Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.
Humans ; Osteoclasts ; Alveolar Bone Loss/therapy* ; Cell Differentiation ; MicroRNAs ; Periodontitis/therapy* ; Extracellular Vesicles ; Apoptosis ; Mesenchymal Stem Cells

Objective:To evaluate the effects of exogenous biliverdin (BV) on the expression of Litaf in PC12 cells subjected to oxygen-glucose deprivation and restoration (OGD/R).Methods:PC12 cells were seeded in a 96-well cell culture plate at a density of 1×10 4 cells/well for 3 days and were divided into 3 groups ( n=18 each) by a random number table method: control group (group C), OGD/R group, and biliverdin group (BV group). Group C was incubated in a 37 ℃ incubator (95% air+ 5%CO 2) for 6 h. To establish the OGD/R model, cells were incubated with sugar-free medium in a 37 ℃ incubator (95% air+ 5%CO 2) for 2 h, and the medium was then replaced with normal medium and cells were continuously incubated in a 37 ℃ incubator (95% N 2+ 5% CO 2). In BV group, 2 μg/ml biliverdin was added immediately after oxygen-glucose restoration.Cells in 6 wells in each group were selected at 6 h of restoration for determination of the expression of Litaf protein and mRNA (by real-time polymerase chain reaction) and tumor necrosis factor-alpha (TNF-α) concentration (by enzyme-linked immunosorbent assay). Results:Compared with group C, the expression of Litaf protein and mRNA was significantly up-regulated, and TNF-α concentration in supernatant was increased in group OGD/R ( P<0.05). Compared with group OGD/R, the expression of Litaf protein and mRNA was significantly down-regulated, and TNF-α concentration in supernatant was decreased in group BV ( P<0.05). Conclusion:The mechanism by which exogenous biliverdin reduces OGD/R damage to PC12 cells is related to inhibiting up-regulated expression of Litaf and alleviating the inflammatory responses.

Objective:To evaluate the effect of propofol anesthesia on autophagy in hippocampal neurons of newborn rats.Methods:Thirty-nine healthy Sprague-Dawley rats, aged 7 days, weighing 10-12 g, were divided into 3 groups ( n=13 each) using a random number table method: control group (group C), fat emulsion group (group F) and propofol group (group P). Normal saline 8 ml/kg was intraperitoneally injected for 5 consecutive days in group C. Medium-/long-chain fatty emulsion injection 8 ml/kg was intraperitoneally injected for 5 consecutive days in group F. Medium-/long-chain propofol injection 80 mg/kg was intraperitoneally injected for 5 consecutive days in group P. Five rats were sacrificed on 1st day after the end of propofol anesthesia, and hippocampal tissues were taken for determination of the expression of microtubule-associated protein 1 light chain 3B (LC3B) and Beclin-1 (by Western blot). The remaining rats in each group underwent the Morris water maze test on 19th day after the end of propofol anesthesia (30 days after birth), and the escape latency, percentage of time of staying at the target quadrant and the number of crossing the original platform were recorded. Results:Compared with group C, no significant change was found in the expression of hippocampal LC3B and Beclin-1, escape latency, percentage of time of staying at the target quadrant, and the number of crossing the original platform in group F ( P>0.05), and the expression of hippocampal LC3B and Beclin-1 was significantly up-regulated, the escape latency was prolonged, percentage of time of staying at the target quadrant was decreased, and the number of crossing the original platform was decreased in group P ( P<0.05 or 0.01). Conclusion:The mechanism by which propofol anesthesia causes long-term cognitive dysfunction may be related to promoting autophagy in hippocampal neurons of newborn rats.

