OBJECTIVETo explore the clinical effects of lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine ( Fuchunsan ) on the treatment of postburn hyperplastic scar.

METHODSSixty-three patients with hyperplastic scar after burn injury hospitalized from February 2012 to June 2014 in our department were treated with lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine (Fuchunsan). Patients were divided into early stage group (E, n = 35), middle stage group (M, n = 25), and late stage group ( L, n = 3) according to the formation time of scar, which was respectively 3 weeks to 3 months, longer than 3 months and less than or equal to 6 months, and 3 to 15 years in groups E, M, and L. The number of times of laser treatment of patients in each group was recorded. The degree of scar pain in patients of the three groups was assessed by the Numerical Rating Scale (NRS) before treatment and after treatment for 1, 2, and 3 times. The scar condition of patients in groups E and M was assessed by the Vancouver Scar Scale (VSS) before treatment and after treatment for 1, 3, and 5 times. Patients in group L did not receive VSS assessment but were evaluated by clinical observation only. Photos of scar in treating area were taken before treatment and after treatment for 3 and 5 times to evaluate the clinical effect. Data were processed with t test.

RESULTSPatients in groups E and M were treated with laser for (4.8 ± 1.1) and (7.7 ± 2.1) times respectively. In group L, the treatment was stopped in 2 patients after laser treatment for 5 times, and 1 patient received laser treatment for 12 times. The degree of pain in patients of groups E and M was alleviated significantly after treatment for one time, and the number of patients scoring 1-4 point(s) in NRS increased from 5 cases to 38 cases. After treatment for 2 and 3 times, the increase in the number of patients scoring 1-4 point (s) in NRS was on a small scale. Before treatment and after treatment for 1 time, VSS scores of patients in groups E and M were similar (with values respectively 0.641 and 0. 082, P values above 0. 05). After treatment for 3 and 5 times, VSS scores of patients in group E were respectively (9.2 ± 0.8) and (7.0 ± 1.1) points, which were significantly lower than those in group M [ (9.7 ± 1.0) and (8.2 ± 1.0) points, with values respectively -1.993 and -4.433 , P < 0.05 or P < 0.01]. After treatment for 3 times, the rate of improvement in appearance was respectively 88.6% (31/35) and 72.0% (18/25) in groups E and M, and it was respectively 100.0% (35/35) and 96.0% (24/25) after treatment for 5 times. No significant effect in appearance was found in the 3 patients in group L.

CONCLUSIONSEarly application of lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine (Fuchunsan) for the treatment of postburn hyperplastic scar is effective.

Burns ; Cicatrix ; etiology ; prevention & control ; Humans ; Lasers, Gas ; therapeutic use ; Medicine, Chinese Traditional ; Postoperative Care ; methods ; Postoperative Complications ; prevention & control ; Treatment Outcome

Objective To investigate the effect of sevoflurane postconditioning on the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase during myocardial ischemia-reperfusion (I/R) in rats and the possible mechanism. Methods Forty-five healthy male Wistar rats weighing 250-280 g were randomly divided into 3 groups ( n = 15 each): sham operation group (group S), I/R group and sevoflurane postconditioning group (group Spo). Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion. In group S the anterior descending branch was only exposed but not ligated. Group Spo received 5 min inhlation of 2.5% sevoflurane 1 min before reperfusion. The myocardial tissues were taken at 2 h of reperfusion for determination of infarct size and activities of Na+ -K+ -ATPase and Ca2 * -Mg2 * -ATPase. Results The infarct size was significantly larger and the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase were signifi cantly lower in group I/R than in group S ( P ＜ 0.05). The infarct size was significantly smaller and the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase were significantly higher in group Spo than in group I/R (P ＜ 0.05 ). Conclusion Sevoflurane postconditioning can reduce myocardial I/R injury through increasing the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase.

