The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

ObjectiveTo explore the effect of flipped classroom mode in the clinical probation teaching for undergraduate mental health students， so as to expand the new mode of clinical teaching in psychiatry department. MethodsA total of 85 undergraduate psychiatric students from Xinxiang Medical University in 2016 were selected. All participants were divided into experimental group （n=43） and control group （n=42） according to the random number table method. The flipped classroom clinical teaching mode was adopted to experimental group， and the traditional practice mode for control group. The probation lasted for 12 weeks. Theoretical knowledge of symptomology， psychiatric clinical skills （OSCE）， doctor-patient communication ability（SEGUE） and clinical thinking ability were assessed at the end of probation. ResultsAfter the probation， students in experimental group obtained higher scores in theoretical knowledge， clinical skills， doctor-patient communication ability and clinical thinking ability compared with control group. The differences were statistically significant ［（33.08±1.72） vs. （32.06±2.33）， （51.61±2.12） vs. （48.32±2.86）， （18.14±1.98） vs. （14.62±2.15）， （91.26±14.13） vs. （82.40±10.89）， t=2.307， 6.034， 3.230， 7.846， P<0.05 or 0.01］. ConclusionApplying the flipped classroom mode into the clinical probation teaching for mental health undergraduate students may help to improve students' theoretical knowledge level and clinical operation ability， faciliate doctor-patient communication， and have a positive impact on their clinical thinking ability.

Purpose: Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. This study reported the first real-world data of pyrotinib-based therapy in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on efficacy in lapatinib-treated patients and in brain metastasis. Materials and Methods: One hundred thirteen patients with metastatic HER2-positive BC treated with pyrotinib-based therapy in Fudan University Shanghai Cancer Center under non-clinical trial settings from September 1, 2018 to March 1, 2019 were included. Results: Over half patients have received more than two lines of systematic therapy and exposed to two or more kinds of anti-HER2 agents. Most patients received a combined therapy, commonly of pyrotinib plus capecitabine, or vinorelbine or trastuzumab. Median progression-free survival (PFS) was 6.3 months (range, 5.54 to 7.06 months) and objective response rate (ORR) was 29.5%, with two patients (1.9%) achieving complete response. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (9.0 months vs. 5.4 months, p=0.001). ORR for lapatinib-treated patients was 23.2%. Thirty-one of 113 patients have brain metastasis. Median PFS was 6.7 months and intracranial ORR was 28%. For patients without concurrent radiotherapy and/or brain surgery, the ORR was very low (6.3%). But for patients receiving concurrent radiotherapy and/or brain surgery, the ORR was 66.7%, and three patients achieved complete response. Most common adverse event was diarrhea. Conclusion Pyrotinib-based therapy demonstrated promising effects in metastatic HER2-positive BC and showed activity in lapatinib-treated patients. For patients with brain metastasis, pyrotinib-based regimen without radiotherapy showed limited efficacy, but when combined with radiotherapy it showed promising intracranial control.

Objective To explore the rapid eye movement (REM) sleep characteristics of different episode types of depression and post-stroke depression (PSD) patients and provide support for clinical diagnosis,treatment and prognosis.Methods Patients with single-episode depression (group A,n =22),patients with recurrent depression (≥ 2 episodes,group B,n=26) and patients with PSD (group C,n=19)were included from Henan Provincial Mental Hospital.20 healthy volunteers were assigned to control group.Participants in the 4 groups were performed polysomnographic recordings (PSG) from 9 PM to 6 AM before treatment.The 3 patients groups were performed the second PSG recordings and HAMD score at the end of 6 week SSRIs treatment.The REM indexes of 4 groups were compared and analyzed.Results First PSG detection showed that REM sleep latencies (RL) were shorter in group A and B (A:(65.57±18.29) min,B:(66.32±15.46) min) than that in group C ((79.17±20.18) min) and control group((87.24±16.55)min);REM activity (RA) (A:(99.82±25.71) u,B:(104.70±28.23) u)and REM density (RD) (A:(81.06± 19.35)％,B:(86.61±23.83) ％) were increased more significantly in group A and B than those in control group ((79.61 ± 18.40) u;(68.11 ± 17.54) ％);REM sleep time (RT) were decreased more signifi-cantly in group C ((51.66±22.26) min) than that in group A((71.43±20.70) min),group B((74.81±17.52) min) and control group ((70.46±16.35) min)(P＜0.05).After treatment,REM sleep latency was prolonged in group A ((65.57±18.29) min vs (81.71±21.62) min),and REM activity was decreased in group A((99.82±25.71) u vs (83.58±27.19) u),the difference was statistically significant (P＜0.05).REMdensity was decreased,but the difference was not statistically significant (P＞0.05).There was no significant difference in the indexes of REM in group C;RT was prolonged ((51.66± 22.26) min vs (68.37 ± 20.16)min) in group C,the difference was statistically significant (P＜0.05).Conclusion Most of depression patients with different episode types have REM disinhibition phenomenon.RD increase may be REM characteristic type of depression patient.Sleep disorders of PSD patients are mainly poor sleep process and sleep continuity and have no characteristics of REM sleep disorder of depression ones.

-β2 was positively correlated with OPG (r=0. 432,P<0. 01). Conclusions The reference ranges of serum TGF-β1 and TGF-β2 in healthy adult females are established. Both TGF-β1 and TGF-β2 of them are correlated with OPG and ieptin.