Magnesium-doped calcium silicate(CS)bioceramic scaffolds have unique advantages in mandibular defect repair;however,they lack antibacterial properties to cope with the complex oral microbiome.Herein,for the first time,the CS scaffold was functionally modified with a novel copper-containing polydopamine(PDA(Cu2+))rapid deposition method,to construct internally modified(*P),externally modified(@PDA),and dually modified(*P@PDA)scaffolds.The morphology,degradation behavior,and mechanical properties of the obtained scaffolds were evaluated in vitro.The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance.During the prolonged immersion stage,the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release.The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA,while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects.Finally,the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model.Overall,it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+)modification,and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

ObjectiveTo construct a quantitative prediction model of three indicators（moisture absorption rate， film thickness and coating weight gain） during the coating process of Vitamin C Yinqiao tablets（VCYT） by near-infrared spectroscopy（NIRS）， and to realize the endpoint judgment. MethodReal-time NIRS data of 4 batches of VCYT during the coating process were collected by diffuse reflection method. The coating method employed was the rolling coating method， and the samples were obtained at the spray stage from the coater's sampling port every 10 minutes， and 57 batches of samples（about 1 800 tablets） were collected at various coating times， the tablets were embedded in molten paraffin， cut longitudinally， and observed by stereomicroscope. The film thickness， with a target value of 38 μm， was then measured using Motic Images Advanced 3.2 software. Furthermore， the mositure absorption rate of samples， aiming for a target value of 3%， was determined in accordance with guiding principles for drug hygroscopicity testing in the 2020 edition of Chinese Pharmacopoeia， and 3 samples were randomly selected from each batch（10 tablets per batch）， and the coating weight gain was calculated（target value of 4%）. Partial least squares regression（PLSR） was used to construct a quantitative model of the 3 coating indicators， and the predicted values of the coating indicators were smoothed using the moving average method and used to determine the coating endpoints. ResultThe prediction determination coefficients（R_p²） for moisture absorption rate， film thickness and coating weight gain were 0.933 4， 0.932 6 and 0.965 9， the root mean square errors of prediction（RMSEP） were 0.163 5%， 1.870 9 μm and 0.240 3%， the relative percent deviations（RPD） were 3.711 0， 2.760 7 and 5.415 8， respectively. The results of the external validation set demonstrated that the real-time predicted values obtained by the models exhibited the same trend as the measured values， and the coating endpoint could be accurately predicted（with a prediction error of less than 7.32 min and a relative error of less than 5.63%）. ConclusionThe established NIRS model exhibits excellent predictive performance and can be used for quality control of VCYT during the coating process.

Objective:To study the changes of early (i.e., within post injury day (PID) 14) coagulation function in patients with severe burns.Methods:A retrospective case series study was conducted. From December 2018 to December 2019, 50 severe burn patients who met the inclusion criteria were admitted to Guangzhou Red Cross Hospital of Jinan University. According to the severity of burns, the patients were divided into severe burn group (17 cases, including 12 males and 5 females) and extremely severe burn group (33 cases, including 26 males and 7 females). The platelet count (PLT), and conventional coagulation indexe and thromboelastogram index levels of patients were collected at admission, post injury hour (PIH) 48 and 72, and on PID 7 and 14. The conventional coagulation indexes included prothrombin time (PT), thrombin time (TT), activated partial prothrombin time (APTT), and fibrinogen (FIB) and D-dimer levels. The thromboelastogram indexes included coagulation angle (i.e., α angle), coagulation composite index (CI), MA value, R value, and K value (reflecting maximum amplitude, coagulation reaction time, and blood agglutination time, respectively). Data were statistically analyzed with independent sample t-test, Wilcoxon rank sum test, and chi-square test. Verification of the mixed effect model was performed on each index data of patients in the two groups, while the repeated measures analysis of variance was performed on PLT. Pearson correlation analysis or Spearman correlation analysis were performed to analyze the correlation between the thromboelastogram index data (except CI) and the PLT and conventional coagulation index data, respectively. Results:At admission, PIH 48 and 72, and on PID 7 and 14, PLT of patients in severe burn group were (203±91), (148±70), (123±63), (203±62), (402±140)×10 9/L, respectively, PLT of patients in extremely severe burn group were (235±116), (145±71), (109±52), (235±106), (455±138)×10 9/L, respectively. In overall comparison, only the difference of the main effect of time factor was statistically significant ( F=92.55, P<0.05). In severe burn group, statistically significant differences were only identified in comparison of patients' PLT between PID 7 and the adjacent two time points (at PIH 72 and on PID 14, with both P values <0.05). The differences in PLT of patients between all the adjacent time points in extremely severe burn group were statistically significant ( P<0.05). In the overall comparison of PT, TT, and FIB level of patients in the two groups at each time point, only the difference of main effect of time factor was statistically significant (with F values of 6.04, 8.45, and 32.90, respectively, all P values <0.05), and APTT and FIB level of patients in extremely severe burn group within PID 14 were higher than those in severe burn group. There were statistically significant differences in MA value, α angle, K value, and CI of patients in the two groups at each time point (with F values of 18.82, 11.38, 9.11, and 9.42, respectively, all P values <0.05). MA value was moderately correlated with PLT ( r=0.69, P<0.05), weakly correlated with TT and FIB level (with r values of -0.29 and 0.30 respectively, P<0.05), and very weakly correlated with D-dimer level ( r=-0.15, P<0.05); α angle was moderately correlated with PLT ( r=0.58, P<0.05), and weakly correlated with FIB level and TT (with r values of 0.26 and -0.29, respectively, P<0.05); R value was weakly correlated with APTT and FIB level (with r values of 0.24 and 0.31, respectively, P<0.05), and very weakly correlated with PT and TT (with r values of 0.16 and 0.14, respectively, P<0.05); K value was moderately correlated with PLT ( r=-0.59, P<0.05), and weakly correlated with FIB and TT (with r values of -0.29 and 0.32, respectively, P<0.05), and very weakly correlated with D-dimer level ( r=-0.15, P<0.05). Conclusions:Severe burn patients are already characterized with coagulation function changes in early stage, including insufficiency of coagulation function, enhanced platelet aggregation ability and enhanced FIB function. There is a certain correlation between conventional coagulation indexes and thromboelastogram indexes, but they cannot replace each other.

