Diabetes is a common disease,the complications caused by hyperglycemia have a serious impact on the quality of life of patients.The wound healing after skin injury in diabetic patient is affected by many factors.This article reviews various factors related to angiogenesis and wound healing in diabetes,including insulin,endogenous hydrogen sulfide,hypoxia inducible factor-1α and tumor necrosis factor-α.These findings may provide a new theoretical basis for the treatment of diabetic wound healing,foot ulcer and other complications.

Objective To investigate the role and the mechanism of ppk1 gene (coding for polyphosphate kinase 1) in oxidative stress resistance in uropathogenic Escherichia coli (UPEC).MethodsMutant strains with ppk1-deletion (△pk1) and complemented strains (△pk1-C) were constructed based on the UPEC strain CFT073.A comparative analysis was conducted to analyze survival rates of CFT073, △pk1 and △pk1-C strains at different time points while they were under oxidative stress.Differences in protein expression between CFT073 and △pk1 strains were analyzed using mass spectrometric analysis.Differences between CFT073 and △pk1 strains in expression of katG and katE genes were analyzed using real-time quantitative RT-PCR.Results The survival rate of △pk1 strains was lower than that of CFT073 strains at every time point, while the survival rate of △pk1-C strains was basically the same as that of CFT073 strains.Gel image analysis and mass spectrometric analysis revealed that six proteins were down-regulated and one was up-regulated in △pk1 strains as compared with those in CFT073 strains.Expression of the catalase-coding genes katG and katE in △pk1 strains were respectively (20.5±8.2)% and (20.9±6.9)% of those in CFT073 strains (P<0.05).Conclusion The ppk1 gene plays an important role in oxidative stress resistance in UPEC by modulating the expression of catalase-coding genes katG and katE.

BACKGROUND:There are a lot of adipose-derived stem cel s in the vascular stroma. These cel s are shown to play a very important role in the fat granule transplantation.
OBJECTIVE:To explore the role of adipose-derived stem cel s in the fat granule transplantation.
METHODS:Normal adipose tissues were obtained from 10 male BALB/C mice, SPF grade. Adipose-derived stem cel s and fat granules were extracted from the abdominal fat tissues. Another 24 nude mice acted as recipients and were assigned into control, fat granule transplantation or mixed transplantation (adipose-derived stem cel s+fat granules) groups. In the latter two groups, fat granule suspension and suspension of fat granules and adipose-derived stem cel s were injected into the shoulder of rats, respectively. In the control group, the same volume of cel medium was injected. Four weeks later, separated plasma and grafts were taken out for indicator measurement.
RESULTS AND CONCLUSION:Compared with the fat granule transplantation group, the mixed transplantation could remarkably increase the weight of grafts, while reduce the absorption of grafted fat tissues (P<0.01). After transplantation, the highest level of vascular endothelial growth factor in the plasma was obtained in the mixed transplantation group fol owed by fat granule transplantation group and control group (P<0.01). Level of basic fibroblast growth factor and microvessel density were significantly higher in the mixed transplantation group than the fat granule transplantation group (P<0.01). Better cel morphology and higher number of fat droplets were found in the mixed transplantation group compared with the fat granule transplantation group. Al these results indicate that adipose-derived stem cel transplantation can remarkably promote the expression of basic fibroblast growth factor, improve graft microcirculation, and improve morphology and function of fat granules.

Aim To investigate the effect of indirubin derivative PHⅡ-7 and TRAIL on proliferation in breast cancer cell MCF-7 and its MDR counterpart MCF-7/ADR and the mechanism.Methods Growth inhibition rate was examined respectively by MTT assay under treatment with TRAIL or PHⅡ-7 or in combination. Cell apoptosis and ROS production were examined by flow cytometry.The change of TRAIL receptors(DR4/DR5 )in mRNA was analysed by realtime PCR.Re-sults IC50 of PHⅡ-7 on MCF-7 and MCF-7/ADR was (4.49 ±1.55 ),(3.44 ±0.90 )μmol · L-1 respec-tively;MDA-MB-231 was TRAIL sensitive cell line, and apparently TRAIL induced apoptosis in MDA-MB-23 1 .Low concentration of PHⅡ-7 in combination with TRAIL could augment TRAIL-induced cytotoxic effect including apoptosis while TRAIL or PHⅡ-7 treatment alone had limited cytotoxity to those cells.Besides, PHⅡ-7 at this concentration had little toxicity to hu-man peripheral blood mononuclear cells even if in com-bination with TRAIL.PHⅡ-7 generated ROS produc-tion inside MCF-7 and MCF-7/ADR cells and up-regu-lated DR4/DR5 expression concentration dependently. Once upon ROS scavenger NAC involved,the effect of TRAIL receptors up-regualtion by expression was abro-gated.Conclusions PHⅡ-7 at low concentration could improve the sensitivities of breast cancer cell MCF-7 and MCF-7/ADR to TRAIL,the mechanism of which may be the ability of ROS production by PHⅡ-7 help up-regulated TRAIL receptor DR4,DR5 .Our re-search set a solid foundation for PHⅡ-7 in combination with TRAIL in future clinical application.

