[Therapy of coronavirus disease 2019 induced acute respiratory distress syndrome is different from traditional acute respiratory distress syndrome].

Coronavirus disease 2019 (COVID-19) has become a global public health emergency threatening people's lives around the world. Although the acute respiratory distress syndrome (ARDS) induced by COVID-19 is similar to the ARDS caused by other diseases in terms of pathophysiological basis and clinical manifestations, they are also different in many aspects, which lead to different clinical therapies. Therefore, understanding the differences and similarities of ARDS induced by COVID-19 and other diseases currently are the basis for clinicians to make decisions for the treatment of COVID-19 induced ARDS.

Antiviral activity of shikonin ester derivative PMM-034 against enterovirus 71 in vitro.

Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 µg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1ß, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.

Selenium-enriched Saccharomyces cerevisiae improves growth, antioxidant status and selenoprotein gene expression in Arbor Acres broilers.

One hundred and fifty 7-day-old Arbor Acres broilers were randomly assigned into five groups: group 1 served as a control that was fed a basal diet without selenium (Se) supplementation; groups 2, 3 and 4 were fed the basal diet supplemented with 0.15, 0.5 and 1.5 mg Se as Se-enriched Saccharomyces cerevisiae (SSC) per kg of diet; and group 5 was fed the basal diet supplemented with 0.15 mg per kg of Se as sodium selenite (SS). Growth performance, glutathione peroxidase (GPX ) and superoxide dismutase (SOD) activities, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content in plasma and liver, and cellular glutathione peroxidase (GPX -1) and phospholipid hydroperoxide glutathione peroxidase (GPX -4) mRNA levels in liver were determined. Compared with group 1, groups 2-4 exhibited higher body weights (p < 0.05), lower feed/gain ratios, and higher GPX activities in plasma (p < 0.05) and GPX and SOD activities and GPX -1 and GPX -4 mRNA levels in liver (p < 0.05). Compared with group 5, group 2 exhibited higher GPX activity in plasma on day 21 (p < 0.05). Compared with group 2 and 5, group 3 exhibited lower MDA content in plasma on day 7 (p < 0.05), higher GPX activity in plasma, SOD activity and GPX -1 mRNA levels in liver on day 14 and 21 (p < 0.05), and higher GPX -4 mRNA levels on day 14 (p < 0.05). Compared with group 4, group 3 exhibited lower MDA contents in plasma on day 14 (p < 0.05) and in liver on day 21 (p < 0.05), higher T-AOC in plasma and higher GPX -1 mRNA levels on day 14 and 21 (p < 0.05), and higher SOD activity in plasma and higher SOD and GPX activities in liver on day 21 (p < 0.05). Thus, SSC improves growth and antioxidant status of broilers; the short-term bioavailability of SS was faster than that of SSC, but the long-term bioavailability of SSC was greater than SS.

Antiviral activity of shikonin ester derivative PMM-034 against enterovirus 71 in vitro

Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 μg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1β, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.

[Aluminuminduced impairment in primary cultured rat choroid plexus epithelial cells].

