Objective To determine the effects of~(99)Tc-MDP on joint inflammation and bone destruc- tion in collagen-induced arthritis(CIA)rats model and its effect on tumor necrosis factor alpha(TNF-?). Methods CIA was induced by immunization of male SD rats with an emulsion of collagen.~(99)Tc-MDP or placebo was intravenous infused to rats for 20 days.Joint inflammation was assessed by arthritis index.Lesions of bone were assessed based on the histological changes in ankle joints,radiographic analysis in hind paw with Larsen score.Systemic TNF-?level was measured by radioimmune assay.Results~(99)Tc-MDP suppressed joint swelling(P

OBJECTIVETo observe the functional changes of dendritic cells (DCs) after infection by recombinant retrovirus carrying human telomerase reverse transcriptase (hTERT) gene fragment.

METHODSInterleukin-12 (IL-12) levels in DC culture supernatant was determined by enzyme-linked immunosorbent assay (ELISA). The abilities of DCs infected with recombinant retrovirus carrying hTERT gene (hTERT-DCs) and non-infected DCs (N-DCs) to stimulate allogeneic lymphocyte proliferation were evaluated with mixed leukocytes reaction (MLR), and the surface markers of DCs including CD80, CD83, CD86 and HLA-DR were detected by flow cytometry. Cytotoxic T lymphocyte (CTL) assay was performed with CytoTox 96 non-radioactive cytoxicity assay.

RESULTSCompared with N-DCs, hTERT-DCs showed no significant changes in IL-12 secretion and capacity to stimulate allogeneic lymphocytes reaction, but had significantly lower CD83 expression. Specific CTLs induced by hTERT-DCs resulted in higher cytotoxicity against telomerase-positive target cells than that against the negative target cells.

CONCLUSIONInfection with the recombinant retrovirus carrying hTERT fragment may jeopardize the maturation of DCs, which, however, still retain their capacity to activate and stimulate lymphocyte proliferation and to prime autologous T lymphocytes to generate specific CTL against hTERT.

Cells, Cultured ; Dendritic Cells ; cytology ; immunology ; virology ; Genetic Vectors ; Humans ; Interleukin-12 ; biosynthesis ; Recombination, Genetic ; Retroviridae ; genetics ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology ; Telomerase ; biosynthesis ; genetics

Objective:To investigate the clinical characteristics of the disease spectrum of pediatric hyper blood immunoglobulin E (IgE).Methods:A total of 498 children with total serum IgE ≥ 5×10 5 IU/L admitted to the Department of Pediatrics, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University from January 2012 to December 2018 were enrolled.Their clinical data, etiology distribution, clinical manifestations, laboratory results, treatment and outcomes were retrospectively analyzed.According to serum total IgE level, patients were divided into mildly increased IgE group (5×10 5-<10×10 5 IU/L), moderately increased group (10×10 5-<20×10 5 IU/L), and severely increased group (≥20×10 5 IU/L). The distribution of disease types among the 3 groups were compared. Results:(1) Allergic disease (213 cases) was the most common etiology in children with hyper blood IgE, and infectious disease (163 cases), mycoplasma pneumoniae (109 cases) and EB virus (120 cases) were common pathogens.(2) The incidence of allergic diseases (45.0%) and infectious diseases (42.2%) in the mildly increased group was significantly higher than that in the moderately increased group (40.8%, 26.2%, respectively) and the severely increased group(38.9%, 12.2%, respectively) (all P<0.001). The incidence of immune diseases(18.5%), tumors and hematological diseases (5.4%) in the moderately increased group was significantly higher than that of the mildly increased group (4.4%, 2.0%, respectively) (all P<0.001). The incidence of immune diseases (34.4%), tumors and hematological diseases (11.1%) in the severely increased group was significantly higher than that of the mildly increased group(4.4%, 2.0%, respectively) and the moderately increased group (18.5%, 5.4%, respectively) (all P<0.001). (3) The main clinical manifestations were fever (63.5%), respiratory symptoms (53.7%) and lympha-denopathy (53.7%), 47.5% of the children with hyper blood IgE had an increased white blood cell count, and 12.1% of them had an increased eosinophil count.(4) The most common specific allergens were dust mite combination (32.0%), milk (17.0%), and egg white (16.0%). There was no difference in disease distribution among the 3 groups of hyper blood IgE children with positive specific IgE ( P=0.164). Conclusions:Hyper blood IgE in children are most commonly caused by allergic and infectious diseases.The etiological distributions of hyper blood IgE in children at varying severities differ a lot.The higher the total IgE level, the higher the incidence of immunodeficiency disease, rheumatic disease, tumor and hematological disease.