Objective:To evaluate the systemic absorption and safety of multiple doses of topical tazarotene/betamethasone dipropionate cream in healthy subjects and patients with psoriasis.Methods:From September 2008 to April 2009, 12 healthy subjects collected from Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College were randomly and equally divided into tazarotene 0.15%/betamethasone dipropionate 0.15% cream group and tazarotene 0.2%/betamethasone dipropionate 0.2% cream group; these subjects were instructed to apply 0.03 g of the test drug per day on each of the 4 body sites, including the flexor aspects of bilateral forearms, waist and back, for 7 consecutive days, and venous blood samples were obtained before, and 1, 3, 5 and 7 days after the start of drug application. From October 2010 to August 2011, 60 patients with non-cephalic psoriasis collected from the Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College were randomly divided into 3 groups at a ratio of 3∶1∶1, i.e., tazarotene 0.05%/betamethasone dipropionate 0.05% cream group ( n = 36) and tazarotene 0.05% gel group ( n = 12) topically treated with a cream vehicle in the morning and the test drug at night, and betamethasone dipropionate 0.05% cream group ( n = 12) topically treated with the test drug twice a day (once in the morning and again in the evening) ; the treatment lasted 6 consecutive weeks, and venous blood samples were collected before, and 2, 4 and 6 weeks after drug application. Liquid chromatography-tandem mass spectrometry was performed to determine the concentrations of tazarotenic acid and betamethasone in plasma. During the trial, adverse events in the subjects were recorded, routine blood and urine examinations were carried out, and liver and kidney function were evaluated before and after treatment. Results:The plasma concentrations of tazarotenic acid and betamethasone in the 12 healthy subjects were below the lower limit of quantitation (0.04 μg/L) after 1-, 3-, 5- and 7-day treatment. After the consecutive treatment, tazarotenic acid and betamethasone were detected in 2 (5.56%) and 4 (11.11%) patients respectively at week 2, 4 or 6 in the tazarotene 0.05%/betamethasone dipropionate 0.05% cream group, and the highest plasma concentrations of tazarotenic acid and betamethasone were 0.112 and 0.201 μg/L respectively; in the betamethasone dipropionate 0.05% cream group, betamethasone was detected in 2 of 12 patients, and the highest plasma concentration of betamethasone was 0.112 μg/L. No test drug-related systemic adverse reactions or laboratory abnormalities were observed in any of the healthy subjects or patients.Conclusion:Multiple doses of topical tazarotene/betamethasone dipropionate cream has advantages of little systemic absorption, no long-term accumulation and good systemic safety.

