-mentioned multiple myeloma cell lines (P<0.05) . In the blank control group, single drug group, and combination drug group, the relative expression of TFEB mRNA and protein in the cytoplasm decreased sequentially (P<0.05) , and the relative expression of TFEB mRNA and protein in the nucleus increased sequentially (P<0.05) . The relative expression of autophagy-related factors LC3B, Beclin1, LAMP1 mRNA and protein increased sequentially, and the relative expression of p62 mRNA and protein decreased sequentially (P<0.05) . Conclusion: Bortezomib and siramesine can synergistically inhibit the growth of multiple myeloma cells, which is related to the increased autophagy expression in multiple myeloma cell lines and the expression of TFEB with nuclear translocation is also enhanced.

[Impact of femoral or radial approach on acute renal injury induced by repeated contrast medium in patients with coronary heart disease].

Objective: To investigate the effects of femoral approach versus radial approach on the incidence of contrast-induced acute kidney injury (CI-AKI) in patients with coronary heart disease, who received twice contrast agents within a short interval. Methods: A total of 322 patients with coronary heart disease, who admitted to the General Hospital of Northern Theater Command from January 2010 to January 2015, were included in this retrospective analysis. All patients exposed to contrast agents twice within 30 days. The patients were divided into two groups according to the approach of interventional operation: radial artery group (n=235) and femoral artery group (n=87). Serum creatinine (SCr) values were detected at 48 and 72 hours post procedure. Endpoint events were CI-AKI, which was defined as SCr increased>0.5 mg/dl (44.2 µmol/L) or relative ratio ((postoperative SCr-preoperative SCr)/preoperative SCr×100%>25%) within 72 hours after contrast agent use after excluding other causes. Clinical characteristics and the incidence of CI-AKI were compared between the two groups, multivariate logistic regression analysis was used to detect the risk factors of postoperative CI-AKI in these patients. Results: The proportion of smoking, PCI history, STEMI patients and levels of fibrinogen, fasting blood glucose, troponin T was significantly higher in femoral artery group than in radial artery group (all P<0.05). The interval between two procedure sessions was significantly longer in the femoral artery group than in the radial artery group (P=0.001). The incidence of CI-AKI tended to be higher in femoral artery group than in radial artery group after the first operation (18.6% (16/87) vs. 11.9% (28/235), P=0.133). CI-AKI incidence after the second operation was similar between the two groups (P>0.05). Multivariate logistic regression analysis showed that interventional approach was not an independent risk factor for postoperative CI-AKI in patients with coronary heart disease undergoing interventional procedures twice within 30 days (P>0.05);STEMI (OR=2.854, 95%CI 1.100-7.404, P=0.031) and diuretics use (OR=4.002, 95%CI 1.470-10.893, P=0.007) were independent risk factors for CI-AKI after the first operation. Conclusion: There is no correlation between the risk of CI-AKI and interventional approaches in patients with coronary heart disease who undergo interventional surgery twice within 30 days.

[Gene identification in a family of hereditary hemorrhagic telangiectasia].

Objective: To study the mutation of ENG, ACVRL1, and SMAD4 genes in one of a family of hereditary hemorrhagic telangiectasia (HHT) and explore its molecular pathogenesis. Methods: A family spectrum of a patient with a clinical diagnosis of HHT was surveyed. Peripheral blood samples from proband and their eldest were collected, and ENG, ACVRL1 and SMAD4 gene analysis was performed by chip capture high-throughput sequencing. The mutation detected was verified by Sanger. Results: 9 of the 71 family members were diagnosed with HHT with the main manifestation of recurrent nasal bleeding. Genetic analysis showed that the proband and the eldest son of ENG gene exon 9 frameshift mutation: c.1502-1503insGG (p.Gly501GlyfsX18) , and mutations in ACVRL1 and SMAD4 genes were not detected. Conclusion: The frameshift mutation c.1502-1503insGG (p.Gly501GlyfsX18) of the ENG gene is the genetic basis for the pathogenesis of this HHT family.

[Spatial distribution of occupational disease prevalence in Guangzhou and Foshan city by geographic information system].