Objective To evaluate the present development and status of quality control for intensive care unit (ICU) in Sichuan Provincial traditional Chinese medicine (TCM) hospitals including integrated traditional Chinese and western medicine hospitals and ethnic hospitals, and to provide practical references for improving the service quality of ICU. Methods Supervisory Group of Sichuan Provincial Critical Care Medicine Quality Control Center of TCM was established in September 2018. From September 8th to 17th, 2018, according to the Scoring Criteria of Quality Control and Supervision Project of TCM for Critical Care Medicine, a 10-day quality control professional guidance was hand out to TCM hospitals with independent ICU in Sichuan Province. The service level of different aspects of hospital quality control was evaluated and ranked from equipment and resource support, medical team, service capacity and level, ward quality, completion of critical care core indicators, completion of quality control of TCM, development of new technologies, diagnosis and treatment schemes for dominant diseases. Results There were 52 TCM hospitals across the province that had an ICU. Thirty-three hospitals were third-class (63.5%), while the rest 19 hospitals were second-class (36.5%). Province-level, city-level and county-level hospitals were accounted for 9.6% (5/52), 38.5% (20/52), and 51.9% (27/52), respectively. Average bed ratio of ICU was 1.8%. Doctor-bed and guard-bed ratios were 0.71∶1 and 2.0∶1, respectively. The average annual admission rate of patients and the average daily admission rate of beds were higher, which were basically 1%. Ward quality was high; the incidence of nosocomial infection was controlled below 10%. Compliance rate of septic shock bundle treatment was high. The incidences of ventilator-associated pneumonia (VAP), catheter-related bloodstream infection (CRBSI) and catheter-associated urinary tract infection (CAUTI) were 0.45%, 0.22%, and 0.30%, respectively. Participation rate of TCM was about 83.4%. Average number of new technologies was about 4.4. Average number of disease schemes was about 2.62. Conclusions ICU of Sichuan Provincial TCM hospitals reaches the standard level in service capacity and level, ward quality, critical medicine quality control, and participation rate of TCM treatment. Improvements are required for other prospects, including department scale, medical personnel allocation, new technical development, diagnosis and treatment schemes of dominant diseases.

Objective To identify the role of IL-17A during respiratory syncytial virus (RSV) in-fection in a mouse model. Methods Female wild-type C57BL/6 mice and IL-17A knockout ( IL-17A-/-) mice at the age of 6 to 8 weeks were both randomly divided into two groups:control and RSV groups. Mice in the control groups were given the supernatant of Hep-2 cell culture, while those in the RSV groups were treated with RSV A2 through intranasal administration. Leukocytes in bronchoalveolar lavage fluid ( BALF) samples were counted. Left lung tissues were stained with hematoxylin and eosin ( HE ) to evaluate his-topathological scores. Airway hyperresponsiveness ( AHR) was measured by whole-body plethysmography. The concentrations of IFN-γ were determined with ELISA. RSV titers were measured by plaque assay. To assess the effects of IL-17A on IFN-γproduction and its role in RSV infection, IL-17A-/- mice were treated with exogenous recombinant murine IFN-γ or IL-17A, while wild-type mice were given IFN-γ neutralizing antibody intervention. Results The counts of inflammatory cells and neutrophils in BALF, lung tissue his-topathological scores, AHR, IFN-γlevels and virus titers of the wild-type group were higher than those of the IL-17A-/-group after RSV infection. IFN-γlevels, inflammatory cell counts in BALF, AHR and lung tissue histopathological scores were significantly increased in RSV-infected IL-17A-/- mice after the intervention of recombinant murine IL-17A or IFN-γ. RSV titers were much higher in the recombinant murine IL-17A-trea-ted group, but not affected by the recombinant murine IFN-γ intervention. Inflammatory cell counts in BALF, AHR and lung tissue histopathological scores were significantly decreased in RSV-infected wild-type mice following IFN-γ neutralizing antibody treatment, but no significant changes were found in RSV titers. Conclusions IL-17A might be involved in the pathogenesis of pulmonary diseases during RSV infection through promoting IFN-γ production and inhibiting viral clearance in mice.

Objective: To identify the role of interferon (IFN)-γ during respiratory syncytial virus (RSV) re-infection in mice. Method: Female wild type C57BL/6 mice and IFN-γ knockout mice (IFN-γ^-/- mice) at the age of 6 to 8 weeks were randomly divided into two groups: control group and RSV group, according to random number table.Each group was further divided into primary infection group and re-infection group.There were 8 groups.Mice were sacrificed on days 5, 7, 14 to collect samples.There were 5-8 mice in each group at each time point.And experiment was repeated twice. Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, left lung tissues were stained with HE and histopathological scoring (HPS) was performed.The concentrations of IFN-γ, IL-5, IL-13 were determined with ELISA.T test or single factor analysis of variance was used to compare between groups. Result: (1) Mice infected or reinfected with RSV showed pale hair, weight loss, decreased activity and anorexia.(2) IFN-γ levels significantly increased on days 5 and 7 following RSV primary infection and reinfection as compared to control groups in wild type mice ((192±44) vs.(36±8) and (531±161) vs.(23±4) pg/ml on day 5, (100±23) vs.(36±8) and (862±186) vs.(23±4) pg/ml on day 7, t=2.654, 2.513, 2.654, 3.968, all P<0.05). (3) Compared to the RSV-reinfected IFN-γ^-/- mice, RSV-reinfected wild type mice had less body weight loss ((13.6±2.6)% vs.(22.7±2.9)% on day 5, (18.0±3.1)% vs.(26.5±1.8)% on day 7, t=2.314, 2.308, both P<0.05), lower lung tissue histopathological score ((1.50±0.09) vs.(2.07±0.11) on day 5, (1.53±0.11) vs.(2.08±0.09) on day 7, (1.10±0.06) vs.(1.59±0.08) on day 14, t=3.916, 3.890, 4.837, all P<0.01), less BALF inflammatory cells count ((11.6±2.0) vs.(44.2±10.6)×10⁵/ml on day 5, (18.2±3.9) vs.(38.3±2.2)×10⁵/ml on day 7, t=2.818, 4.786, both P<0.05), and lower levels of IL-5 and IL-13 ((24±3) vs.(148±23), (23±4) vs.(169±26) pg/ml on day 5, (30±8) vs.(233±44), (20±5) vs.(182±19) pg/ml on day 7, (91±6) vs.(129±19), (62±8) vs.(132±5) pg/ml on day 14, t=5.252, 5.445, 4.517, 7.326, 3.816, 7.577, all P<0.01). Conclusion IFN-γ can alleviate airway inflammation following RSV reinfection in mice.

