Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

OBJECTIVE To analyze the characteristics of levofloxacin-induced hypersensitivity reaction. METHODS Clinical pharmacists participated in the treatment for a case of levofloxacin-induced hypersensitivity reaction， and adjudged the relationship of levofloxacin with hypersensitivity reaction according to relative standards. Retrieved from CNKI， VIP， Wanfang database， PubMed and Embase， relevant literature about levofloxacin-induced hypersensitivity reaction was collected and analyzed. RESULTS Clinical pharmacists suggested checking the patient’s previous medication and allergy history based on symptoms such as fever and systemic rash， and determined that the drug hypersensitivity was “likely” or “highly likely” to be associated with levofloxacin. Clinicians provided symptomatic treatment to the patient based on the judgment of clinical pharmacists， and the patient improved after treatment. Results of the literature analysis showed that among 31 involved patients， there were 23 males and 8 females； 18 patients aged 50 and above； the incubation period of 24 patients was within 4 days after medication. The main adverse drug reactions were drug hypersensitivity syndrome， fixed drug eruption， erythema multiforme， etc. Most patients were improved after withdrawal and symptomatic treatment. CONCLUSIONS Hypersensitivity reaction is the rare adverse drug reaction of levofloxacin， mostly occurring within 2.5 h to 4 days after administration， and it is more likely to occur in middle-aged and elderly patients. Before clinical use， patients should be asked about their drug allergy history in detail； when patients experience fever or rash without obvious causes， medication should be stopped promptly and symptomatic treatment should be taken to ensure the safety and effectiveness of the patients’ medication.

Objective To investigate the anti-inflammatory effect and mechanism of sappanone A(SA)on lipopolysaccharide(LPS)-induced RAW264.7 cell model based on JAK2-STAT3 signaling pathway.Methods MTT assay was used to detect the effects of sappanone A,LPS and AG490 on RAW264.7 cell viability.The LPS-induced inflammatory model in RAW264.7 cells was established,and the secretion level of interleukin-6(IL-6)in the supernatant was detected by ELISA.mRNA expressions of IL-6,Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)were tested by RT-PCR.The protein expressions of JAK2,phosphorylated JAK2(p-JAK2),STAT3 and phosphorylated STAT3(p-STAT3)were determined by Western Blot.Results Compared with control group,IL-6 secretion level was significantly increased,mRNA expressions of IL-6,JAK2 and STAT3 were up-regulated,and protein expressions of p-JAK2 and p-STAT3 were increased(all P＜0.01)in model group.Compared with model group,high-dosed sappanone A(5 μg·mL-1)was significantly decreased the secretion of IL-6,down-regulated the mRNA expressions of IL-6,JAK2 and STAT3,and inhibited the protein expressions of p-JAK2 and p-STAT3(all P＜0.01).Conclusion Sappanone A may play an anti-inflammatory role by inhibiting the JAK2-STAT3 signaling pathway and hence inhibiting the secretion of IL-6.

As a novel technology, wearable physiological parameter monitoring technology represents the future of monitoring technology. However, there are still many problems in the application of this kind of technology. In this paper, a pilot study was conducted to evaluate the quality of electrocardiogram (ECG) signals of the wearable physiological monitoring system (SensEcho-5B). Firstly, an evaluation algorithm of ECG signal quality was developed based on template matching method, which was used for automatic and quantitative evaluation of ECG signals. The algorithm performance was tested on a randomly selected 100 h dataset of ECG signals from 100 subjects (15 healthy subjects and 85 patients with cardiovascular diseases). On this basis, 24-hour ECG data of 30 subjects (7 healthy subjects and 23 patients with cardiovascular diseases) were collected synchronously by SensEcho-5B and ECG Holter. The evaluation algorithm was used to evaluate the quality of ECG signals recorded synchronously by the two systems. Algorithm validation results: sensitivity was 100%, specificity was 99.51%, and accuracy was 99.99%. Results of controlled test of 30 subjects: the median (Q1, Q3) of ECG signal detected by SensEcho-5B with poor signal quality time was 8.93 (0.84, 32.53) minutes, and the median (Q1, Q3) of ECG signal detected by Holter with poor signal quality time was 14.75 (4.39, 35.98) minutes (Rank sum test,
Algorithms ; Electrocardiography ; Electrocardiography, Ambulatory ; Humans ; Pilot Projects ; Signal Processing, Computer-Assisted ; Wearable Electronic Devices

OBJECTIVE: To introduce the skills clinical pharmacists applied in guiding the use of insulin and its analogs in patients with type 2 diabetes mellitus.METHODS: The related knowledge needed to be mastered by clinical pharmacists were reviewed,and based on our clinical practice,the skills in offering guidance for the use of insulin and its analogs in patients with type 2 diabetes mellitus were proposed.RESULTS & CONCLUSION: Clinical pharmacists can take advantage of their expertise and skills accumulated in clinical practice to provide better pharmaceutical care for patients with type 2 diabetes mellitus.