Objective To evaluate the cost-utility of different hepatitis E vaccination strategies in women aged 15 to 49.Methods The Markov-decision tree model was constructed to evaluate the cost-utility of three hepatitis E virus vaccination strategies.Parameters of the models were estimated on the basis of published studies and experience of experts.Both methods on sensitivity and threshold analysis were used to evaluate the uncertainties of the model.Results Compared with non-vaccination group,strategy on post-screening vaccination with rate as 100％,could save 0.10 quality-adjusted life years per capital in the women from the societal perspectives.After implementation of screening program and with the vaccination rate reaching 100％,the incremental cost utility ratio (ICUR) of vaccination appeared as 5 651.89 and 6 385.33 YuaWQALY,respectively.Vaccination post to the implementation of a screening program,the result showed better benefit than the vaccination rate of 100％.Results from the sensitivity analysis showed that both the cost of hepatitis E vaccine and the inoculation compliance rate presented significant effects.If the cost were lower than 191.56 Yuan (RMB) or the inoculation compliance rate lower than 0.23,the vaccination rate of 100％ strategy was better than the post-screening vaccination strategy,otherwise the post-screening vaccination strategy appeared the optimal strategy.Conclusion Post-screening vaccination for women aged 15 to 49 from social perspectives seemed the optimal one but it had to depend on the change of vaccine cost and the rate of inoculation compliance.

Objective: To investigate the interventional effects of BAY11-7082 on lung inflammatory response at the early stage and acute lung injury of rats with severe burns. Methods: (1) Experiment 1. Twelve Sprague-Dawley (SD) rats were divided into control (C) group and burn (B) group according to the random number table, with 3 rats in group C and 9 rats in group B. Rats in group C did not receive any special treatment. Rats in group B were inflicted with 30% total body surface area full-thickness burn on the back. Immediately after injury, rats in group B were intraperitoneally injected with normal saline in the dosage of 50 mL/kg. Abdominal aorta blood and lung tissue samples were collected from three rats in group B at post injury hour (PIH) 12, 24, and 48, respectively. The interleukin-1β (IL-1β) and the IL-18 content of serum were determined with enzyme-linked immunosorbent assay. The mRNA expressions of IL-1β and IL-18 in lung tissue were determined with real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR). Sample collection and determination in rats of group C were performed as above. (2) Experiment 2. Eighteen SD rats were divided into control (C) group, simple burn (SB) group, and BAY11-7082 intervention (BI) group according to the random number table, with 6 rats in each group. Rats in group C did not receive any special treatment. Rats in groups SB and BI were inflicted with injury as in experiment 1. Immediately after injury, rats in group SB were intraperitoneally injected with normal saline in the dosage of 50 mL/kg, and those in group BI with 8 mg/mL (final mass concentration) BAY11-7082 solution in the dosage of 50 mL/kg. Lung tissue and bronchoalveolar lavage fluid (BALF) of rats with burns were collected at the optimal observation time point concluded from experiment 1. The morphology of lung tissue was observed with hematoxylin-eosin staining, and the pathological damage of lung tissue was graded. The myeloperoxidase (MPO) content of lung tissue and the total protein content of BALF were detected by microplate reader. The protein expressions of nucleotide-binding oligomerization domain-like receptor-3 (NLRP3) and cysteine-aspartic proteases 1 (caspase-1) in lung tissue were determined with Western-blotting. The mRNA expressions of IL-1β, IL-18, NLRP3, and caspase-1 in lung tissue were determined with real-time fluorescence quantitative RT-PCR. Sample collection and determination in rats of group C were performed as above. Data were processed with one-way analysis of variance and LSD-t test. Results: (1) The IL-1β and IL-18 content of serum in rats of group B at PIH 12, 24, and 48 were significantly higher than those of group C (t=10.55, 22.05, 12.47, 10.60, 15.22, 11.94, P<0.01). The mRNA expressions of IL-1β and IL-18 in rats of group B at PIH 12, 24, and 48 were significantly higher than those of group C (t=3.62, 7.19, 5.28, 3.20, 12.62, 7.31, P<0.05 or P<0.01). PIH 24 was the optimal observation time point for the following experiment. (2) At PIH 24, compared with those in group SB, the inflammatory cell infiltration and erythrocyte exudates of alveolar in group BI were obviously reduced, and the pulmonary interstitial edema obviously subsided. The pathological damage score of lung tissue in rats of group SB was (9.00±1.00) points, significantly higher than (1.10±0.26) points of group C (t=13.23, P<0.01). The pathological damage score of lung tissue in rats of group BI was (4.93±0.70) points, which was significantly lower than that of group SB (t=5.76, P<0.01) but still significantly higher than that of group C (t=8.84, P<0.01). At PIH 24, the MPO content of lung tissue and the total protein content of BALF in rats of group SB were (1.83±0.15) U/mg and (1.39±0.20) mg/mL, respectively, significantly higher than (0.51±0.10) U/mg and (0.44±0.05) mg/mL of group C (t=12.50, 7.86, P<0.01). The MPO content of lung tissue and the total protein content of BALF in rats of group BI were (0.91±0.12) U/mg and (0.60±0.10) mg/mL, respectively, significantly lower than those of group SB (t=8.36, 6.06, P<0.01). At PIH 24, the protein expressions of NLRP3 and caspase-1 in lung tissue of rats of group SB were 3.10±0.09 and 2.99±0.30, respectively, significantly higher than 1.00 and 1.00 of group C (t=9.06, 11.28, P<0.01). The protein expressions of NLRP3 and caspase-1 in lung tissue of rats of group BI were 1.13±0.08 and 1.81±0.11, respectively, significantly lower than those of group SB (t=7.24, 3.91, P<0.05 or P<0.01). At PIH 24, the mRNA expressions of IL-1β, IL-18, NLRP3, and caspase-1 in lung tissue of rats in group SB were 5.0±0.4, 3.32±0.21, 3.54±0.42, and 6.3±1.0, respectively, significantly higher than 1.0, 1.00, 1.00, and 1.0 of group C (t=13.97, 14.14, 11.78, 7.13, P<0.01). The mRNA expressions of IL-1β, IL-18, NLRP3, and caspase-1 in lung tissue of rats in group BI were 2.6±0.5, 2.00±0.28, 1.39±0.21, and 2.5±0.5, respectively, significantly lower than those of group SB (t=7.11, 5.80, 9.99, 4.65, P<0.05 or P<0.01). Conclusions Applying BAY11-7082 at the early stage of acute lung injury of rats with severe burn can reduce the expression of caspase-1, decrease the levels of IL-1β and IL-18, and decrease the MPO content of lung tissue and the total protein content of BALF through inhibiting NLRP3, thus alleviating the lung inflammatory response and lung injury.

