Aim To investigate the antibacterial activity and anti-resistant mutation ability of Qiguiyin decoction (a traditional Chinese herbal formula) combined with levofloxacin against pseudomonas aeruginosa byantibacterial experiment in vitro and serum pharmacology. Methods The minimal inhibitory concentrations (MICs) of levofloxacin and Qiguiyin decoction were detected respectively by the broth dilution technique.The MIC of the combination of two drugs was determined by the micro chessboard dilution method. The effects of combined drugs on enhancing the antibacterial activity of different strains were evaluated respectively by calculating the fractional inhibitory concentration index (FICI). The drug-containing serum of levofloxa-cin group, Qiguiyin decoction group, Qiguiyin decoction combined with levofloxacin group and control group was prepared. The antibacterial rate, MIC and MBC of 10% ~ 90% serum against the two strains were determined. Results Combined with Qiguiyin decoction, MIC of levofloxacin against pseudomonas aeruginosa (standard/resistant) decreased significantly, 0. 5 < FICI ^ 1. With the increase of the proportion of serum, the inhibitory rate of 10% ~ 90% drug-containing serum to pseudomonas aeruginosa (standard/resistant) increased gradually.compared with the control group, the inhibitory effect of the Qiguiyin group on bacteria was significantly enhanced. The MIC

OBJECTIVES: To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance. METHODS: A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission. RESULTS: A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05). CONCLUSIONS Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.
Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Hyperbilirubinemia, Neonatal/therapy* ; Infant, Newborn ; Obstetrics ; Patient Discharge ; Pregnancy ; Retrospective Studies

Post-transcriptional modifications of eukaryotic mRNA can regulate the genetic information of many genes, and the study of m

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

【Objective】 To explore the effect of histone H3K27me3 methyltransferase Ezh2 deficient in mesenchymal stem cells(MSC) on the differentiation of mouse skeletal muscle cells and mitochondria inside them. 【Methods】 Ezh2 conditional knockout mice(Ezh2^F/FPrx1-Cre) were constructed. In 6-week-old mice, HE staining, modified Gomori trichrome staining and NADH-TR staining were used to observe cell morphology and mitochondria. The ultrastructures of skeletal muscle cells and mitochondria were observed under electron microscope. Western blot was used to detect the protein expression of Ezh2, H3K27me3, Myogenin, Myosin, Desmin and CytC. The expression of differentiation related genes and mitochondrial related genes in skeletal muscle were detected by Realtime RT-qPCR. The expression of CytC in skeletal muscle was detected by immunohistochemistry, and ATP content in skeletal muscle was detected by ATP content assay kit. HE staining and NADH-TR staining were used to observe the skeletal muscle of 2-week-old mice. In 6-weekold mice, the content of Ezh2 protein in brown adipose tissues was detected by Western blot, and the mitochondria were observed under electron microscope. 【Results】 The content of Ezh2 and H3K27me3 protein in the skeletal muscle of the knockout group decreased significantly. In the knockout group, the muscle fibers of skeletal muscle were not uniform in thickness; some nuclei moved inward, and skeletal muscle markers Myogenin and MhcIIb mRNA expression decreased significantly(P < 0.05). Myogenin protein expression decreased, but NADH-TR and CytC immunohistochemical staining showed that mitochondria increased. Under electron microscope, the myofibrils in the knock-out group were of different thickness, and the number of mitochondria under the cell membrane and between myofibrils increased significantly, which were clumped. There was no edema in mitochondria and no obvious decrease in cristae. The expression of CytC, Tfam, Pgc1α mRNA and CytC protein increased in the knockout group(P < 0.05), but the content of ATP decreased significantly(P < 0.05). However, there was variation in muscle fiber thickness but no difference in the content of NADH of 2-week-old mice. Under electron microscope, there was no increase in the number or abnormal morphology of mitochondria in brown adipocytes of 6-week-old mice. 【Conclusions】 Ezh2 is necessary in the differentiation of mouse skeletal muscle cells in MSC stage and maintain the ATP production of mitochondria. In Ezh2 deficient mice, the ATP production of mitochondria decreased and the number of mitochondria increased compensatorily.

