[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective To explore whether dexmedetomidine(DEX)can alleviate exertional heatstroke(EHS)-induced rhabdomyolysis(RM)in rats by activating adrenergic α2 receptors,and to explore its potential mechanism based on the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/interleukin-1β(IL-1β)pathway.Methods Thirty-six male Sprague-Dawley(SD)rats,after a 7-day acclimatization training,were randomly divided into six groups:control group(CN group),EHS group,low-dose DEX group(EHS+low DEX group),high-dose DEX group(EHS+high DEX group),DEX combined with yohimbine(YOH)group(EHS+high DEX+YOH group),and YOH group(EHS+YOH),with six rats in each group.Before modeling,EHS+high DEX+YOH group and EHS+YOH group were intraperitoneally injected with YOH at 1 mg/kg,while the other four groups were injected intraperitoneally with an equal dose of physiological saline(0.9%NS).During modeling,except for CN group,the other 5 groups of rats were subjected to heat exercise in a high-temperature and high-humidity chamber to construct an EHS rat model.After successful modeling,EHS+low DEX group was intraperitoneally injected with DEX at 10 μg/kg,EHS+high DEX group and EHS+high DEX+YOH group were intraperitoneally injected with DEX at 30 μg/kg,and CN group,EHS group and DEX+YOH group were intraperitoneally injected with equal doses of saline.After 6 h of observation,all rats were anesthetized,and their blood from the abdominal aorta and gastrocnemius muscle tissue were taken.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of serum tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β and myoglobin(MB)in rats;biochemical assay kit was used to measure the level of creatine kinase(CK)in rat serum;HE staining was used to observe pathological changes in rat gastrocnemius muscle tissues;transmission electron microscopy was used to observe ultrastructural changes in gastrocnemius muscle;2′,7′-dichlorofluorescent yellow diacetate(DCFH-DA)fluorescent probe was used to detect the level of reactive oxygen species(ROS);and Western blotting was performed to detect the expression levels of NOD-like receptors 3(NLRP3),aspartic protease-1(caspase-1)and adrenergic α2A receptor(ADRA2A).Results Compared with CN group,the levels of serum IL-6,IL-1β,TNF-α,CK and MB in EHS group rats were significantly elevated(P<0.01).HE staining results revealed that the gastrocnemius muscle tissues of rats in EHS group had these pathological manifestations such as disarray of muscle fibrous structure,hemorrhage,edema,and infiltration of inflammatory cells.Transmission electron microscopy results showed that the ultrastructure of the gastrocnemius muscle in EHS group exhibited myofibroblasts with swelling and enlarging in size,cytoplasmic vacuolization,and mitochondria with obvious swelling,degranulation,and disappearance of double cristae.Compared with CN group,the expression levels of ROS,NLRP3,and caspase-1 in gastrocnemius of rats in EHS group significantly increased(P<0.01);Compared with EHS group,the levels of TNF-α,IL-6,IL-1β,CK,MB and the expression levels of ROS,NLRP3,caspase-1 in gastrocnemius tissue of rats in EHS+low DEX group and EHS+high DEX group decreased in a dose-dependent manner(P<0.05),and the pathological damage observed with HE staining and transmission electron microscopy was alleviated by DEX.After YOH pretreatment,compared with the EHS+high DEX group,the serum levels of TNF-α,IL-6,IL-1β,CK,MB and ROS,NLRP3 and caspase-1 in the gastrocnemius muscle tissue of rats in EHS+high DEX+YOH group relatively increased(P<0.05),and the pathological damage observed with HE staining and transmission electron microscopy was exacerbated.The expression of ADRA2A in gastrocnemius muscle of EHS group significantly decreased compared with CN group(P<0.01),and the expression of ADRA2A in muscle of rats in DES+low DEX group and EHS+high DEX group was higher than that in EHS group(P<0.05).Conclusions DEX can alleviate EHS-induced RM by activating ADRA2A,potentially through inhibiting the ROS-dependent NLRP3/IL-1β inflammatory pathway.

