Objective:To investigate the effects and mechanisms of zinc ion-loaded composite hydrogel (hereinafter referred to as the zinc-containing hydrogel) on infected full-thickness skin defect wounds in diabetic mice.Methods:This study was an experimental study. A poly (glycerol sebacate)-co-poly(ethylene glycol)-g-catechol prepolymer/quaternized-chitosan hydrogel (hereinafter referred to as the simple hydrogel) and a solid-state zinc-containing hydrogel with porous and good adhesion by adding zinc ions to the simple hydrogel were prepared. The release rate of zinc ions from the zinc-containing hydrogel after immersion in phosphate buffer solution (PBS) for 14 days was calculated. The concentration of methicillin-resistant Staphylococcus aureus (MRSA) cultured for 2 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was measured. The scavenging ability of the simple hydrogel, zinc-containing hydrogel, and PBS for 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2, 4, 6-trinitrophenyl) hydrazyl (DPPH) was detected using microplate reader to reflect the ability of oxygen free radical removal. The length of vessels formed by human umbilical vein endothelial cells (HUVECs) cultured for 24 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was measured. The cell viability of L929 cells cultured for 24 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was detected using the cell counting kit-8. The mouse red blood cell suspension was divided into blank control group treated with PBS, simple hydrogel group, zinc-containing hydrogel group, and Triton X-100 group treated with corresponding solution. Hemolysis was detected using microplate reader after 2 hours of treatment, and the hemolysis rate was calculated. All experiments had a sample size of 3. Twenty-one C57BL/6J mice aged 6-8 weeks were taken, and a full-thickness skin defect wound was prepared in the symmetrical position on the back spine and infected with MRSA. Mice were divided into blank control group treated with PBS, simple hydrogel group, and zinc-containing hydrogel group treated with the corresponding hydrogel. Three days after injury, bacterial concentration in the wounds were measured in all groups of mice ( n=4). On day 0 (immediately), 3, 7, and 14 after injury, the wound infection status of mice was generally observed and the wound healing rate was calculated ( n=5). Hematoxylin-eosin staining and Masson staining were used to detect new epithelium and collagen formation in the wounds of mice on day 14 after injury. Immunofluorescence staining was used to detect neovascularization and distribution of M2 macrophages in the wounds of mice. Results:After immersion for 14 days, the release rate of zinc ions of the zinc-containing hydrogel was (70.5±4.6)%. Compared with the zinc-containing hydrogel, the bacterial concentration was significantly increased after 2 hours of culture with PBS and the simple hydrogel ( P<0.05). The DPPH scavenging rate of the zinc-containing hydrogel was significantly higher than that of PBS and the simple hydrogel (with P values all <0.05). The length of vessels formed by HUVECs cultured for 24 hours with the zinc-containing hydrogel was significantly longer than that cultured with PBS ( P<0.05). Compared with PBS and the simple hydrogel, the cell viability of L929 cells cultured for 24 hours with the zinc-containing hydrogel was significantly higher ( P<0.05). After 2 hours of incubation, compared with that in Triton X-100 group, the hemolysis rate of red blood cells in blank control, simple hydrogel, and zinc-containing hydrogel groups was significantly reduced ( P<0.05); and the hemolysis rate of red blood cells in the latter three groups was similar ( P>0.05). On day 3 after injury, the bacterial concentration in the wounds of mice in zinc-containing hydrogel group was significantly lower than that in blank control and simple hydrogel groups (with P values all <0.05). From day 3 to day 14 after injury, the wounds of mice in all the three groups were gradually healing, and on day 14 after injury, the wounds of mice in the zinc-containing hydrogel group were basically healed. On day 7 after injury, the wound healing rate of mice in zinc-containing hydrogel group was (72.4±8.4)%, which was significantly higher than that of blank control and simple hydrogel groups, being (31.6±6.7)% and (44.7±5.4)%, respectively(with P values all< 0.05). On day 14 after injury, the wound healing rate of mice in zinc-containing hydrogel group was (92.7±4.3)%, which was significantly higher than (73.5±7.4)% in blank control group ( P<0.05). On day 14 after injury, compared with that in blank control and simple hydrogel groups, the newly formed epidermis in mice wound of zinc-containing hydrogel group was longer and thicker, with more collagen deposition, and a more abundant distribution of new vessels and M2 macrophages. Conclusions:The zinc-containing hydrogel exhibits good biocompatibility, oxygen free radical scavenging capacity, and antimicrobial effects both in vitro and in vivo, as well as angiogenic promotion capability. It can provide sustained release of zinc ions to promote re-epithelialization and collagen synthesis, thus enhancing the healing of infected full-thickness skin defect wounds in diabetic mice.