OBJECTIVE: To investigate the impairment in primary cultured rat choroid plexus epithelial cells (CPECs)induced by aluminum. METHODS: The choroid plexus isolated from Sprague-Dawley rats 14 days old was cut into pieces and digested by trypsin in the sterile area. The obtained single cells were cultured in DMEM with 1% epidermal growth factor and 20% fetal calf serum. Five days later, immunohistochemistry with anti-transthyretin antibody was used to identify the purity of cultured cells. The well-grown cells were treated with aluminum lactate at different concentrations (0, 100, 400, and 1 600 µmol/L for control, lowdose, mediumdose, and highdose groups). Fortyeight hours later, the cell viability, apoptotic rate, level of reactive oxygen species (ROS), and activity of superoxide dismutase (SOD)were measured in each group to evaluate the impairment in primary cultured rat CPECs by aluminum. RESULTS: More than 95% of the cultured cells were identified as CPECs. The medium-and high-dose groups had significantly lower cell viability than the control group(86.74%±4.03% vs 100%, P<0.01; 81.90%±9.17% vs 100%, P<0.01). The high-dose group had significantly lower cell viability than the lowdose group (81.90%±9.17% vs 92.92%±8.81%, P<0.01). The medium-and high-dose groups had significantly higher apoptotic rates than the control group (7.26%±0.99% vs 1.29%±0.03%, P<0.01; 22.25%±1.55% vs 1.29%±0.03%, P<0.01)and the low-dose group (7.26%±0.99% vs 1.68%±0.27%, P<0.01; 22.25%±1.55% vs 1.68%±0.27%, P<0.01). The high-dose group had a significantly higher apoptotic rate than the medium-dose group (22.25%±1.55% vs 7.26%±0.99%, P<0.01). The mediumand high-dose groups had significantly higher fluorescence intensity of ROS than the control group (22.23%±0.41% vs 17.24%±0.09%, P<0.05; 25.10%±1.13% vs 17.24%±0.09%, P<0.05)and the lowdose group (22.23%±0.41% vs 18.31%±0.21%, P<0.05; 25.10%±1.13% vs 18.31%±0.21%, P<0.05). The highdose group had significantly higher fluorescence intensity of ROS than the mediumdose group (25.10%±1.13% vs 22.23%±0.41%, P< 0.05). The low-, medium-and high-dose groups had significantly lower SOD activity than the control group[(28.65±0.74)U/g Hb vs (37.35±1.05)U/g Hb, P<0.05; (22.75±1.94)U/g Hb vs (37.35±1.05)U/g Hb, P<0.05; (13.29±0.64)U/g Hb vs(37.35±1.05)U/g Hb, P<0.05]. The medium-and high-dose groups had significantly lower SOD activity than the low-dose group[(22.75±1.94)U/g Hb vs(28.65±0.74)U/g Hb, P<0.05; (13.29±0.64)U/g Hb vs (28.65±0.74)U/g Hb, P<0.05], while the high-dose group had had significantly lower SOD activity than the medium-dose group[(13.29±0.64)U/g Hb vs (22.75±1.94)U/g Hb, P<0.05]. There were no significant differences in cell viability, apoptotic rate, level of ROS, or activity of SOD between any other two groups (P>0.05). CONCLUSION: Aluminum lactate may induce impairment in primary cultured rat CPECs. It reduces the cell viability, elevates the apoptotic rate, and causes oxidative stress.

[Improved clinical outcome of acute myeloid leukemia with FLT3-ITD mutation treated with sorafenib].

OBJECTIVE: To analyze the efficacy of sorafenib on the treatment of patients diagnosed as acute myeloid leukemia(AML) with FLT3-ITD mutation. METHODS: From January 2012 to February 2015, 42 cases of AML with FLT3-ITD mutation according to MICM (morphology, immunology, cytogenetics and molecular) diagnosis system in our hospital were retrospectively analyzed. Thirty-two cases were refractory to chemotherapy or relapsed, who were treated with sorafenib or combined with chemotherapy. Ten patients relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were retreated with sorafenib or combined with donor lymphocyte infusion (DLI) or chemotherapy. In the first group, 13 of 32 patients accepted allo-HSCT. RESULTS: The overall response rate of all 42 patients was 73.8%, including 4 (9.5%) complete molecular remission (CMR), 9 (21.4%) complete remission (CR), 8 (19%) complete remission with incomplete hematologic recovery (CRi), 10 (23.8%) partial remission (PR), and 11 (26.2%) none remission (NR). The response rate of sorafenib alone for 17 patients was 70.6%, and that of sorafenib plus chemotherapy was 66.7% (P=0.555). Thirteen patients who received allo-HSCT included 6 CMR/CR/CRi, 4 PR, and 3 NR before transplant. The 2-year overall survival (OS) rate and progress free survival (PFS) rate in all patients were 36.9% and 28.7%, and the corresponding median time were 18 months and 9 months respectively. The 2-year OS rate in 23 patients who received sorafenib combined with allo-HSCT was superior to that in 19 patients not receiving allo-HSCT (45.5% vs 23.9%, P=0.041), so was PFS rate (44.0% vs 9.7%, P=0.014). Twelve cases died of disease progression, four of infection, and one of chronic graft versus host disease after transplant. CONCLUSIONS: Sorafenib combined with chemotherapy improves response rate of AML patients with FLT3-ITD mutation. Those who are treated with sorafenib plus allo-HSCT obtain better long-term survival.