Objective To assess the efficacy and safety of peginterferon ( PegIFN) α-2b in treatment of HBeAg-positive chronic hepatitis B ( CHB).Methods Thirty two patients with HBeAg-positive CHB admitted in Peking University Shenzhen Hospital during November 2013 and January 2014 were recruited in the study.Patients were center randomly assigned into two groups : 22 patients in test group were treated with 180 μg PegIFN α-2b, 1 /w for 48 wk; 10 patients in control group were treated with 180 μg PegIFN α-2a (Pegasys), 1 /w for 48wk.All patients were followed up for 24wk after treatment.Virology markers, HBV DNA levels and liver functions were monitored regularly , and adverse events were observed . Fisher’s exact test was used to compare the efficacy and safety between two groups .Results There were no statistically significant differences between the control group and test group in ALT normalization rates , HBV DNA negative rates and HBeAg serological conversion rates both at the end of treatment and at the end of 24-wk follow-up (all P >0.05).Both groups had similar adverse effect incidence rates (P >0.05), but retina disease occurred in 7 cases of test group, which was not observed in control group .Conclusion Compared with PegIFN α-2a, PegIFN α-2b has similar efficacy and safety for patients with HBeAg -positive CHB.

Objective To explore the changes in serum and urine electrolytes of children with neurally media-ted syncope (NMS)after oral rehydration salts (ORS)[Ⅰ]treatment.Methods The study group included 135 patients [60 male and 75 female,aged 4 -16 years,average of (10.20 ±2.68)years old]with unexplained syncope and prodro-mal symptoms of syncope in our hospital between May 2014 and April 2015.The patients underwent head -up tilt test (HUTT),and completed serum electrolytes and 24 -hour urine electrolytes,and the serum electrolytes and 24 -hour u-rine electrolytes in different hemodynamic type of HUTT were compared.Positive HUTT patients were treated with health education and ORS[Ⅰ],while negative HUTT patients were received health education.Then 21 -154(42.63 ±27.71) days later,the patients returned to hospital,for the inquiry of symptom improvement,and review of HUTT,24 -hour urine and serum electrolytes.Results (1)The total effective rate of ORS[Ⅰ]treatment was 62.96% (17 /27 cases),while negative conversion rate of HUTT was 48.15% (13 /27 cases).(2)There was no significant difference in serum electro-lytes,24 -hour urine electrolytes or 24 -hour urine volume between HUTT positive group and negative group during the first visit (all P >0.05).(3)In return visit,serum calcium [(2.30 ±0.10)mmol/L vs (2.20 ±0.09)mmol/L,t =2.72,P <0.05]and serum phosphorus [(1.73 ±0.22)mmol/L vs (1.51 ±0.23)mmol/L,t =2.671,P <0.05]in HUTT positive group were significantly higher than those in negative group.The serum sodium,potassium,chloride,mag-nesium and 24 -hour urine electrolytes,24 -hour urine volume had no statistical difference(all P >0.05).(4)24 -hour urine sodium [(159.06 ±72.76)mmol/24 h vs (118.97 ±52.75)mmol/24 h,t =2.712,P <0.05],24 -hour urine chloride [(139.08 ±66.53)mmol/24 h vs (111.34 ±47.33)mmol/24 h,t =2.116,P <0.05]and 24 -hour urine volume [(1 564.21 ±829.39)mL vs (1 058.95 ±509.92)mL,t =3.371,P <0.01]after ORS[Ⅰ]treatment were sig-nificantly higher than those before ORS[Ⅰ]treatment.The serum electrolytes and 24 -hour urine potassium,calcium, phosphorus,magnesium had no statistical difference (all P >0.05).(5)There was no significant difference in serum elec-trolytes,24 -hour urine electrolytes or 24 -hour urine volume between vasovagal syncope group and postural orthostatic tachycardia syndrome group during the first visit(all P >0.05).Conclusions ORS[Ⅰ]treatment can obviously increase the 24 -hour urine sodium,24 -hour urine chloride in children with NMS.ORS[Ⅰ]is an effective therapy for NMS.