Objective: To analyze the causes of complication of early acute kidney injury (AKI) in four severely burned patients, and to explore the related treatment methods. Methods: The clinical data of 4 patients with severe burn complicated with early AKI admitted to Guangzhou Red Cross Hospital Affiliated to Medical College of Jinan University (hereinafter referred to as our hospital) from June 2014 to December 2017 were retrospectively analyzed. All the patients were male, aged 23-33 (30±5) years old, with depth of burns ranged from deep partial-thickness to full-thickness, complicated with myofascial compartment syndrome of extremities and varying degrees of striated muscle injury, and treated in other hospitals before transfer to our hospital. The patients were numbered from small to large according to the total burn area. The total burn area of patients No. 1, 2, 3, and 4 was 10%, 80%, 90%, and 95% total body surface area respectively, their occurrence time of early AKI was 48, 11, 29, and 48 hours after injury respectively, and their time of arriving our hospital was 60, 11, 29, and 144 hours after injury respectively. Hypovolemic shock occurred in patients No. 2 and 3 at admission to our hospital. All the patients received continuous renal replacement therapy (CRRT) after admission to our hospital. Under the support of hemodynamic monitoring and organ function monitoring, the limbs complicated with myofascial compartment syndrome were incised, thorough decompression exploration was performed, and necrotic muscle tissue was removed or amputation was performed. After escharectomy and decompression of limbs, fresh granulation wounds were formed by temporarily covering wounds with Jieya dressing skin or pig skin, multiple debridements, and vacuum sealing drainage. Fresh granulation wounds and other wounds underwent staged eschar excision and shaving were covered with autologous Meek skin graft, particulate skin graft, reticular skin graft and small skin graft respectively. The treatment outcome, CRRT time, operation times, time of recovery of serum creatinine and myoglobin, length of hospital stay, and follow-up were recorded. Results: All the 4 patients were cured after transfer to our hospital. Among them, totally 5 limbs of patients No. 1 and No. 4 underwent amputation because of complication of myofascial compartment syndrome and a large amount of necrotic muscle which could not be preserved. Patients No. 1, 2, 3, and 4 were treated with CRRT for 19, 35, 14, and 25 days respectively and performed with operation for 5, 6, 10, 8 times respectively. Serum creatinine of patients No. 1, 2, 3, and 4 returned to normal on 22, 35, 37, and 48 days after transfer respectively, and their serum myoglobin returned to normal on 18, 28, 25, and 30 days after transfer respectively. Patients No. 1, 2, 3, and 4 were hospitalized for 52, 105, 148, and 156 days and discharged after basic wound healing. Follow-up for 1 to 36 months showed no abnormal renal function in 4 patients. Conclusions The early AKI in patients No. 1 and 4 was caused by rhabdomyolysis after severe burn complicated with myofascial compartment syndrome, while that of the other 2 cases were also related to hypovolemic shock and poor renal perfusion. The success rate of early AKI treatment in severely burned patients can be effectively improved by removing the causes of diseases at the same time of CRRT and actively treating burn wounds under the support of organ function and hemodynamic monitoring.

Objective    To detect the difference of periostin expression in small cell lung cancer (SCLC) cell, and explore its effect on chemoresistance of SCLC patients. Methods    The expression of periostin in mRNA and protein was detected by RT-PCR and Western blot analysis in SCLC H69 and multidrug resistant strain H69AR. The expression of periostin was up-regulated by recombinant plasmid-periostin in H69 cell. The survival rate in the transfected group was different from that of the negative control group and uninterrupted group. Results    The expression of periostin mRNA and protein in the sensitive strain H69 was lower than that of the multidrug resistant strain H69AR (P<0.05). The recombinant periostin-plasmid was transfected into H69 cells and at the same concentration of chemotherapeutic drugs (cisplatin, etoposide) the survival rate increased significantly (P<0.05). The positive expression rate of periostin in SCLC tissues was 67.44%, and the sensitivity of the chemotherapy group was lower than that of the drug resistant group (P<0.05). Conclusion    The expression of periostin in SCLC cell H69 is significantly lower than that of the multidrug resistant strain H69AR and overexpression of periostin increases resistance of the sensitive strain H69 and hence periostin may be involved in SCLC chemoresistance.