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To explore the influence of inhalation injury on fluid resuscitation of massive burn patients during shock stage.Methods:A total of 74 massive burn patients (65 males and 9 females, aged 21 to 65 years) admitted to the Second Affiliated Hospital of Air Force Medical University ( n=57) and Yan′an University Affiliated Hospital ( n=17) from May 2009 to December 2019 were enrolled in this retrospective cohort study. Patients were divided into inhalation injury group ( n=56) and non-inhalation injury group ( n=18) based on clinical symptoms, vital signs, and results of bronchofibroscopy. Then 26 patients in inhalation injury group and 13 patients in non-inhalation injury group were 1∶2 matched by case-control matching based on the difference of total burn surface area. The total fluid replacement coefficient, crystalloid replacement coefficient, colloid replacement coefficient, glucose input volume, ratio of crystalloid to colloid, urine volume, and cumulative ratio of input to output volume during the first 24 h post injury, the second 24 h post injury, and the third 24 h post injury, heart rate, respiratory rate, mean arterial pressure (MAP), and hematocrit (HCT) at post injury hour (PIH) 24, 48, and 72 were recorded and compared between the two groups. Data were statistically analyzed with analysis of variance for repeated measurement and Bonferroni correction, t test, Fisher′s exact probability test, and Mann-Whitney U test. Results:(1) After matching, during the first to third 24 h post injury, the total fluid replacement coefficient and glucose input volume of patients in inhalation injury group were significantly higher than those in non-inhalation injury group ( F=4.202, 10.671, P<0.05 or P<0.01). During the first, second, and third 24 h post injury, the total fluid replacement coefficient, crystalloid replacement coefficient, colloid replacement coefficient, and ratio of crystalloid to colloid were similar between the patients in two groups( t=-1.336, -1.452, -1.998; -0.148, 0.141, 0.561; 0.916, -0.046, -0.509; -1.024, 0.208, 0.081, P>0.05). During the first, second, and third 24 h post injury, the glucose input volume of patients in inhalation injury group were respectively (2 996±1 176), (2 659±1 030), and (2 680±1 509) mL, which were significantly higher than (2 125±898), (1 790±828), and (1 632±932) mL in non-inhalation injury group ( t=-2.334, -2.639, -2.297, P<0.05). (2) After matching, in overall comparison between groups, during the first to third 24 h post injury, the urinary output volumes and cumulative ratios of input to output volume of patients in inhalation injury group were significantly lower or higher than those in non-inhalation injury group, respectively ( F=12.158, 9.111, P<0.01). At PIH 24, 48, and 72, heart rate of patients in inhalation injury group were significantly higher than those in non-inhalation injury group ( F=4.675, P<0.05). There were no statistically significant differences in heart rate, respiratory rate, MAP, and HCT between patients in the two groups at PIH 24 and 48 ( t=-0.039, -1.688, 1.399, 1.299, -1.741, 0.754, -0.677, 0.037, P>0.05). During the first and second 24 h post injury, the urine volume and cumulative ratio of input to output volume of patients in inhalation injury group were respectively significantly lower and higher than those in non-inhalation injury group ( turine volume=2.421, 2.876, tcumulative ratio of input to output volume=-2.687、-2.943, P<0.05 or P<0.01). At PIH 72, the heart rate and HCT of patients in inhalation injury group ( (114±13) times/min, 0.42±0.06) were significantly higher than those in non-inhalation injury group ( (98±18) times/min, 0.38±0.06, t=-3.182, -2.123, P<0.05 or P<0.01), there were no statistically significant differences in respiratory rate and MAP between the patients in two groups ( t=0.359, 1.722, P>0.05). During the third 24 h post injury, there were no statistically significant differences in urine volume and cumulative ratio of input to output volume between the patients in two groups ( t=1.664, -1.895, P>0.05). Conclusions:The presence of inhalation injury can lead to increased fluid requirement in massive burn patients during shock stage. An appropriate increase of fluid volume in the fluid resuscitation of burn patients combined with inhalation injury would be beneficial for maintaining ideal urine output.