Objective To analyze the clinical manifestations and gene variations of tumor necrosis factor receptor-associated periodic syndrome (TRAPS).Methods Clinical data and gene testing of four children and three adult relatives in a family from Puning,Guangdong were retrospectively analyzed.CD4+T cells,CD8+T cells,B cells,monocytes and NK cells were assessed by flow cytometry.Plasma level of TNFR receptors were assessed by enzyme linked immunosorbent assay (ELISA).TNFRSF1A gene variation was identified by second generation sequencing.Swiss-Model was used to analyze the potential impact of TNFRSF1A gene variation on its protein tertiary structure.Results For all the patients,periodic fever was the main clinical feature,combined with arthralgia,myalgia,multiple serositis,periorbital edema and migratory cutaneous rash,accompanied with elevated level of acute-phase reactants and increased white blood cell counts during each episode.This disease was found in both gender and every generation in this family.The median age of onset was 2 years,ranging from 6 months to 30 years.The plasma level of TNFR1 of the patients range from 0 to 12.4 ng/L,which was lower than that of the normal controls range from 18.0～ 22.2 ng/L,while the level of TNFR2 was normal.Also,the numbers of T cells,B cells and monocytes were within normal range;however,number of NK cells in the patients (0.070±0.034) was lower than that in the normal controls (0.152±0.122).The TNFRSF 1A variation,located in exon 3:c.295T＞A (p.C99S),was found in the proband as well as the other 6 family members,which could induce change of the side chain of amino acid according to the prediction of the three-dimensional structure,subsequently affecting the binding to the receptor.Conclusions TRAPS is characterized by periodic fever,arthralgia,myalgia,multiple serositis,periorbital edema and migratory cutaneous rash,with a significant decrease in plasma level of TNFR1 and NK cells.The gene sequencing analysis revealed a pathogenic variation in TNFRSF1A gene.

Objective:To describe the current status of registration and design characteristics of clinical trials of new drugs for curing hepatitis B through domestic and foreign websites, so as to provide references for the follow-up clinical trials of new hepatitis B drugs.Methods:A search was conducted on the US Clinical Trials Database and the Chinese Clinical Trial Registry Center. The search date was from the establishment of the database to May 26, 2020, and the registration trials of new drugs for curing hepatitis B at home and abroad were included. Two researchers independently searched and screened the literature and extracted the data.Results:A total of 106 registered clinical trials of new drugs for curing hepatitis B were included (94 English registration websites and 12 Chinese registration websites), and the number of registrations had increased year by year. Among them, the proportion of therapeutic vaccines and core protein inhibitors were the highest, accounting for 27.4% ( n = 29) and 22.6% ( n = 24), respectively. The vast majority of clinical trials ( n = 96, 90.6%) were in the early stages (Phase I and II). The subjects in phase I clinical trial were mainly healthy people and treated CHB patients, while the subjects in phase II clinical trial were mainly CHB patients who had achieved viral suppression after initial or post-treatment. The main evaluation indicators of Phase I clinical trials were the safety and tolerability of new drugs. The main evaluation indicators in about half of Phase II clinical trials were HBsAg negative conversion/quantitative decline. Overall, the number of clinical trials with the new design was small, accounting for 3.8% (4 / 106). There were relatively few trials of new drugs for curing hepatitis B on domestic registration websites, and the information provided was incomplete. Conclusion:The number of clinical trials of new hepatitis B drugs at home and abroad is increasing year by year, but most of them are in phase I and II, with few adopting new designs. In addition, the information integrity of the domestic website registration center needs to be improved.