Preventive effect of electrical acupoint stimulation on lower-limb thrombosis: a prospective study of elderly patients after malignant gastrointestinal tumor surgery.

BACKGROUND: Lower deep venous thrombosis (DVT) is one of the major complications of patients with tumors or patients undergoing major surgery. Electrical acupoint stimulation, an established technique of traditional Chinese medicine (TCM), can be well combined with Western medicine to reduce the incidence of postoperative DVT, especially in elderly patients. OBJECTIVE: The objectives of this study were to assess the efficiency of electrical acupoint stimulation in the prevention of postsurgery DVT in elderly patients with gastrointestinal malignant tumors and to validate an effective and safe nursing approach that integrates TCM and Western medicine. METHODS: A total of 120 patients (none aged <60 years) who underwent malignant gastrointestinal tumor surgery between July 2005 and May 2007 were randomly divided into 3 groups: routine nursing group (group C1), graduated compression stockings group (group C2), and electrical acupoint stimulation group (group T). Hemorheological parameters (blood viscosity, etc) were measured and compared before and after surgery. RESULTS: Compared with groups C1 and C2, group T showed a significant difference in blood viscosity and blood flow velocity (P < .05). However, there were no statistical differences among groups C1, C2, and T in other hemorheological parameters. CONCLUSIONS: By speeding up the blood flow in patients' lower limbs, electrical acupoint stimulation showed a great potential to prevent symptomless DVT in elderly patients after malignant gastrointestinal tumor surgery. IMPLICATIONS FOR PRACTICE: Western medical care combined with TCM can reduce the occurrence of lower DVT in elderly patients suffering from gastrointestinal cancer. This approach may help nurses to plan effective care for elderly patients.

Combination of differentiation and T stage can predict unresponsiveness to neoadjuvant therapy for rectal cancer.

AIM: The study aimed to identify the factors predictive for extreme unresponsiveness to neoadjuvant therapy for rectal cancer. METHOD: Ninety-six patients with rectal cancer received neoadjuvant therapy (41 were treated with radiotherapy and 55 with chemoradiotherapy) before surgery. Tumour response, downstaging, pathological complete response (pCR) and disease-free survival were evaluated. RESULTS: Tumour response, downstaging and pCR occurred in 70 (72.9%), 47 (49.0%) and 14 (14.6%) patients, respectively. Univariate analyses showed that a large tumour size, T4 stage, elevated serum tumour markers, poor differentiation, radiotherapy alone and mucinous tumour were indicators of poor tumour response and/or downstaging. On multivariate analysis, chemoradiotherapy was found to be predictive for tumour response and downstaging, whereas mucinous type and T4 stage negatively affected tumour response. No variable was found to be associated with pCR, but poor differentiation and T4 stage together predicted extreme unresponsiveness with a high specificity and a high positive predictive value. Very poor disease-free survival was also observed in patients simultaneously carrying these phenotypes. CONCLUSION: Neoadjuvant chemoradiotherapy is superior to radiotherapy alone in producing a response of rectal cancer. Unresponsiveness was most likely to occur in patients with poor differentiation and T4 disease.

Biochemical and pharmacological characterization of different recombinant acid alpha-glucosidase preparations evaluated for the treatment of Pompe disease.

Pompe disease results in the accumulation of lysosomal glycogen in multiple tissues due to a deficiency of acid alpha-glucosidase (GAA). Enzyme replacement therapy for Pompe disease was recently approved in Europe, the U.S., Canada, and Japan using a recombinant human GAA (Myozyme, alglucosidase alfa) produced in CHO cells (CHO-GAA). During the development of alglucosidase alfa, we examined the in vitro and in vivo properties of CHO cell-derived rhGAA, an rhGAA purified from the milk of transgenic rabbits, as well as an experimental version of rhGAA containing additional mannose-6-phosphate intended to facilitate muscle targeting. Biochemical analyses identified differences in rhGAA N-termini, glycosylation types and binding properties to several carbohydrate receptors. In a mouse model of Pompe disease, glycogen was more efficiently removed from the heart than from skeletal muscle for all enzymes, and overall, the CHO cell-derived rhGAA reduced glycogen to a greater extent than that observed with the other enzymes. The results of these preclinical studies, combined with biochemical characterization data for the three molecules described within, led to the selection of the CHO-GAA for clinical development and registration as the first approved therapy for Pompe disease.