BACKGROUND:For the replacement treatment of long-segment tracheal defects,although tissue engineering research has made some progress in recent years,it is still not perfect,and one of the biggest difficulties is that the hemodynamic reconstruction of the tracheal replacement cannot be achieved rapidly. OBJECTIVE:To preliminarily explore the potential of polycaprolactone scaffolds modified with exosome-loaded hydrogels to construct a rapidly vascularized tracheal substitute. METHODS:Exosomes were extracted from bone marrow mesenchymal stem cells of SD rats.After preparation of hyaluronic acid methacrylate solution,the exosome solution was mixed with hyaluronic acid methacrylate solution at a volume ratio of 1:1.Hyaluronic acid methacrylate hydrogels loaded with exosomes were prepared under ultraviolet irradiation for 5 minutes.The degradation of exosome-unloaded hydrogels and the controlled release of exosome-loaded hydrogels were detected.Polycaprolactone scaffolds were prepared by 3D printing.The pure hyaluronic acid methacrylate solution and the exosome-loaded hyaluronic acid methacrylate solution were respectively added to the surface of the scaffold.Hydrogel-modified scaffolds and exosome-modified scaffolds were obtained after ultraviolet irradiation.Thirty SD rats were randomly divided into three groups with 10 rats in each group and subcutaneously implanted with simple scaffolds,hydrogel-modified scaffolds and exosome-modified scaffolds,respectively.At 30 days after surgery,the scaffolds and surrounding tissues of each group were removed.Neovascularization was observed by hematoxylin-eosin staining and Masson staining and the expression of CD31 was detected by immunofluorescence. RESULTS AND CONCLUSION:(1)As time went by,the hydrogel degraded gradually,and the exosomes enclosed in the hydrogel were gradually released,which could be sustained for more than 30 days.The exosome release rate was faster than the degradation rate of the hydrogel itself,and nearly 20%of the exosomes were still not released after 30 days of soaking.(2)Under a scanning electron microscope,the surface of the simple polycaprolactone scaffold was rough.After hydrogel modification,a layer of gel was covered between the pores of the scaffold,and the scaffold surface became smooth and dense.(3)After 30 days of subcutaneous embedding,hematoxylin-eosin staining and Masson staining showed that more neovascularization was observed inside the scaffolds of the exosome-modified scaffold group compared with the hydrogel-modified scaffold group.The hydrogels on the scaffolds of the two groups were not completely degraded.Immunofluorescence staining showed that CD31 expression in the exosome-modified scaffold group was higher than that in the hydrogel-modified scaffold group(P<0.000 1).(4)These results indicate that hyaluronic acid methacrylate hydrogels can be used as controlled-release carriers for exosomes.The 3D-printed polycaprolactone scaffold modified by hyaluronic acid methacrylate hydrogel loaded with exosomes has good biocompatibility and has the potential to promote the formation of neovascularization.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

AIM To investigate the protective effect of Mongolian medicine Naru-3 on rat rheumatoid arthritis(RA)using imaging method.METHODS With the rats divided into the normal group,the model group,the positive medicine group,and the low,medium and high dose Naru-3 groups(0.1,0.2 and 0.4 g/kg),the rat model of collagen-induced arthritis(CIA)was established by immune induction method.After 4 weeks of corresponding drug administration,the rats had their changes of arthritis index(AI)level and body weight observed;their serum levels of VEGF,TNF-α and IL-1 detected by ELISA;their synovial hyperplasia and neovascularization evaluated by high-frequency ultrasound and contrast-enhanced ultrasound(CEUS);their bone destruction of ankle joint evaluated by X-ray and high-resolution micro-CT;and their synovial membrane and expressions of CD31,VEGF,TNF-α and IL-1 β observed by HE and immunohistochemistry.RESULTS Compared with the model group,the Naru-3 groups displayed increased rat weight(P＜0.05);no significantly changed AI score(P＞0.05);and overally decreased levels of serum VEGF,TNF-α,synovial membrane thickness,blood flow signal by power Doppler imaging(PDI)and contrast intensity revealed,X-ray score,and CD31 expression(P＜0.05),in addition to the decreased level of IL-1 and HE score in high-dose group(P＜0.05).CONCLUSION Naru-3 is protective to the joint tissue in rat model of RA through alleviating synovitis,bone erosion and delaying the progress of the disease by inhibiting synovial neovascularization and inflammatory cytokines.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective: To explore the efficacy of immunosuppression intensified conditioning regimen in patients who have strongly positive donor-specific Anti-HLA antibodies (DSAs) and received a haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Clinical data of 10 patients with strongly positive pretransplant DSAs (defined as MFI ≥10000) were retrospectively analyzed in this study. All of them received a haplo-HSCT in the Hematology Department of Shanghai Zhaxin Traditional Chinese & Western Medicine Hospital. Results: ① Of all ten patients, three were males, and seven were females, with a median age of 53.5 (36-64) years. Of the 10 patients, three were diagnosed with acute myeloid leukemia, two were myelodysplastic syndromes (MDS), two were chronic myelomonocytic leukemia (CMML), two were in an accelerated phase of chronic myeloid leukemia (CML-AP), and one was primary myelofibrosis (PMF). ② Conditioning regimen consisted of fludarabine (Flu) /busulfan (Bu) combined with whole-body irradiation (TBI) /cyclophosphamide (Cy). ③ On the seventh day after transplantation, the median pretransplant DSA level was MFI 15 999 (10 210-23 417) and 10 787 (0-22 720). ④ Eight patients acquired hematopoietic reconstitution; the median time of neutrophil engraftment was 14 (10-16) days; and 18 (14-20) days for platelet engraftment. After a median follow-up of 12.5 (1.5-27) months, primary graft failure was found in one patient and another with poor graft function. Seven patients remained in a disease remission state, and all were DSA-negative. Conclusions: An intensified immunosuppression conditioning regimen can efficiently decrease the level of donor-specific anti-HLA antibodies (DSAs), leading to good short-term efficacy.