Objective: To explore the occupational disease spatial distribution characteristics in Guangzhou and Foshan city in 2006-2013 with Geographic Information System and to provide evidence for making control strategy. Methods: The data on occupational disease diagnosis in Guangzhou and Foshan city from 2006 through 2013 were collected and linked to the digital map at administrative county level with Arc GIS12.0 software for spatial analysis. Results: The maps of occupational disease and Moran's spatial autocor-relation analysis showed that the spatial aggregation existed in Shunde and Nanhai region with Moran's index 1.727, -0.003. Local Moran's I spatial autocorrelation analysis pointed out the "positive high incidence re-gion" and the "negative high incidence region" during 2006~2013. Trend analysis showed that the diagnosis case increased slightly then declined from west to east, increase obviously from north to south, declined from? southwest to northeast, high in the middle and low on both sides in northwest-southeast direction. Conclusions: The occupational disease is obviously geographical distribution in Guangzhou and Foshan city. The corresponding prevention measures should be made according to the geographical distribution.

[Valproic acid activates autophagy in multiple myeloma cell lines RPMI8226 and U266].

OBJECTIVE: To investigate the effects of valproic acid (VPA) on autophagy in multiple myeloma (MM) cell lines RPMI8226 and U266. METHODS: The method of dye acridine orange (AO) was used for observing morphological changes of autophagy under fluorescence microscope; The cell proliferation inhibition was measured by MTT assay; Cells apoptosis was evaluated by flow cytometry; Autophagy-related factors LC3, Beclin1 expressions changes were detected by real-time quantitative PCR (Real-time PCR) and western blot assay. RESULTS: AO stainings as dispersively brownish red vesicles were observed both in the control and chloroquine groups, while a lot of brownish red acidic vesicles in clusters were seen in rapamycin and VPA groups. The growths of RPMI8226 and U266 cells were suppressed by VPA treatment in a dose-and time-dependent manner, after treatment with VPA for 24 h, the IC50 were (12.03 ± 0.23) mmol/L for RPMI8226 cells and (10.16 ± 0.37) mmol/L for U266 cells respectively; Poptotie cells of RPMI8226 and U266 increased in a time-dependent manner after exposure to VPA. Real-time PCR and Western blot results of RPMI8226 and U266 cells showed that gradually increased LC3, Beclin1 mRNA and protein expressions with LC3 Ⅰ to LC3 Ⅱ conversion rate after increasing the concentration of VPA and prolonging duration of action of VPA. CONCLUSIONS: The results reveal disclosed the basal level of autophagy in MM cells, VPA as a autophagy activator may be one of its actions on the treatment of MM.

[Effects of iron chelation therapy on allogeneic hematopoietic stem cell transplantation in myelodysplastic syndrome patients with iron overload].

OBJECTIVE: To investigate the effects of iron chelation therapy on hematopoietic reconstitution and related complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome (MDS). METHODS: Various clinical parameters were analyzed retrospectively in 57 MDS patients with iron overload who received allo-HSCT. According to the level of serum ferritin (SF) before transplantation divided patients into two groups: the effective treatment group (SF<1 000 µg/L) and iron overload group (SF≥1 000 µg/L). RESULTS: ①30/57 cases were received iron chelation treatment, 27/57 patients didn' t received iron chelating therapy before transplantation. 19/30 cases were in the effective treatment group, and the median SF level before transplantation was 561 (223-846) µg/L. 11/30 cases were in the iron overload group, and the median SF level before transplantation was 1 262 (1 100-2 352) µg/L. The median SF level was 1 540 (1 320-3 112) µg/L of 27 patients didn't received iron chelating therapy before transplantation. ② The rate of fully-engraftment in the effective treatment group and iron overload group was 19 cases (100.0% ) and 34 cases (89.5% ), myeloid reconstitution of 12(10-18) and 12(11-30) days respectively (P=0.441), and platelet reconstitution of 13(12-30) and 15 (10-32) days respectively (P=0.579). ③The infection risk rate of the effective treatment group was less than iron overload group [36.8% (7/19) vs 82.4% (28/34), P=0.002]. ④The incidence of aGVHD in effective treatment group was less than iron overload group [26.3%(5/19) vs 64.7%(22/34), P= 0.010]. All patients of the effective treatment group were Ⅰ/Ⅱ degree. 16 cases were Ⅰ/Ⅱ degree and 6 cases were Ⅲ/Ⅳ degree in the iron overload group. ⑤ 6 cases of iron overload group accepted iron chelation treatment early post-transplantation, and SF level decreased from 2 870 (2 205-3 580) µg/L to 1 270 (1 020-1 650) µg/L. ⑥The difference of median disease-free survival time between the effective treatment group and iron overload group was not statistically significant [28.9 (0.3-89.5) months vs 21.2(0.1-81.0) months, χ(2)=3.751, P=0.053]. CONCLUSIONS: Iron overload obviously increased transplant-related complications, and effective iron chelation therapy before transplantation significantly decreased the incidence of infection and degree of aGVHD, thereby reduced the non-relapse mortality in patients with MDS.