Objective:To observe the effect of long-term administration of emodin on the kidney toxicity of mice, explore its possible toxic mechanism, and provide some basis for clinical rational drug use and further research. Method:The 30 Kunming mice, half male and half female, were randomly divided into 3 groups:control group, emodin low dose group and emodin high dose groups (0.8, 1.6 g·kg^-1), 10 mice in each group. Continuous intragastric administration was given for 11 weeks. During administration, the general situation of the mice was observed and recorded. After treatment, the serum urea nitrogen (BUN), creatinine (SCr), malondialdehyde (MDA), superoxide dismutase (SOD) tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) were detected. Kidney index was calculated and glutathione peroxidase (GSH-Px) and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio were measured. The kidneys were taken for histopathological examination and the protein expression levels of transforming growth factor-β₁(TGF-β₁) and cysteine aspartic acid specific protease-3 (Caspase-3) were then detected by immunohistochemistry assay. Result:As compared with control group of the same sex, the weight of mice in the administration groups was decreased significantly, renal index was decreased while BUN and SCr levels were increased significantly (P<0.05,P<0.01); activity of SOD was decreased significantly (P<0.05, P<0.01); content of TNF-α was increased significantly (P<0.05, P <0.01), while the content of GSH-Px and the ratio of GSH/GSSG were decreased significantly in high emodin group(P<0.05), and the expression of Caspase-3 was increased significantly in high emodin group (P<0.05). Renal histopathology:tubule epithelial cells swelling, tubulointerstitial protein tube type, hyperemia and lymphocytic small focal hyperplasia were observed in emodin high dose group, but the performance above was not obvious in low dose group. Conclusion:The long-term administration of emodin at a large dose would show toxicity effect on mice kidney, and the toxicity was obvious at the dose of 1.6 g·kg^-1·d^-1, but there was no significant difference between the sexes. The mechanism of its potential toxicity may be related to the disorder of oxidation system, the injury of oxidative stress, the triggering of inflammatory reaction, and the apoptosis of cells.

Objective:To study nephrotoxicity induced by long-term administration of different doses of aloe-emodin in mice, and explore its mechanism. Method:A total of 30 male and female Kunming mice were randomly divided into normal control group, and low-dose aloe-emodin group,high-dose aloe-emodin group (0.8,1.6 g·kg^-1). Every dose of group was administered intragastrically for 11 weeks,twice daily. effect of serum urea nitrogen (BUN),creatinine (SCr),superoxide dismutase (SOD),malondialdehyde (MDA),Glutathione (GSH/GSSG) and Glutathione Peroxidase (GSH-Px) levels were detected by biochemical kits according to manufacturer's instruction. Enzyme-linked immune assay was used to determine serum tumor necrosis factor (TNF)-α and interleukins(IL)-6 levels. Hematoxylin eosin (HE) staining was used to detect renal pathological changes in kidney tissues, and cysteine aspartic acid specific protease(Caspase)-3 and transforming growth factor(TGF)-β₁ proteins were determined by immunohistochemistry. Result:According to results,compared with normal control group,the levels of BUN and SCr in serum with high-dose aloe-emodin were increased. The renal tubules in low-dose group were mildly injured,while renal tubules and glomeruli of high-dose group were moderately damaged. Compared with normal control group,the level of SOD was significant decreased (P<0.05), MDA was increased (P<0.05),the levels of GSH/GSSG in kidneys of high-dose groups were decreased (P<0.05). In high-dose group,the expression of Caspase-3 protein was increased in kidneys,especially in males (P<0.05). Compared with normal control group,the levels of TNF-α and IL-6 were increased,the expression of TGF-β₁ protein in kidneys was increased in low-dose and high-dose groups (P<0.05). Conclusion:results show that 1.6 g·kg^-1 aloe-emodin was administered intragastrically for 11 weeks,which had toxic effects on kidney in mice. The mechanism may be related to oxidative stress,apoptosis and TGF-β₁ protein expression.