Objective:To develop a wireless sensor module for wound temperature and pressure (hereinafter referred to as wireless sensor module), and to carry out related characteristic test and biosafety evaluation.Methods:(1) The structure and working mode of the wireless sensor module were designed. The temperature and humidity sensor welded at one end of the flexible cable and the pressure sensor were simultaneously connected with the printed circuit board, which was welded with the Bluetooth transmitter, microprocessor, and power interface to establish a wireless sensor module. A mobile data receiving application was developed and the monitoring values of the wireless sensor module exposed to the air were read through the Bluetooth function on the smart phone. (2) The temperature of a 35-42 ℃ hot water bag was measured by the wireless sensor module and an infrared thermometer at the same time, and 30 pairs of data were compared with correlation analysis performed. (3) The vacuum sealing drainage material was pasted on the arm of the second author, and the wireless sensor module was placed in the condition of negative pressure. The negative pressure values measured by the wireless sensor module and the negative pressure meter values were recorded at the same time, and 14 pairs of data were compared with correlation analysis performed. (4) The corresponding material extract was prepared by adding 1 mL normal saline per 3 square centimeters surface area of the pressure sensor or flexible cable with temperature and humidity sensor welded respectively. Twenty 6-8 week-old female C57BL/6 mice were weighed before experiment and divided into pressure sensor extract group, flexible cable extract group, mixed extract group, and normal saline group according to the random number table ( n=5). The abnormal toxic reactions of mice were observed after intraperitoneal injection of pressure sensor extract, flexible cable with temperature and humidity sensor welded extract, 1∶1 mixed extract of pressure sensor extract and flexible cable with temperature and humidity sensor welded extract, and normal saline for 50 mL/kg in corresponding groups. The body mass of mice was weighed at 24, 48, and 72 hours after injection, and the toxicity of the materials was evaluated comprehensively. (5) Four Japanese big ear white rabbits aged 3-6 months were selected, and there was no limit between male and female. Two regions on the left side of the spine were applied with aseptic gauze as aseptic gauze group, and two areas on the right side of the spine were applied with wireless sensor module as wireless sensor module group. The skin status of each region was evaluated at 1, 12, 24, 48 hours after application, and the score according to the skin irritation score standard was recorded. (6) The corresponding material extract was prepared by adding 1 mL serum-free Dulbecco′s modification of Eagle′s medium (DMEM) per 1 square centimeter surface area of the pressure sensor or flexible cable with temperature and humidity sensor welded respectively. L-929 fibroblasts were divided into pressure sensor extract group, flexible cable extract group, phenol control group, and medium control group. The corresponding extract was added in the first two groups, the phenol control group was added with 64 g/L phenol, and the medium control group was cultured with serum-free DMEM. The total volumes of the above four groups were all 100 μL. The absorbance values on the 2nd, 4th, 7th day of culture were detected by methyl thiazolyl tetrazolium method to calculate the cell proliferation rate ( n=6 at each time point) and to grade the cytotoxicity. Data were statistically analyzed with paired samples t test, Wilcoxon signed rank test, Pearson correlation analysis, Spearman correlation analysis, Mann-Whitney U test, analysis of variance for repeated measurement, analysis of variance for factorial design, one-way analysis of variance, and Bonferroni correction. Results:(1) The smart phone successfully received the air temperature, humidity, and pressure information detected by the wireless sensor module through the Bluetooth function. (2) The temperature of the hot water bag measured by the wireless sensor module was (37.7±1.7) ℃, which was close to (37.7±1.7) ℃ of the infrared thermometer ( t=-0.112, P>0.05), and there was a significant positive correlation between them ( r=0.996, P<0.01). (3) The negative pressure of arm under negative pressure material measured by the wireless sensor module was -36.7 (-38.8, -27.4) kPa, which was significantly lower than -22.7 (-32.7, -12.5) kPa of negative pressure meter ( Z=-3.235, P<0.01), but there was a significant positive correlation between their absolute values ( ρ=1.000, P<0.01). (4) There was no abnormal toxic reaction in all groups of rats, and there was no statistically significant difference in body mass among the four groups of mice ( F=3.132, P>0.05). (5) The scores of skin irritation in application region of rats in the two groups were similar at 1, 12, 24, 48 hours after application ( Z=-1.000, <0.001, -0.620, <0.001, P>0.05). (6) At each time point of culture, compared with that of medium control group, the cell proliferation rate increased significantly in pressure sensor extract group and flexible cable extract group ( P<0.01) but decreased significantly in phenol control group ( P<0.01). On the 2nd, 4th, 7th day of culture, the cytotoxicity grade of phenol control group was 1, 1, and 2 respectively, and the cytotoxicity grade of each extract group was 0. Conclusions:The wireless sensor module integrates temperature, humidity, and pressure sensors, which can monitor local temperature and pressure and realize the visualization of parameters on the mobile application program. The measurement of temperature is accurate and the pressure measurement results are consistent with the values of the negative pressure meter with good biosafety. It possesses a big value in clinical application and prospects for development.