Objective: To investigate the clinical characteristics and risk factors of postoperative atrial fibrillation (POAF) in patients with critical burns. Methods: A retrospective case series study was conducted. From January 2017 to December 2021, two hundred and twenty-seven critically burned aldult patients who met the inclusion criteria were admitted to Guangzhou Red Cross Hospital of Jinan University, including 173 males and 54 females, aged 19-83 (43±14) years. The admission years of patients were collected, and the percentage of patients complicated with POAF in each year was calculated. According to whether the patients were complicated with POAF or not, they were divided into POAF group (n=17) and non-POAF group (n=210). Following data were collected in patients in POAF group, including operation methods, duration of operation, intraoperative blood loss before occurrence of POAF each time, occurrence time and times of POAF, postoperative body temperature, blood pressure, hemoglobin, blood glucose, blood lactate, sepsis, and electrolyte, and type, duration, and treatment of POAF. General data of patients in the two groups including age, gender, burn reason, total burn area, full-thickness burn area, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sepsis-related organ failure evaluation (SOFA) scores on admission, combined with underlying diseases (hypertension, diabetes, and other types of arrhythmias), and sepsis were collected and analyzed. The mortality and factors influencing the prognosis of patients in the two groups such as mechanical ventilation time, operations times, and burn intensive care unit (BICU) length of stay were also collected and analyzed. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test or Kruskal-Wallis H test. The multivariate logistic regression analysis was performed on the general data with statistically significant differences between the two groups, and the independent risk factors influencing the onset of POAF in 227 patients with critical burns were screened. Results: From 2017 to 2021, the percentage of critically burned patients complicated with POAF increased year by year. In POAF group, eschar debridement in limbs was the main surgical procedure prior to POAF complication, with the operation time of (3.5±1.2) h and the intraoperative blood loss volume of (365±148) mL.The POAF occurred 25 times in total in patients of POAF group, mostly within one week after the injury and within 6 hours after the operation with most of these patients having POAF only once. When POAF happened, the patients were often complicated with hypothermia, anemia, hyperglycemia, high blood lactate, sepsis, and electrolyte disturbance, and few patients had complications of hypotension. The POAF lasted (5±3) h, with all being paroxysmal atrial fibrillation, and most of POAF patients were reverted to sinus rhythm after amiodarone intervention. Most patients in the two groups suffered from flame burn, and the gender, age, and SOFA score on admission of patients in the two groups were similar (P>0.05); the APACHEⅡ score on admission, total burn area, full-thickness burn area, incidence proportion of sepsis, combined with diabetes and hypertension and other types of arrhythmias of patients in POAF group were significantly higher or larger than those in non-POAF group (t=3.47, with χ² values of 7.44, 10.86, 12.63, 14.65, 6.49, and 7.52, respectively, P<0.05 or P<0.01). The full-thickness burn area, combined with other types of arrhythmias, and sepsis were the independent risk factors for POAF in 227 critically burned patients (with odds ratios of 4.45, 0.04, and 3.06, respectively, with 95% confidence intervals of 2.23-8.87, 0.01-0.22, and 1.77-5.30, respectively, P<0.01). Compared with those in non-POAF group, the mechanical ventilation time, BICU length of stay, number of operations, and mortality rate of patients in POAF group were significantly increased (Z=3.89, Z=2.57, t=3.41, χ²=3.72, P<0.05 or P<0.01). Conclusions: POAF is a common postoperative complication in critically burned patients, and the incidence is increasing year by year, which seriously affects the prognosis of patients. The full-thickness burn area together with other types of arrhythmias and sepsis are the high-risk factors for POAF complication in patients with critical burns.
Atrial Fibrillation/etiology* ; Blood Loss, Surgical ; Female ; Humans ; Hypertension ; Lactates ; Male ; Prognosis ; Retrospective Studies ; Risk Factors ; Sepsis