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.

Three cases of swimming pool granuloma are reported.Case 1:a 40-year-old female presented with a 2-month history of nodules and plaques on the right hand and forearm.She was a tropical fish salesperson but denied trauma history.Skin examination revealed multiple irregularly sized,dark-red nodules and plaques on the joints of right fingers,wrist,and elbow,as well as multiple subcutaneous nodules simulating strings of beads on the right upper limb.Case 2:a 48-year-old female presented with a 2-month history of nodules and plaques on the left hand and forearm.There was a history of trauma due to tropical fish tank and filter cleaning.Physical examination showed multiple deep purple plaques and painless subcutaneous nodules scattered on the left hand,wrist,and upper limb.Case 3:a 39-year-old male presented with a 3-month history of nodules on the fingers of both hands.There was no history of trauma,but he was a tropical aquarist.Skin examination revealed multiple soybean-sized dark-red nodules on the extensor aspect of interphalangeal joints of both hands.Fungal examinations yielded negative results in the 3 cases,while histopathology revealed infectious granuloma with a mixed inflammatory cell infiltrate.All of the cases showed positive results in purified protein derivative (PPD)skin test.Mycobacterium marinum was isolated from the lesional tissue of Case 1 and 2,but not from Case 3.All the patients were diagnosed with swimming pool granuloma,and given anti-atypical mycobacterial therapy including oral rifampin and clarithromycin.The lesions disappeared after 1 to 3 months of treatment,with the treatment course varying from 2 to 5 months.No recurrence was observed during a 3- to 12-month follow-up.

Objective To investigate the application value of multi-slice spiral CT on the congenital malformation of coronary sinus. Methods MSCT finding of 98 patients with coronary sinus malformation confirmed by surgery were retrospectively analyzed,and the cases were divided into four categories based on the Mantini theory and comparison was made between the diagnosis from ultrasound and CT.A 2 × 2 table for Chi-square test was also used for statistics analysis.Results Among 98 patients,there were 72 patients with persistent left superior vena cava reflowed to right atria through coronary sinus,with 48 patients diagnosed by ultrasound and 72 patients by MSCT; there were 13 patients with anomalous pulmonary venous connection to coronary sinus,with 12 patients diagnosed by ultrasound and 13 patients by MSCT diagnosis; there were 10 patients with unroofed coronary sinus syndrome,with 6 patients diagnosed by ultrasound and 8 patients by MSCT,there were 2 patients with coronary sinus atresia,all diagnosed by MSCT; there were 1 patient with coronary sinus anomaly reflow to left arita.The significant difference between 2 modalities (x2 =22.7,P＜0.01) shows that CT is superior to ultrasound.Conclusion MSCT is much more better than ultrasound in the diagnosis of malformation of coronary sinus and it can provide reliable diagnosis prior to surgery or interventional therapy.

The epidemic of coronavirus disease 2019 (COVID-19) puts higher demands on critical care medicine. Lots of studies have been conducted to solve COVID-19-related problems. Therefore, we reviewed the annual progress for COVID-19-related issues including antivirals threapies, respiratory support and immunomodulatory therapies and other critical issues, including the effect of antibiotic on mitochondrial damage and its relationship with sepsis, the goal and direction of antimicrobial de-escalation, drug prophylaxis of constipation, bleeding in gastrointestinal disorders and management of critical illness in the informalization era and so on. We hope to provide reference for clinical and scientific research work of the intensivists.

OBJECTIVETo explore the clinical phenotype of a family affected with congenital dysfibrinogenemia and potential mutations underlying the disease.