Objective To analyze the motivation of Chinese patients with chronic myelogenous leukemia (CML) who have stopped the tyrosine kinase inhibitor (TKI). Methods Forty-seven CML patients who have stopped TKI provided informed consent prior to their participation in the study. These patients were divided into relapse and non-relapse group at the endpoint of the observation. None of the patients received any CML-associated therapies after TKI cessation. The reasons of withdrawal were analyzed statistically. Results The reasons for cessation included patient's request due to cost(59.57 %, 28/47), patient's plan to getting pregnant(8.52 %,4/47),side-effect of TKI(23.40 %,11/47)and other reasons(8.52 %,4/47).At the endpoint of observation, 23 patients suffered molecular relapse. Among them, 15 cases (65.22 %) were due to cost; 1 case (4.35 %) was due to getting pregnant, 5 cases (21.74 %) were due to side-effect and 2 cases (8.69 %) were due to other reasons. There was more frequency relapse in the group of insufficient cost. Conclusion The motivation of Chinese CML patients who have stopped TKI might show impact on the outcome,and the motivation is mainly related with history of drug reduction and withdrawal.

OBJECTIVETo investigate the effects of unified surgical scheme for wounds on the outcome of patients with extensive deep partial-thickness to full-thickness (briefly referred to as deep) burn.

METHODSOne hundred and thirty-seven patients with extensive deep burn hospitalized from July 2007 to November 2012 underwent unified surgery according to area of deep wound (unified scheme group, US). Among them, 57 patients with deep wound area less than 51% TBSA received escharectomy or tangential excision by stages followed by autologous mesh skin grafting; 52 patients with deep wound area from 51% to 80% TBSA underwent escharectomy or tangential excision by stages followed by autologous mesh skin grafting and/or small skin grafting, or escharectomy or tangential excision followed by large sheet of allogeneic skin covering plus autologous mesh skin grafting and/or small skin grafting after the removal of allogeneic skin; 28 patients with deep wound area larger than 80% TBSA received escharectomy or tangential excision by stages followed by autologous microskin grafting plus coverage of large sheet of allogeneic skin, or escharectomy or tangential excision followed by small autologous skin grafting and/or intermingled grafting with small autologous and/or allogeneic skin. Another 120 patients with extensive deep burn hospitalized from January 2002 to June 2007 who did not receive unified surgical scheme were included as control group (C). Except for the surgical methods in group US, in 53 patients with deep wound area less than 51% TBSA in group C escharectomy or tangential excision was performed followed by autologous small skin grafting; in 40 patients with deep wound area from 51% to 80% TBSA in group C escharectomy or tangential excision was performed followed by autologous microskin grafting plus large sheet of allogeneic skin covering, or escharectomy or tangential excision followed by large sheet of allogeneic skin embedded with stamp-like autologous skin; in 27 patients with deep wound area larger than 80% TBSA in group C escharectomy or tangential excision was performed followed by covering with large sheet of allogeneic skin embedded with stamp-like autologous skin without intermingled grafting with small autologous and allogeneic skin in group US. In group US, escharectomy of full-thickness wound in extremities was performed with the use of tourniquet in every patient; saline containing adrenaline was subcutaneously injected when performing escharectomy or tangential excision over the trunk and skin excision; normal skin and healed superficial-thickness wound were used as donor sites for several times of skin excision. The baseline condition of patients and their treatment in the aspects of fluid resuscitation, nutrition support, anti-inflammation, and organ function support were similar between the two groups. The mortality and incidence of complications of all patients and wound healing time and times of surgery of healed patients were compared between the two groups. Data were processed with independent sample t test, Mann-Whitney U test, and Fisher's exact test.

RESULTS(1) Both the mortality and the incidence of complications of patients with deep wound area less than 51% TBSA in group US were 0, which were close to those of group C (with P values above 0.05). The number of times of surgery of healed patients with deep wound area less than 51% TBSA in group US was 2.4 ± 0.9, which was obviously fewer than that of group C (3.5 ± 1.8, U=-5.085, P<0.001), but with wound healing time close to that of group C (U=-1.480, P>0.05). (2) Both the mortality and the incidence of complications of patients with deep wound area from 51% to 80% TBSA in group US were 0, which were significantly lower than those of group C [both as 20.0% (8/40), with P values below 0.01]. The number of times of surgery and wound healing time of healed patients with deep wound area from 51% to 80% TBSA in group US were respectively 3.0 ± 1.0 and (43 ± 13) d, which were obviously fewer or shorter than those in group C [4.2 ± 2.3 and (61 ± 34) d, with U values respectively -2.491 and -2.186, P values below 0.05]. (3) Both the mortality and the incidence of complications of patients with deep wound area larger than 80% TBSA in group US were 25.0% (7/28), which were close to those of group C [both as 25.9% (7/27), with P values above 0.05]. The number of times of surgery and wound healing time of healed patients with deep wound area larger than 80% TBSA in group US were close to those of group C (with U values respectively -0.276 and -0.369, P values above 0.05).