Objective: To evaluate the model with spleen deficiency and dampness stagnancy by bioelectrical impedance analysis (BIA) and traditional indicators. Method: The forty rats were divided into blank group and model group, with 20 rats in each group. The rats in the blank group were fed with normal feed, the rats in model group were prepared with the spleen deficiency and dampness stagnancy model for 14 days. Observe the general condition of the rats, measure the water content of the feces in the dry method, measure the water load index by weighing method, and detect the urinary D-xylose excretion total protein (TP), albumin (Alb) content, by enzyme-linked immunosorbent assay (ELISA). Western blot analysis of renal aquaporin 1 (AQP1) content, and the use of experimental animal body composition analyzer to determine the total water content (TBW), extracellular fluid (ECF), intracellular fluid (ICF), fat mass (FM), free fat mass (FFM) and body mass bioelectrical impedance index such as body mass index (BMI). Result: Compared with blank group, the rats in model group lost weight, gradually loose stools occasionally, the anus temperature was basically unchanged, body mass, D-xylose excretion, water load index, TP and Alb content decreased (P<0.01). The feces contained water,the rate and the content of AQP1 in the renal pulp were increased (P<0.01). The TBW, ECF and FFM were increased, and the ICF, FM and BMI were decreased (P<0.01). Conclusion: Rats with spleen deficiency and dampness stagnancy induced a combination of factors such as diet and excessive fatigue. The bioelectrical impedance method can be more intuitive and comprehensive.

Objective To explore the obstacles in palliative care consultation services and put forward the suggestions for improving the services in grade A tertiary hospitals. Methods A semi-structured interview was conducted with 17 medical workers who had requested palliative care consultation services in Peking Union Medical College Hospital. Results The palliative care consultation services were hindered by five obstacle factors including insufficient knowledge of patients and their families about palliative care,unsound understanding of medical workers about palliative care,poor implementation of consultation opinions,limited labor of palliative care team,and poor economic benefits from palliative care.In view of such obstacles,the following suggestions were put forward,which included increasing the acceptance of palliative care by patients and their families,enriching the knowledge of medical staff on palliative care,establishing a new cooperation model between consultation team and medical staff,strengthening the institutional guarantee for the development of palliative care,and establishing and perfecting the laws and policies related to palliative care. Conclusion Although there are many difficulties in the in-hospital palliative care consultation services in grade A tertiary hospitals,the demand and expectation of medical staff for palliative care are still increasing.
Humans ; Palliative Care ; Tertiary Care Centers ; Referral and Consultation ; Hospitalization