METHODSCoagulation testing and hepatorenal function testing were conducted on 18 individuals from three generations. Plasma fibrinogen was extracted and analyzed with SDS-PAGE electrophoresis. All of the exons and flanking sequences of fibrinogen FGA, FGB, FGG genes were analyzed by PCR, and the products were subjected to Sanger sequencing.

RESULTSHepatorenal function, prothrombin time and activated partial thromboplastin time of the proband were all normal. However, his thrombin time was significantly prolonged. Fibrinogen activity was decreased, while the concentration of antigen was in the normal range. The results of his mother, brother, and nephew were similar. DNA sequencing has confirmed that the proband, his mother, brother, and nephew have all carried a g.5877G>A mutation in the exon 8 of the FGG gene, which resulted in replacement of arginine (Arg) by histidine (His) at position 275.

CONCLUSIONThe Arg275His mutation of the fibrinogen gamma chain probably underlies the pathogenesis of congenital dysfibrinogenemia in this family.

Adult ; Afibrinogenemia ; genetics ; metabolism ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Female ; Fibrinogen ; genetics ; metabolism ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Mutation, Missense ; Pedigree ; Point Mutation

Objective To investigate the clinical efficacy and safety of Danshu Capsule in the treatment of chronic cholecystitis and gallstones through a large-sample, multicenter, open-label real-world research. Methods A total of 9579 patients with chronic cholecystitis and/or gallstones who were treated in 329 hospitals of China from January 2017 to December 2019 were enrolled and divided into gallstones group with 1148 patients, chronic cholecystitis group with 5360 patients, and chronic cholecystitis+gallstones group with 3071 patients.All patients were treated with oral administration of Danshu Capsule at a frequency of 1-2 capsules/time, three times a day after meals, for 4 consecutive weeks.Abdominal pain, biliary dyspepsia, traditional Chinese medicine (TCM) syndromes, and imaging findings of the biliary system were recorded before and after treatment to evaluate the efficacy of medication, and adverse drug reactions were monitored to evaluate the safety of Danshu Capsule.The Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment, and the Wilcoxon rank-sum test was used for comparison between any two groups.The paired chi-square test was used for comparison of categorical data before and after treatment; the Kruskal-Wallis H method was used for comparison between multiple groups, and the Logistic regression analysis and the Nemenyi test was used for further comparison between two groups. Results After treatment with Danshu Capsule, all patients had significant reductions in the overall incidence rate of pain induced by lipid meal ( χ 2 =32.422, P < 0.001), the frequency, duration, and degree of pain ( Z =-1.985, -2.887, and-3.178, all P < 0.05), the symptom scores of abdominal distension, abdominal fullness, belching, and nausea (all P < 0.001), and the total symptom score of biliary dyspepsia ( Z =-4.128, P < 0.001);there were also significant reductions in the TCM syndrome scores of right upper quadrant pain, bitter taste, acid regurgitation, chest distress, abdominal distension, poor appetite, and heaviness of limbs (all P < 0.05) and a significant reduction in total TCM syndrome score ( Z =3.860, P < 0.001).Subgroup analysis showed that after treatment, the gallstones group, the chronic cholecystitis group, and the chronic cholecystitis+gallstones group had significant reductions in the degree, frequency, and duration of pain, the symptom score of biliary dyspepsia, and TCM syndrome score (all P < 0.05), as well as a significant reduction in the number of patients with pain induced by lipid meal ( P < 0.001).The chronic cholecystitis group had significantly greater reductions in the score of pain frequency, the score of pain duration, the score of pain degree compared with the other two groups (all P < 0.05).Ultrasound examination showed that after treatment, all patients had significant reductions in poor sound transmission of gallbladder, gallbladder wall thickness, incidence rate of gallbladder wall thickening or roughness, and the number and size of gallstones (all P < 0.05).Danshu Capsule showed an overall response rate of 74.75% in the treatment of gallbladder wall lesion and an overall response rate of 67.40% in the treatment of gallstones.A total of 84 patients reported adverse events, mainly gastrointestinal symptoms, and the overall incidence rate of adverse reactions was 0.87%. Conclusion Danshu Capsule can significantly alleviate the symptom of pain and improve the symptoms of biliary dyspepsia, TCM syndrome, and gallbladder imaging findings in patients with chronic cholecystitis and/or gallstones, with a low incidence rate of adverse reactions, and therefore, it is a safe and effective drug for the treatment of chronic cholecystitis and gallstones.