Objective:To observe effect of long-term administration of rhein on the kidney toxicity of mice, and explore its possible toxic mechanism, in order to provide some basis for rational clinical drug use and further research. Method:The 30 Kunming mice (half male and half female) were randomly divided into 3 groups:control group, low-dose rhein group and high-dose rhein group (0.175,0.35 g·kg^-1), with 10 mice in each group. The intragastric administration lasted for 60 days. During administration, general situations of the mice were observed and recorded. Serum urea nitrogen (BUN), creatinine (SCr), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected after drug withdrawal. Kidney index was calculated, and glutathione peroxidase (GSH-Px) and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio were measured. The kidneys were collected and histopathologically examined, and the protein expressions of transforming growth factor beta (TGF-β₁) and cysteine aspartic acid specific protease-3 (Caspase-3) were detected by immunohistochemistry. Result:Compared with the control group of the same sex, BUN and SCr of the administration group increased significantly(P<0.05,P<0.01). In the high-dose group, the activity of SOD decreased significantly(P<0.05,P<0.01), while the expressions of TNF-α and Caspase-3 increased significantly(P<0.05). In the male group, the renal index was significantly decreased(P<0.05,P<0.01), the GSH-Px content in the male high-dose group was significantly decreased(P<0.05), whereas the expression of TGF-β₁ was increased(P<0.05). The histopathological changes of kidney were observed by hematoxylin-eosin (HE) staining. In the high-dose group, protein tubules were found in renal tubule lumen, glomerular and interstitial capillary congestion, tubule epithelial cell swelling and small focal proliferation of lymphocytes, and the pathological changes were more serious in male mice. The above performances in the low-dose group was less significant than those in the high-dose group. Conclusion:The toxicity of rhein in the kidney of mice was obvious at the dose of 0.35 g·kg^-1·d^-1, and the toxicity in male organism is more obvious. The mechanism of its potential toxicity may cause the imbalance of glutathione antioxidant system, induce excessive oxidation, trigger inflammatory reaction, activate the expression of Caspase-3, and then induce apoptosis.

OBJECTIVETo investigate the relationship between NK cell count/activity and acute graft-versus-host disease (aGVHD) in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSA total of 26 patients who had undergone allo-HSCT from January to July 2015 were enrolled in this study. The NK cell count/activity in the peripheral blood of recipients on day 30 after allo-HSCT were monitored by using 4-color flow cytometry. The incidence of aGVHD in patients was evaluated by clinical manifestation combinating with related pathologic indicators, and the relationship between NK cell count/activity and aGVHD were analyzed.

RESULTSIn the aGVHD group and the no-aGVHD group, the NK cell count and activity on days 30 after allo-HSCT were 655±216 cells/µl vs 1169±372 cells/µl(P=0.002) and 7.3±3.6% vs 9.0±3.6% (P=0.008). In the II-IV grade aGVHD group and the 0-I grade aGVHD group, the NK cell count/activity were 617±220 cells/µl vs 1081±399 cells/µl (P=0.001) and 4.2±1.7% vs 8.3±3.5%(P=0.001). As compared with the 0-I grade aGVHD group, patients in the II-IV grade aGVHD group had higher relapse rate (57% vs 5%)(P=0.010) , lower 1-year progression-free survival(PFS) rate (43% vs 84%)(P=0.010).

CONCLUSIONNK cell count/activity on day 30 after allo-HSCT were closely relates with aGVHD, which may be a potential marker for aGVHD and can provide a new target for aGVHD therapy.

BACKGROUND: Brain injury can promote fracture healing is becoming an issue of concern, but the underlying mechanism remains unknown.OBJECTIVE: To establish a model of cerebral injury combined with right tibial fracture, and to investigate the cerebrospinal fluid and serum levels of calcitonin gene-related peptide, nerve growth factor and insulin-like growth factor-1.METHODS: New Zealand white rabbits were randomly divided into four groups: group A: blank control group;group B: simple brain injury group; group C: simple tibial fracture group; group D: tibial fracture combined with brain injury. The cerebrospinal fluid and serum levels of calcitonin gene-related peptide, nerve growth factor and insulin-like growth factor-1 were detected at different time points. The rabbits in the groups C and D were sacrificed at 1, 4 and 8 weeks after modeling to remove the whole tibia, and scanned by X-ray. The callus volume was calculated, and the pathological changes were analyzed.RESULTS AND CONCLUSION: The fracture healing was faster in the group D than the group C. The callus volume,trabecular width, trabecular area ratio, and the number of newly born vessels in the group D were significantly higher than those in the group C at 4 weeks after modeling (P < 0.05). The cerebrospinal fluid and serum levels of calcitonin gene-related peptide, nerve growth factor and insulin-like growth factor-1 in the group D were significantly higher than those in the group C (P < 0.05), and the cerebrospinal fluid levels reached the maximum values earlier than did the serum levels. Furthermore, in the group D, the calcitonin gene-related peptide level was increased earlier than the other two factors. To conclude, calcitonin gene-related peptide, nerve growth factor and insulin-like growth factor-1 are essential factors involved in promoting fracture healing after traumatic brain injury, and moreover calcitonin gene-related peptide shows a stronger ability than the other factors.