OBJECTIVE： To study improvement effects of ethanol extract from Taxillus sutchuenensis on blood glucose level， liver and renal complications in type 2 diabetes mellitus （T2DM） model mice and its mechanism. METHODS： T2DM model was established by high-glucose and high-fat feed combined with intraperitoneal injection of streptozotocin. Totally 60 T2DM model mice were randomly divided into model control group （normal saline）， positive control group [metformin， 150 mg/（kg·d）] and T. sutchuenensis ethanol extract high-dose， medium-dose and low-dose groups [30， 15， 7.5 g/（kg·d）， by crude drug]， with 12 mice in each group. Other 12 normal mice were included in blank control group （normal saline）. After given drug solution or normal saline for consecutive 28 d， the serum levels of FBG， FINS， IL-2， IL-4， IL-12， IFN-γ， Scr， BUN， ALT and AST were detected； 24 h urine was collected to detect the Ucr levels. The insulin sensitivity index （ISI） and insulin resistance index （HOMA-IR） were calculated. HE staining was used to observe the pathological change of hepatocytes. The levels of Bcl-2 and Bax in liver tissue as well as the levels of TLR4 and NF-κB p65 in renal tissue were detected. RESULTS： Compared with blank control group， the serum levels of FBG， FINS， IL-4， ALT， AST， BUN， Scr and HOMA-IR value were increased significantly in model control group， while the levels of Ucr， IL-2， IL-12， IFN-γ and ISI value were decreased significantly （P＜0.01）. The hepatocytes showed obvious pathological changes. Bcl-2 level and Bcl-2/Bax of liver tissue were decreased significantly， while Bax level was increased significantly （P＜0.01）. The levels of TLR4 and NF-κB p65 in renal tissue were increased significantly （P＜0.01）. Compared with model control group， histopathological changes of liver were relieved significantly in T. sutchuenensis ethanol extract groups. Except that there was no significant difference in serum level of IFN-γ and level of NF-κB p65 in renal tissue in T. sutchuenensis ethanol extract low-dose group， other indexes were improved significantly （P＜0.01 or P＜0.05）. CONCLUSIONS： T. sutchuenensis ethanol extract can improve high blood glucose， liver and renal complications， and protect liver and renal function in T2DM model mice. The mechanism may be associated with improving immunofunction， up-regulating anti-apoptosis factors， down-regulating the expression of apoptosis-promoting and inflammation- promoting factors so as to maintain the functional status of hepatocytes and reduce the degree of renal cell damage.

Smart dressings, which show obvious advantage and potential in wound treatment and real-time monitoring, attract widespread attention in recent years. Real-time and dynamic acquiring wound information is vital to the treatment and prognosis of wound. Further research on smart dressings is helpful for wound management, personalized treatment, and realization of medical application translation of health monitoring technology. In the article, we categorize smart dressings and conclude their functions according to the type of micro-environment information of wound gathered by smart dressings.

The correct differentiation of oligodendrocyte precursor cells (OPCs) is essential for the myelination and remyelination processes in the central nervous system. Determining the regulatory mechanism is fundamental to the treatment of demyelinating diseases. By analyzing the RNA sequencing data of different neural cells, we found that cyclin-dependent kinase 18 (CDK18) is exclusively expressed in oligodendrocytes. In vivo studies showed that the expression level of CDK18 gradually increased along with myelin formation during development and in the remyelination phase in a lysophosphatidylcholine-induced demyelination model, and was distinctively highly expressed in oligodendrocytes. In vitro overexpression and interference experiments revealed that CDK18 directly promotes the differentiation of OPCs, without affecting their proliferation or apoptosis. Mechanistically, CDK18 activated the RAS/mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase pathway, thus promoting OPC differentiation. The results of the present study suggest that CDK18 is a promising cell-type specific target to treat demyelinating disease.