[Transurethral resection of bladder tumours in sodium chloride solution]. / Transurethrale Resektion von Blasentumoren in Kochsalzlösung.

BACKGROUND: Electrical transurethral resection is a well established and developed procedure. It is performed using high frequency current in a nonconductive irrigation medium. Due to these features this procedure is compromised by two possible complications: (1) spontaneous contractions of adductors caused by electrical stimulation of the obturator nerve may lead to bladder perforation, and (2) excessive flushing of the irrigation medium into the circulation can cause TUR syndrome. We present our initial experiences with a new system for transurethral resection which has overcome these potential sources of complications. The system, developed by Olympus, works with a modified guided high frequency current in 0.9% saline as irrigant. It is called TURIS (transurethral resection in saline). METHODS: A total of 35 resections of bladder tumors were performed using the TURIS technique. The operations were carried out under intravenous anaesthesia without relaxation or nerve block. During resection high frequency current passes through and active electrode (resection loop) to the sheath electrode. About 90% of the current flows through the saline to the sheath of the resectoscope, only a small amount circulates through the body of the patient. The experiences of the surgeons were documented. The resected specimens were histologically examined for artificial thermal changes and compared with a control group of conventionally resected patients. RESULTS: The handling of the TURIS resectoscope is very similar to that of well known instruments. Therefore, no special training was required for the surgeon or the theatre nurse. The control of the cutting was very efficient. Coagulation of bleeding was very good. The lack of carbonisation at the resection ground led to an excellent assessment of the resected areas. The resected tissue did not stick to the resection loop. Contraction due to nerve stimulation was not observed. No complications occurred. Histology showed no significant differences in the quantity or quality of thermal artifacts due to current. CONCLUSIONS: TURIS can be performed safety without a learning curve. Especially in TUR-B, it seems to be advantageous due to the excellent control of the extent of cutting and the lack of nerve stimulation. Quantity and quality of thermal changes in histology are not different from a conventionally resected control group.

Effects of tripcholorolide on inflammatory reaction of mouse alveolar macrophages in vitro.

AIM: To observe the effects of tripcholorolide (T4) on inflammatory reaction of mouse alveolar macrophages. METHODS: RT-PCR was used to investigate tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), IL-6, IL-10, and inducible nitric-oxide synthase (iNOS) mRNA expression in alveolar macrophages after LPS 10 mg/L and T4 500 micrograms/L treatment. ELISA was used to detect TNF alpha, IL-1 beta, IL-6, and IL-10 protein expression. Nitrite was measured by Griess reaction. RESULTS: TNF alpha, IL-1 beta, IL-6, IL-10, and nitrite increased in supernatants, when alveolar macrophages were stimulated by LPS 10 mg/L at 24 h. Both T4 500 micrograms/L and dexamethasone 100 mumol/L had inhibitory effects on the production of TNF alpha, IL-1 beta, IL-6, IL-10, and nitric oxide. The mRNA expression of TNF alpha, IL-6, IL-10, and iNOS increased at 5 h after LPS stimulation which was decreased on addition of T4 500 micrograms/L or dexamethasone 100 mumol/L. T4 had no effect on stability of LPS-induced mRNA expression in TNF alpha, IL-6, and IL-10. CONCLUSION: T4 had inhibitory effects on the expression of proinflammatory and antiinflammatory mediators.

Clinical effects and mechanism of chanlibao in accelerating second stage of labor.