Oct4 and Sox2 overexpression improves the proliferation and differentiation of bone mesenchymal stem cells in Xiaomeishan porcine.

Mesenchymal stem cells derived from bone marrow (BMSCs) are a population of self-renewing multipotent cells that are capable of differentiating into various cellular lineages, and are widely employed in tissue engineering and cell therapy. Recently, clinical research involving BMSCs has become increasingly popular. In order to conduct appropriate research, it is first necessary to amplify large amounts of functional BMSCs in vitro. However, after several passages of expanding in vitro, the proliferation and differentiation potential of BMSCs gradually decline. To determine whether overexpression of Oct4 or Sox2 might prevent this decline, we transfected Oct4 or Sox2, which are essential for the pluripotency and self-renewal of embryonic stem cells, into BMSCs of Xiaomeishan porcine by a lentivirus. The results showed that overexpression of Sox2 or Oct4 BMSCs in culture media containing a basic fibroblast growth factor resulted in higher proliferation and differentiation compared to controls, suggesting that genetic modification of stemness-related genes is an efficient way to maintain the proliferation and differentiation potential of BMSCs.

Newly diagnosed acute lymphoblastic leukemia in China (I): abnormal genetic patterns in 1346 childhood and adult cases and their comparison with the reports from Western countries.

It has been generally acknowledged that the diagnosis, treatment and prognosis evaluation of leukemia largely rely on an adequate identification of genetic abnormalities. A systemic analysis of genetic aberrations was performed in a cohort of 1346 patients with newly diagnosed acute lymphoblastic leukemia (ALL) in China. The pediatric patients had higher incidence of hyperdiploidy and t(12;21) (p13;q22)/ETV6-RUNX1 than adults (P<0.0001); in contrast, the occurrence of Ph and Ik6 variant of IKZF1 gene was much more frequent in adult patients (all P<0.0001). In B-ALL, the existence of Ik6 and that of BCR-ABL were statistically correlated (P<0.0001). In comparison with Western cohorts, the incidence of t(9;22) (q34;q11)/BCR-ABL (14.60%) in B-ALL and HOX11 expression in T-ALL (25.24%) seemed to be much higher in our group, while the incidence of t(12;21) (p13;q22)/ETV6-RUNX1 (15.34%) seemed to be lower in Chinese pediatric patients. The occurrence of hyperdiploidy was much lower either in pediatric (10.61% vs 20-38%) or adult patients (2.36% vs 6.77-12%) in our study than in Western reports. In addition, the frequencies of HOX11L2 in adult patients were much higher in our cohort than in Western countries (20.69% vs 4-11%). In general, it seems that Chinese ALL patients bear more adverse prognostic factors than their Western counterparts do.

Polymorph screening: influence of solvents on the rate of solvent-mediated polymorphic transformation.