Objective To explore the circadian rhythm of neurally mediated syncope (NMS)in children. Methods There were 21 6 children with NMS included in the study,including 91 male and 1 25 female,aged from 4 to 1 7 years old with a mean age of (1 1 .34 ±2.65)years,who came from the Specialist Syncope Outpatient Department or Inpatient Department of the Second Xiangya Hospital of Central South University from December 201 3 to October 201 5. The patients were divided into vasovagal syncope (VVS)group and postural tachycardia syndrome (POTS)group ac-cording to head -up tilt test (HUTT)results,including 1 78 VVS patients and 38 POTS patients.Ninety -four patients with NMS were in the <1 2 years old group[(8.88 ±1 .88)years old]and 1 22 subjects with NMS were in the ≥1 2 years old group[(1 3.24 ±1 .1 8)years old].All patients or guardians were carefully asked about the number of synco-pal attacks and the periods in which episodes occurred in before HUTT [24 hours of a day were divided into 4 periods:morning (0600 AM-1 200 AM),afternoon (1 200 AM-1 800 PM),evening (1 800 PM-2400 PM), night (0000 AM-0600 AM)].Results (1 )General data:the total syncopal episodes of 21 6 children with NMS were 61 4 episodes,including 1 78 VVS patients with 471 syncopal episodes in total and 1 43 attacks of 38 children with POTS.There were 273 episodes of 94 patients in the <1 2 years old group and 341 episodes of 1 22 subjects in the ≥1 2 years old group.There were no significant differences in the diurnal variation of syncopal episodes between the VVS group and POTS group regarding age and gender (P >0.05).(2)The number of syncopal episodes in patients with VVS which occurred in the morning hours was strikingly higher than that of afternoon,evening or nighttime (P <0.05).But there was no significant difference in the frequency of episodes in different periods through the day in the POTS group (P >0.05).Patients with VVS had a higher proportion of episodes in the morning but a lower proportion in the evening when compared with the POTS group (P <0.05).(3)The male children with NMS tended to have a higher proportion of episodes in the morning than the female patients(χ2 =1 1 .001 ,P =0.01 2).(4)There seemed to be no difference in the frequency of syncopal episodes through the day between the <1 2 years old group and the ≥1 2 years old group(χ2 =1 .995,P =0.573).Conclusions The frequency of syncopal episodes in children with VVS displayed a clear circadian rhythm,with a peak in the morning,but the POTS patients did not show a circadian variation.The male children with NMS tended to have a higher proportion of episodes in the morning than the female patients.

BACKGROUND:A variety of cel growth factors are involved in skeletal muscle regeneration; moreover, these factors cooperate with each other to promote muscle repair and regeneration. OBJECTIVE:To explore the synergy mechanism of a variety of cel growth factors in promoting damage repair. METHODS:By using literature survey, Wanfang, CNKI and PubMed databases were searched for articles related to exercise-induced muscle damage and repair using the keywords of “cel growth factor; skeletal muscle damage;repair; fibroblast growth factor” in Chinese and English, respectively. Research achievements related to exercise-induced muscle damage, molecular biological characteristics of cel growth factors and skeletal muscle injury repair are discussed. RESULTS AND CONCLUSION: Basic fibroblast growth factor plays a basic biological role to promote cel proliferation and angiogenesis, which is the strongest cytokine known to promote cel growth and reflects a very important role in skeletal muscle repair. Epidermal growth factor is synthesized by monocytes and ectodermal cels, which is prominent to stimulate the division and proliferation of a variety of tissues and cels, enhance cel movement, division and synthesis of interstitial protein. Insulin-like growth factors are a family of insulin-like growth factor 1-related and insulin-like growth factor 2-related peptides, which can promote muscle protein synthesis, promote muscle cel proliferation and differentiation, and participate in skeletal muscle regeneration and repair, thereby accelerating wound healing of the muscles. Neurotrophic factor is a kind of trace soluble substances around sensory neurons and produced by neuron-targeted cels, which can specificaly promote neuronal growth and maintenance, and promote skeletal muscle repair. But studies on the synergy mechanism of a variety of cel growth factors in the repair of exercise-induced muscle damage are just at the initial stage, and further research is necessary.