To observe the clinical effects and the mechanism of Chanlibao (CLB, a preparation of Chinese herbal medicine) in accelerating second stage of labor, primiparae were divided into 3 groups at random. CLB or oxytocin (OTC) was given to the CLB group (n = 80) and the OTC group (n = 52) respectively. The third group served as controls (n = 29). The control group consisted of women experiencing natural labor and to whom no drug was given. The time of second stage of labor and prognosis of mother and newborn of different groups were observed and compared. And intrauterine pressure and fetal heart rate were monitored by means of electronic monitoring. Isolated uterine muscular tissue was used to observe the reactivity to CLB. The results showed that the time of second stage of labor and postpartum hemorrhage in the CLB group were less than those in the control group and the average intrauterine pressure in the former was higher than that in latter, so was the contraction strength of isolated uterine muscle, but with no difference as compared with the OTC group. No side effect of CLB was found. It is concluded that CLB could obviously strengthen uterine contraction and accelerate second stage of labor. Moreover, it is inexpensive, convenient and free of side effect. It can be used as a new, safe and effective alternative for improving prognosis of mother and newborn, especially those not indicated for oxytocin or profuse infusion.

[Clinical study on chanlibao in accelerating second stage of labor].

OBJECTIVE: To find out a new way to strengthen the uterine contraction and shorten the second stage of labor, for improving the prognosis of mother and newborn. METHODS: Primiparae observed were divided into three groups randomly and Chanlibao (CLB, a preparation of Chinese herbal medicine) or oxytocin (OTC) was given to the CLB group (80 cases) and the OTC group (52 cases) respectively, to the third group, as a control group (29 cases) of natural labor, without any drug was given. Time of second stage of labor (TSL) and prognosis of mother and newborn of different groups were observed and compared. And intrauterine pressure (IP) and fetal heart rate were monitored by means of electronic-monitor. RESULTS: TSL and postpartum hemorrhage in the CLB group were less than those in the control group. The average IP in former was higher than that in latter, but with no difference as compared with the OTC group. No side effect of CLB was found. CONCLUSION: CLB could obviously strengthen uterine contraction and shorten the TSL, it is cheap, convenient and with no side-effect, so it is a new safe, effective method for improving prognosis of primiparae and newborn, especially for those nonindicated in using oxytocine or infusion of fluid profusely.

[Effect of propranolol on circadian rhythm of Goldblatt hypertension in goat].

With the Goldblatt two-kidney two-clip method, persistent hypertension was reproduced in 7 goats. After hypertension was established and stabilized, a beta-receptor inhibitor Propranolol was given to the goats in the usual form of drug administration (20 mg, q 8 h) or in the form of chronotherapy (30 mg, QN). The mean value of BP was computed. The result suggested that, compared with the usual form of therapy, chronotherapy could reduce the hypertension to the same degree, but with less time and less amount of drug.

[Circadian rhythm of blood pressure in renovascular hypertensive goats treated with captopril].

Blood pressure (BP) was recorded directly and automatically by a microcomputer aid system for 48 h in normotensive and Goldblatt hypertensive goats. By population-mean cosinor fitting, significant circadian rhythms were found for SBP and DBP in both groups of goats. The BP during nighttime was higher than that during daytime in our goats. An angiotensin converting enzyme inhibitor, captopril, was given to hypertensive goats with usual schedule of drug administration (25mg, t.i.d) or form of chronotherapy (62.5 mg, given before the acrophase of BP, q.n). BP significantly decreased throughout the whole day in both treated groups. But there was no statistical difference of cosinor parameters between the effects of BP in these two groups. BP could be decreased by the method of chronotherapy with less amount of drug and less frequency of drug administration.

Two precursors of melanin-concentrating hormone: DNA sequence analysis and in situ immunochemical localization.

Two precursors to Chinook salmon (Oncorhynchus tshawytscha) melanin-concentrating hormone, an important factor in teleosts involved in the control of skin pigmentation and stress responsiveness, have been identified from DNA sequence analysis. Both precursors encode proteins of 132 amino acids and they share 107/132 amino acid identities. The biologically active 17-residue peptide is located at the C terminus of both precursors and can be liberated by proteolytic cleavage following two adjacent arginine residues. Additional putative proteolytic processing sites are located within the two precursors. Northern analysis demonstrated an intense hybridization signal of 750 nucleotides in the hypothalamus. Immunocytochemical studies as well as in situ hybridization analyses identify intensely staining cell bodies in the hypothalamus in the area of the lateral tuberal nucleus.