Solvent-mediated polymorphic transformation is an efficient technique to obtain the most stable polymorph. The rate of solvent-mediated polymorphic transformation of sulfamerazine at 24 degrees C in various solvents and solvent mixtures is controlled by the nucleation rate of the more stable Form II. The transformation rate is generally higher in the solvent giving a higher solubility and is low in the solvent giving a low solubility (8 mmol/L). In these solvents, because of a high interfacial energy, the metastable zone may be wider than the solubility difference between two polymorphs, such that the critical free energy barrier for nucleation cannot be overcome. In addition to the solubility, the strength of the solvent-solute interactions is also important in determining the transformation rate. For sulfamerazine, the transformation rate is lower in the solvent with a stronger hydrogen bond acceptor propensity. Because solubility is higher in the solvent with stronger hydrogen bond acceptor propensity, the balance of solubility and strength of hydrogen bonding interactions between the solute and solvent molecules determines the polymorphic transformation rate. Degree of agitation and temperature also change the polymorphic transformation rate by influencing the crystallization kinetics of the more stable polymorph.

Estimating the relative stability of polymorphs and hydrates from heats of solution and solubility data.

The transition temperature, T(t), of polymorphs is estimated from both their heats of solution and solubilities (or intrinsic dissolution rates) determined at any one temperature (e.g., ambient). At a given temperature, T, the enthalpy difference, DeltaH, between polymorphs, I and II, is equal to the difference between their heats of solution, whereas the free energy difference, DeltaG, can be estimated by the equation, DeltaG = -RTln (c(I)/c(II)) or DeltaG = -RTln (J(I)/J(II)), where c is the solubility and J is the intrinsic dissolution rate. The entropy difference, DeltaS, is evaluated as (DeltaH - DeltaG)/T. Because the heat capacity difference,DeltaC(p) between polymorphs is small enough to be neglected, the transition temperature may be estimated by the equation, T(t) = DeltaH/DeltaS. The thermodynamic stability relationships of the polymorphs (i.e., whether they are enantiotropes or monotropes) are predicted from the value of T(t) and the melting temperature. The T(t) values for auranofin, carbamazepine, chloramphenicol palmitate, cyclopenthiazide, gepirone hydrochloride, lamivudine, MK571, premafloxacin, sulfamerazine, sulfamethoxazole, sulfathiazole, and urapidil, were calculated from reported values of the heats of solution and solubilities (or dissolution rates). The stability relationships deduced from the calculated values of T(t) are in good agreement with those reported using other methods, such as differential scanning calorimetry and interpretation of melting data.

Effects of crystallization in the presence of the diastereomer on the crystal properties of (SS)-(+)-pseudoephedrine hydrochloride.

The formation and separation of diastereomers is widely used to resolve enantiomers. However, during crystallization of a chiral compound from a solution containing its diastereomer, the diastereomer may be incorporated as an impurity into the host crystal lattice, leading to changes in the thermodynamic properties and intrinsic dissolution rate of the host crystals. This hypothesis was tested by growing crystals of (SS)-(+)-pseudoephedrine hydrochloride (+PC) from aqueous solution containing various amounts of (RS)-(-)-ephedrine hydrochloride (-EC). Although the melting phase diagram of these two solid compounds, determined by differential scanning calorimetry (DSC), shows eutectic behavior, 0.034-2.4 mol% of -EC was incorporated into the crystal lattice of +PC during crystallization to form terminal solid solutions with a segregation coefficient of 0.31. In a single batch, the larger crystals contain more incorporated impurities than smaller crystals. The enthalpy and entropy of fusion measured by DSC decrease with increasing incorporation of the guest molecules into the host, indicating increases in the enthalpy and entropy of the solid. The disruption index, which indicates the disruptive effect of guest molecules in the host crystal lattice, is 60 at < or = 0.084 mol% of -EC in +PC crystals, but is only 5 at higher levels of -EC. The greater disruptive effect at lower levels of impurity incorporation may be explained by the formation of substitutional solid solutions in which the impurity molecules disrupt the hydrogen bonding network in the host crystals, whereas additional incorporated impurity may be adsorbed onto the surfaces of the mosaic blocks with reduced effect on the crystal lattice. The average intrinsic dissolution rate of impure crystals in 2-propanol is 15.8% lower than that of pure host crystals, suggesting the formation of stable solid solutions.