CONCLUSIONSUnified surgical scheme can indirectly decrease the mortality and the incidence of complications of burn patients with deep wound area from 51% to 80% TBSA; it can reduce times of surgery of healed patients of this type and shorten their wound healing time.

Burns ; surgery ; Debridement ; methods ; Extremities ; Humans ; Severity of Illness Index ; Skin ; pathology ; Skin Transplantation ; Transplantation, Autologous ; Treatment Outcome ; Wound Healing

OBJECTIVETo analyze the detection, drug resistance, and status of infection of Acinetobacter baumannii (AB) in burn ICU during 3 years.

METHODSA total of 2 010 specimens of wound secretion, blood, venous catheter attachment, sputum, stool and urine were collected from 505 burn patients hospitalized in our burn ICU from January 2011 to December 2013, and bacterial culture was performed. Pathogens were identified by automatic microorganism identifying and drug sensitivity analyzer. Drug resistance of all the obtained AB to 16 antibiotics commonly used in clinic, including cefoperazone/sulbactam, polymyxin, etc., was tested with K-B paper disk diffusion method. Patients with AB infection were ascertained. The WHONET 5.6 software was used to analyze the distribution of pathogens during 3 years, the isolation of AB with different sources and the status of drug resistance of AB to 16 antibiotics each year, and the status of patients with AB infection, and their outcome.

RESULTSA total of 961 strains of pathogens were isolated, among which 185 (19.25%) strains were Gram positive cocci, 728 (75.75%) strains were Gram negative bacilli, and 48 (4.99%) strains were fungi. A total of 172 strains of AB were isolated, ranking the second place among all the detected pathogens, with 67 (38.95%) strains from wound secretion, 11 (6.40%) strains from blood, 23 (13.37%) strains from venous catheter attachment, and 71 (41.28%) strains from sputum, no AB strain was isolated from feces or urine. The AB strains were found sensitive to polymyxin and with relatively low drug resistance rate to minocycline, while the drug resistance rates were over 80.0% to the other 14 antibiotics commonly used in clinic in 2013. AB culture of wound secretion was positive in 27 patients. Among them, 7 patients suffered from wound infection, and the wound infection was caused by AB in 1 out of the 7 patients. AB culture of blood was positive in 7 patients. Among them, 3 patients suffered from bloodstream infection, and the infection was due to AB invasion in 1 out of the 3 patients. AB culture of venous catheter attachment was positive in 20 patients. Among them, 8 patients suffered from bloodstream infection, and the infection was due to AB invasion in 1 out of the 8 patients. AB culture of sputum was positive in 35 patients. Among them, 13 patients suffered from ventilatory associated pneumonia, and 2 out of the 13 patients were diagnosed as AB infection. A total of 69 patients were AB culture positive, among them 64 patients were cured, 2 patients were transferred to other hospitals, and 3 patients died, with the mortality rate of 4.35%.

CONCLUSIONSAB in our burn ICU has a high detection rate and extensive drug resistance in above-mentioned 3 years. However, AB was mainly colonized in patients with extensive burns with a low mortality rate.

Acinetobacter Infections ; drug therapy ; epidemiology ; microbiology ; Acinetobacter baumannii ; drug effects ; isolation & purification ; Anti-Bacterial Agents ; pharmacology ; Burns ; microbiology ; Cross Infection ; Drug Resistance ; Gram-Negative Bacteria ; isolation & purification ; Humans ; Intensive Care Units ; Microbial Sensitivity Tests

A simple and rapid method was developed based on high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to determine sivelestat and its metabolite XW-IMP-A in human plasma. After a simple protein precipitation, the samples and internal standards were analyzed on a C18 column by a gradient elution program. The mobile phase consisted of 30% acetonitrile in methanol and 5 mmol · L(-1) ammonium acetate at a flow rate of 0.7 mL · min(-1). The mass spectrometric data was collected in multiple reaction monitoring mode (MRM) in the negative electrospray ionization. The standard curves were linear in the range of 10.0-15,000 ng · mL(-1) for sivelestat, and 2.50-1000 ng · mL(-1) for XW-IMP-A. The low limits of quantitation were identified at 10.0 and 2.50 ng · mL for sivelestat and XW-IMP-A, respectively. The intra- and inter-day precision were within 11.3% and 13.1% for sivelestat and XW-IMP-A, and accuracy was 0.3% and 0.6% for sivelestat and XW-IMP-A, within the acceptable limits across all concentrations. The method was successfully validated in the pharmacokinetic study of sivelestat in healthy Chinese volunteers.