Male ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Graft vs Host Disease ; Transplantation Conditioning ; China ; Hematopoietic Stem Cell Transplantation ; Antilymphocyte Serum ; Busulfan ; Cyclophosphamide/therapeutic use* ; Immunosuppression Therapy

Humans ; Waldenstrom Macroglobulinemia ; Prospective Studies

Objective:To investigate the condylar resorption and influencing factors in post mandibular distraction osteogenesis of the hemifacial microsomia patients.Methods:This retrospective study investigated the clinical data of hemifacial microsomia patients who underwent mandibular distraction osteogenesis in the Department of Maxillofacial Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from October 2008 to August 2021. Three-dimensional models of pre-operation and pre-distractor extraction were created by the analysis of CT data via ProPlan CMF 3.0. The height and volume of the condyle were measured. Data were analyzed statistically. According to the changes of condylar height and volume pre- and post-operation, the condylar height resorption rate and volume resorption rate could be calculated. The volume resorption rate of the affected side between Type-Ⅱa and Type-Ⅱb hemifacial microsomia patients, hemifacial microsomia patients whether wearing a bite plate, prereproductive and adolescent hemifacial microsomia patients were compared with the Mann-Whitney U test. The Spearman correlation coefficient analysis was used to determine the correlations of the condylar volume resorption rate and condylar height resorption rate in the affected side with measurements of elogation distance, preoperative condylar height, patient age, and distractor remaining time in mandible. P<0.05 indicates that the difference was statistically significant. Results:Forty-seven Type-Ⅱa hemifacial microsomia patients(36 male patients, 11 female patients) were included, patient age ranged from 5 to 20 years and the mean age was (8.49±2.60) years, 36 patients were in the prereproductive age(5-<10 years old), and 11 patients were in the adolescent age(10-20 years old). Forty-six Type-Ⅱb hemifacial microsomia patients(34 male patients, 12 female patients) were included, patient age ranged from 5 to 20 years and the mean age was (8.93±3.43) years. Thirty-six patients were in the prereproductive age(5-<10 years-old), and ten patients were in the adolescent age(10-20 years-old). The follow-up period of Type-Ⅱa hemifacial microsomia patients was (8.49±2.60) months, and the follow-up period of Type-Ⅱb hemifacial microsomia patients was (9.79±2.59) months. Facial asymmetry was improved effectively. Surgical part of the bone had good osteogenesis. Mouth opening and closing, speech, and eating were all normal. The condylar volume resorption rate 34.8%(19.1%, 54.3%) in the affected side of Type-Ⅱa hemifacial microsomia was significantly associated with the elogation distance ( r=0.46, P=0.001), and it had no correlation with the height of the affected condyle ( r=-0.12, P=0.421), age of patients ( r=-0.06, P=0.691), and distractor remaining time in mandible ( r=-0.10, P=0.517). The condylar volume resorption rate 61.0%(11.2%, 95.0%) in the affected side of Type-Ⅱb hemifacial microsomia was significantly associated with the height of the affected condyle ( r=-0.45, P=0.002) and had weak correlation with the elogation distance ( r=0.29, P=0.049), and it had no correlation with age of patients ( r=0.06, P=0.705), and distractor remaining time in mandible ( r=0.21, P=0.157). However, there was no significant difference in terms of the condylar volume resorption rate of the affected side between Type-Ⅱa and Type-Ⅱb hemifacial microsomia ( z=-1.90, P=0.058). Whether the hemifacial microsomia patients wearing a bite plate following mandibular distraction osteogenesis did not affect the condylar volume resorption rate of the affected side ( z=-1.17, P=0.242 in Type-Ⅱa hemifacial microsomia, z=-0.17, P=0.869 in Type-Ⅱb hemifacial microsomia). The condylar volume resorption rate of the affected side had no significant difference between prereproductive and adolescent hemifacial microsomia patients ( z=-0.18, P=0.860 in Type Ⅱa hemifacial microsomia, z=-1.50, P=0.134 in Type-Ⅱb hemifacial microsomia). Conclusion:Condylar resorption of the affected side would happen in post mandibular distraction osteogenesis of the hemifacial microsomia patients, and the condylar resorption rate of the affected side has relationship with the elogation distance and affected preoperative condylar height.

Objective:To investigate the condylar resorption and influencing factors in post mandibular distraction osteogenesis of the hemifacial microsomia patients.Methods:This retrospective study investigated the clinical data of hemifacial microsomia patients who underwent mandibular distraction osteogenesis in the Department of Maxillofacial Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from October 2008 to August 2021. Three-dimensional models of pre-operation and pre-distractor extraction were created by the analysis of CT data via ProPlan CMF 3.0. The height and volume of the condyle were measured. Data were analyzed statistically. According to the changes of condylar height and volume pre- and post-operation, the condylar height resorption rate and volume resorption rate could be calculated. The volume resorption rate of the affected side between Type-Ⅱa and Type-Ⅱb hemifacial microsomia patients, hemifacial microsomia patients whether wearing a bite plate, prereproductive and adolescent hemifacial microsomia patients were compared with the Mann-Whitney U test. The Spearman correlation coefficient analysis was used to determine the correlations of the condylar volume resorption rate and condylar height resorption rate in the affected side with measurements of elogation distance, preoperative condylar height, patient age, and distractor remaining time in mandible. P<0.05 indicates that the difference was statistically significant. Results:Forty-seven Type-Ⅱa hemifacial microsomia patients(36 male patients, 11 female patients) were included, patient age ranged from 5 to 20 years and the mean age was (8.49±2.60) years, 36 patients were in the prereproductive age(5-<10 years old), and 11 patients were in the adolescent age(10-20 years old). Forty-six Type-Ⅱb hemifacial microsomia patients(34 male patients, 12 female patients) were included, patient age ranged from 5 to 20 years and the mean age was (8.93±3.43) years. Thirty-six patients were in the prereproductive age(5-<10 years-old), and ten patients were in the adolescent age(10-20 years-old). The follow-up period of Type-Ⅱa hemifacial microsomia patients was (8.49±2.60) months, and the follow-up period of Type-Ⅱb hemifacial microsomia patients was (9.79±2.59) months. Facial asymmetry was improved effectively. Surgical part of the bone had good osteogenesis. Mouth opening and closing, speech, and eating were all normal. The condylar volume resorption rate 34.8%(19.1%, 54.3%) in the affected side of Type-Ⅱa hemifacial microsomia was significantly associated with the elogation distance ( r=0.46, P=0.001), and it had no correlation with the height of the affected condyle ( r=-0.12, P=0.421), age of patients ( r=-0.06, P=0.691), and distractor remaining time in mandible ( r=-0.10, P=0.517). The condylar volume resorption rate 61.0%(11.2%, 95.0%) in the affected side of Type-Ⅱb hemifacial microsomia was significantly associated with the height of the affected condyle ( r=-0.45, P=0.002) and had weak correlation with the elogation distance ( r=0.29, P=0.049), and it had no correlation with age of patients ( r=0.06, P=0.705), and distractor remaining time in mandible ( r=0.21, P=0.157). However, there was no significant difference in terms of the condylar volume resorption rate of the affected side between Type-Ⅱa and Type-Ⅱb hemifacial microsomia ( z=-1.90, P=0.058). Whether the hemifacial microsomia patients wearing a bite plate following mandibular distraction osteogenesis did not affect the condylar volume resorption rate of the affected side ( z=-1.17, P=0.242 in Type-Ⅱa hemifacial microsomia, z=-0.17, P=0.869 in Type-Ⅱb hemifacial microsomia). The condylar volume resorption rate of the affected side had no significant difference between prereproductive and adolescent hemifacial microsomia patients ( z=-0.18, P=0.860 in Type Ⅱa hemifacial microsomia, z=-1.50, P=0.134 in Type-Ⅱb hemifacial microsomia). Conclusion:Condylar resorption of the affected side would happen in post mandibular distraction osteogenesis of the hemifacial microsomia patients, and the condylar resorption rate of the affected side has relationship with the elogation distance and affected preoperative condylar height.