Long-term toxicity of modified recombinant human tumor necrosis factor in Macaca mulatta.

AIM: To study the long-term toxicity of modified recombinant human tumor necrosis factor (rhTNF-NC) in Macaca mulatta compared with recombinant human tumor necrosis factor (rhTNF). METHODS: rhTNF-NC 93, 9.3 GU/m2, and rhTNF 62 GU/m2 were injected i.v. daily to 16 Macaca mulatta for 1 month and 10 d, respectively. Hematologic, chemical, urinalysis values, ECG, specific antibody, bone marrow, and pathologic profile of organs were measured. RESULTS: No more adverse effects of rhTNF-NC were found in spite of anorexia in 4 monkeys and palpebral edema in 2 monkeys of 93 GU/m2 group. Besides, in rhTNF group, the injury of liver and kidneys, the decrease of erythron, the phlebitis, and thrombosis at injection site occurred. Both drugs caused the production of specific antibody. CONCLUSION: No serious adverse effects of rhTNF-NC were found in Macaca mulatta. The toxicity of rhTNF-NC was much lower than that of rhTNF.

[Relation of plasma soluble tumor necrosis factor receptor to tumor necrosis factor and clinical features of hepatitis B].

Plasma soluble tumor necrosis factor receptor (sTNFR) was detected by radioimmunoprecipitation-polyethylene glycol assay in 64 patients with viral hepatitis B. The levels of two distinct receptors (sTN-FR1 and sTNFR2) were significantly higher in chronic severe hepatitis (CSH) followed by chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and acute hepatitis (AH) or controls (P < 0.01). A more markedly increased sTNFR was observed in patients with high SB (> 342 mumol/L), low Pa (< 20%), and secondary infection or fatal outcome. For patients with 20% below of sTNFR levels, the increase of TNF was proportional to that of sTNFR. But, for patients with exceeding 20% of sTNFR, the ratio of TNF/sTNFR became higher. The ratio of TNF to sTNFR may be greatly indicative to determine the clinical severity and outcome. Administration of sTNFR could prevent the adverse pathologic sequence caused by the exaggerated TNF and open a new therapeutical field.

[Protective effect of prostaglandin E on hepatocytes and its value of early treatment of severe viral hepatitis].

An animal model of hepatocytic necrosis was established with injection of D-galactosamine into peritoneal cavity. Examination at regular intervals after injection showed that the level of increased serum TB, ALT and GST and the degree of histological changes in the liver were less marked in PGE-treated animals (n = 34) than those in PGE-untreated animals (n = 29), suggesting that PGE has definite protective effect for experimental hepatocytic necrosis. According to severity of the condition hepatic failure was divided into early stage, typical stage and late stage. A treatment group of 55 cases received PGE1 therapy and a control group basic support therapy only. The results showed that difference of the total effective rate was not significant between the two groups, but in the early stage of hepatic failure, the effective rate in the treatment group was markedly higher than that in the control group. In addition, incidence of hepato-renal syndrome was lower in the treatment group. We are of the opinion that division of severe viral hepatitis into three stages for evaluation of therapeutic effect is rational and useful and early use of PGE1 may show certain efficacy.

Electrolyte composition of rete testis fluid and cauda epididymal plasma and spermatozoa from rats following gossypol treatment.

This investigation was undertaken to study the potassium and sodium concentrations in rete testis fluid and cauda epididymal plasma and spermatozoa following gossypol treatment. Rats were treated orally with gossypol acetic acid at a dose of 15 mg/kg/day for 3 and 6 weeks respectively. There were not abnormal findings in the ionic concentrations of cauda epididymal plasma following 3 or 6-week-treatment. After 6 but not 3 weeks the spermatozoa in the cauda epididymidis were rendered almost completely immotile and malformed with a significant reduction in their potassium concentration and rise in their sodium concentration. No abnormal findings in the morphological picture of the germinal epithelium were observed under such circumstances and fluid and sperm from the rete testis were normal. Therefore, a direct action of gossypol may be exerted locally on the spermatozoa in the epididymis.