Objective To investigate the bacterial resistance profile of clinical isolates collected in Tongling area . Methods Antimicrobial susceptibility test was conducted by Kirby‐Bauer method . All the data were analyzed with WHONET 5 .6 software .Results A total of 3 419 clinical isolates were collected during 2013 ,of which gram negative organisms and gram positive organisms accounted for 75 .9% and 24 .1% .MRSA accounted for 41 .3% of S .aureus and MRCNS accounted for 73 .5% of coagulase negative Staphylococcus ,respectively .MRSA showed higher resistance to gentamicin ,ciprofloxacin , erythromycin and rifampicin . No vancomycin‐ or teicoplanin‐resistant strains of Staphylococcus spp . were found . No vancomycin‐or teicoplanin‐resistant strains of E . f aecalis and E . f aecium were found .About 51 .6% of E .coli isolates and 42 .8% of K . pneumoniae isolates produced extended‐spectrum β‐lactamases (ESBLs ) . The prevalence of imipenem‐ or meropenem‐resistant strains of K . pneumoniae increased significantly .The percentage of P . aeruginosa strains resistant to amikacin ,piperacillin‐tazobactam ,ciprofloxacin ,cefepime and cefoperazone‐sulbactam was lower than 20 .0% .The percentage of A .baumannii strains resistant to cefoperazone‐sulbactam , minocycline and amikacin w as 34 .7% ,57 .0% and 58 .3% , respectively . More than 68 .0 % of A . baumannii strains were resistant to any of the other antibiotics tested . Conclusions The antibiotic resistance is growing in clinical bacterial isolates .The spread of carbapenem‐resistant strains of K . pneumoniae in some departments poses a serious threat to clinical practice .We should pay more attention to resistance surveillance and rational use of antibiotics .

Patients diagnosed to have acute coronary syndromes( ACS) were included in the study. All ACS patients were divided into non-diabetes group(40 cases) and diabetes group(80 cases) . Blood coagulation function was de-termined for all patients. In the diabetes group eighty patients were randomly divided into ticagrelor group (48 ca-ses) and clopidogrel group (32 cases) . After 5 days′treatment, platelet function was detected. Our study aimed to examine the effects of ticagrelor and clopidogrel on the platelet function.

Objective To investigate the bacterial resistance of clinical isolates collected in Tongling area. Methods Antimicrobial susceptibility test was conducted by Kirby-Bauer method.All the data were analyzed with WHONET 5.5 software.Results A total of 3 092 clinical isolates were collected during 2012,of which gram negative organisms and gram positive organisms accounted for 76.3% (2 359/3 092)and 23.7% (773/3 092),respectively.MRSA and MRCNS accounted for 50.9% of S.aureus and 73.0% of coagulase negative Staphylococcus,respectively.MRSA and MRCNS showed higher resistance to gentamicin,ciprofloxacin and erythromycin.No vancomycin-or teicoplanin-resistant strains of Staphylococcus spp.were found.No vancomycin-or teicoplanin-resistant strains of E.faecalis were found.Some E.faecium strains were resistant to vancomycin and teicoplanin.About 52.1% of E.coli isolates and 42.1% of Klebsiella isolates produced extended-spectrumβ-lactamases (ESBLs).Imipenem-or meropenem-resistant strains of K. pneumoniae were found. The percentage of P.aeruginosa strains resistant to amikacin, cefoperazone-sulbactam and cefepime was 3.4%,14.0% and 17.7%,respectively.More than 70% of Acinetobacter spp. strains were resistant to all the antibiotics tested except minocycline and cefoperazone-sulbactam,to which 42.1%and 4.4% of the strains were resistant.Conclusions The antibiotic resistance of clinical bacterial isolates is growing. The spread of multi-drug or pan-drug resistant strains in a specific region poses a serious threat to clinical practice.We should pay more attention to resistance surveillance and the rational use of antibiotics.