Objective: To explore the effects and mechanism of water-soluble chitosan hydrogel on infected full-thickness skin defect wounds in diabetic mice. Methods: The experimental research method was adopted. The control hydrogel composed of polyvinyl alcohol and gelatin, and the water-soluble chitosan hydrogel composed of the aforementioned two materials and water-soluble chitosan were prepared by the cyclic freeze-thaw method. The fluidity of the two dressings in test tube before and after the first freeze-thawing was generally observed, and the difference in appearance of the final state of two dressings in 12-well plates were compared. According to random number table (the same grouping method below), the cell strains of L929 and HaCaT were both divided into water-soluble chitosan hydrogel group and control hydrogel group, respectively. After adding corresponding dressings and culturing for 24 h, the cell proliferation activity was measured using cell counting kit 8. Rabbit blood erythrocyte suspensions were divided into normal saline group, polyethylene glycol octyl phenyl ether (Triton X-100) group, water-soluble chitosan hydrogel group, and control hydrogel group, which were treated accordingly and incubated for 1 hour, and then the hemolysis degree of erythrocyte was detected by a microplate reader. Twenty-four female db/db mice aged 11-14 weeks were selected, and full-thickness skin defect wounds on their backs were inflicted and inoculated with the methicillin-resistant Staphylococcus aureus (MRSA), 72 h later, the mice were divided into blank control group, sulfadiazine silver hydrogel group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. On post injury day (PID) 0 (immediately), 7, 14, and 21, the healing of the wound was observed. On PID 14 and 21, the wound healing rate was calculated. On PID 14, MRSA concentration in wounds was determined. On PID 21, the wounds were histologically analyzed by hematoxylin and eosin staining; the expression of CD31 in the wounds was detected by immunofluorescence method, and its positive percentage was calculated. Raw264.7 cells were taken and divided into interleukin-4 (IL-4) group, blank control group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. At 48 h of culture, the percentages of CD206 positive cells were detected by flow cytometry. The number of samples was all 3. Data were statistically analyzed with independent sample t test, one-way analysis of variance, analysis of variance for repeated measurement, least significant difference test, and Dunnett T3 test. Results: Two dressings in test tube had certain fluidity before freeze-thawing and formed semi-solid gels after freeze-thawing for once. The final forms of two dressings in 12-well plates were basically stable and translucent sheets, with little difference in transparency. At 24 h of culture, the cell proliferation activities of L929 and HaCaT in water-soluble chitosan hydrogel group were significantly higher than those in control hydrogel group (with t values of 6.37 and 7.50, respectively, P<0.01). At 1 h of incubation, the hemolysis degree of erythrocyte in water-soluble chitosan hydrogel group was significantly lower than that in Triton X-100 group (P<0.01), but similar to that in normal saline group and control hydrogel group (P>0.05). On PID 0, the traumatic conditions of mice in the 4 groups were similar. On PID 7, more yellowish exudates were observed inside the wound in blank control group and control hydrogel group, while a small amount of exudates were observed in the wound in sulfadiazine silver hydrogel group and water-soluble chitosan hydrogel group. On PID 14, the wounds in blank control group and control hydrogel group were dry and crusted without obvious epithelial coverage; in sulfadiazine silver hydrogel group, the scabs fell off and purulent exudate was visible on the wound; in water-soluble chitosan hydrogel group, the base of wound was light red and obvious epithelial coverage could be observed on the wound. On PID 14, the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 21, the wound in water-soluble chitosan hydrogel group was completely closed, while the wounds in the other 3 groups were not completely healed; the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 14, the concentration of MRSA in the wound in water-soluble chitosan hydrogel group was significantly lower than that in blank control group (P<0.01), but similar to that in control hydrogel group and sulfadiazine silver hydrogel group (P>0.05). On PID 21, the new epidermis was severely damaged in blank control group; the epidermis on the wound in control hydrogel group also had a large area of defect; complete new epidermis had not yet being formed on the wound in sulfadiazine silver hydrogel group; the wound in water-soluble chitosan hydrogel group was not only completely covered by the new epidermis, the basal cells of the new epidermis were also regularly aligned. On PID 21, the percentage of CD31 positivity in the wound in water-soluble chitosan hydrogel group was (2.19±0.35)%, which was significantly higher than (0.18±0.05)% in blank control group, (0.23±0.06)% in control hydrogel group, and (0.62±0.25)% in sulfadiazine silver hydrogel group, all P<0.01. At 48 h of culture, the percentage of CD206 positive Raw264.7 cells in water-soluble chitosan hydrogel group was lower than that in IL-4 group (P>0.01) but significantly higher than that in blank control group and control hydrogel group (P<0.05 or P<0.01). Conclusions: The water-soluble chitosan hydrogel has good biosafety and can induce higher level of macrophage M2 polarization than control hydrogel without water-soluble chitosan, so it can enhance the repair effect of MRSA-infected full-thickness skin defect wounds in diabetic mice and promote rapid wound healing.
Mice ; Female ; Animals ; Rabbits ; Interleukin-4 ; Hydrogels/pharmacology* ; Wound Healing ; Chitosan/pharmacology* ; Diabetes Mellitus, Experimental ; Water ; Methicillin-Resistant Staphylococcus aureus ; Gelatin ; Polyvinyl Alcohol ; Hemolysis ; Saline Solution ; Eosine Yellowish-(YS) ; Hematoxylin ; Octoxynol ; Silver ; Phenyl Ethers ; Sulfadiazine

Connective tissue disease (CTD) are closely related to liver abnormality. CTD can affect the liver causing various degrees of liver injury, coexist with other liver diseases, especially autoimmune liver disease (ALD). Medications for CTD can also lead to liver injury or reactivate the hepatitis B virus. CTD patients can also be positive for ALD-related autoantibodies without corresponding manifestation; and vis versa. The diagnosis and differential diagnosis should be made on integrating clinical presentation, laboratory, imaging, and histological studies, not solely relying on autoantibody positivity.
Autoantibodies ; Autoimmune Diseases/diagnosis* ; Connective Tissue Diseases/diagnosis* ; Diagnosis, Differential ; Humans ; Liver