Objective To investigate the efficacy and safety of regional citrate anticoagulation (RCA) for continuous veno-venous hemofiltration (CVVH) in patients with severe trauma.Methods Sixty-four patients with severe trauma who needed to apply continuous renal replacement therapy (CRRT) and were admitted into the department of critical care medicine in Tianjin Hospital from June 2013 to August 2015 were enrolled in the study.According to the patient's actual condition,they were divided into two groups:no anticoagulant group (29 cases) and RCA group (35 cases).The filter lifetime,after treatment the activated partial thromboplastin time (APTT),acid-base balance,free calcium ([Ca2+]i) and serum sodium (Na+) concentrations,bleeding episodes were compared between the two groups.Results The average filter lifetime in RCA group was longer than that in no anticoagulant group (hours:50.7 ± 11.3 vs.4.9 ± 1.2,P ＜ 0.01).After the end of treatment,the levels of APTT (s:30.7 ± 8.8 vs.32.1 ± 7.3),pH value (7.41 ± 0.09 vs.7.40 ± 0.07),[Ca2+]i (mmol/L:2.13 ± 0.20 vs.2.21 ± 0.17),and Na+ (mmol/L:139 ± 8 vs.141 ± 6) were ofno significant differences between the RCA group and the no anticoagulant group (all P ＞ 0.05).The incidence of clinicalbleeding in RCA group was lower than that in no anticoagulant group [2.9％ (1/35) vs.13.8％ (4/29)],but the differencewas not statistically significant (P ＞ 0.05).Conclusions RCA-CVVH is a safe and effective therapeutic method inpatients with severe trauma who need for CRRT,the stability of internal environment is not affected and no incidence ofclinical bleeding event is increased.

Dopamine D₃ receptor (D₃R) is implicated in multiple psychotic symptoms. Increasing the D₃R selectivity over dopamine D₂ receptor (D₂R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D₃R selective ligands. Through a structure-based virtual screen, ZLG-25 (D₃R K_i = 685 nmol/L; D₂R K_i > 10,000 nmol/L) was identified as a novel D₃R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D₃R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD₃R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins