This article reports a postcraniotomy patient with renal insufficiency and electrolyte imbalance who developed ventilator-associated pneumonia caused by extensively drug-resistant Klebsiella pneumoniae.According to the patient's pathophysiological characteristics,bacterial epidemiological characteristics,and bacterial culture results,combined with the latest guidelines and the pharmacokinetic/pharmacodynamic characteristics of antibiotics,a full-dose ceftazidime/avibactam regimen was initially suggested by the clinical pharmacist,and which was adopted by doctor.When the effect of ceftazidime/avibactam was poor and no guideline-recommended alternatives were available,the clinical pharmacist,in conjunction with clinical experience,proposed a combination therapy of colistin sulfate and tigecycline,with the implementation of adverse reaction monitoring and mucin sulfate blood concentration monitoring.Finally,the pneumonia was effectively controlled,the inflammatory indicators such as temperature and the white blood cell count returned to normal,no adverse drug reactions occurred,and the patient was successfully transferred to the rehabilitation institution.Clinical pharmacists stay updated on the latest medication knowledge both domestically and internationally,recommend advanced drug treatment protocols for clinical practice,assist in managing severe infections,and play an important role in the clinical team.

This article reports a postcraniotomy patient with renal insufficiency and electrolyte imbalance who developed ventilator-associated pneumonia caused by extensively drug-resistant Klebsiella pneumoniae.According to the patient's pathophysiological characteristics,bacterial epidemiological characteristics,and bacterial culture results,combined with the latest guidelines and the pharmacokinetic/pharmacodynamic characteristics of antibiotics,a full-dose ceftazidime/avibactam regimen was initially suggested by the clinical pharmacist,and which was adopted by doctor.When the effect of ceftazidime/avibactam was poor and no guideline-recommended alternatives were available,the clinical pharmacist,in conjunction with clinical experience,proposed a combination therapy of colistin sulfate and tigecycline,with the implementation of adverse reaction monitoring and mucin sulfate blood concentration monitoring.Finally,the pneumonia was effectively controlled,the inflammatory indicators such as temperature and the white blood cell count returned to normal,no adverse drug reactions occurred,and the patient was successfully transferred to the rehabilitation institution.Clinical pharmacists stay updated on the latest medication knowledge both domestically and internationally,recommend advanced drug treatment protocols for clinical practice,assist in managing severe infections,and play an important role in the clinical team.

Tumor recurrence and metastasis is the leading cause of mortality for postoperative breast cancer patients. However, chemotherapy intervention after surgery is often unsatisfactory, because residual microtumors are difficult to target and require frequent administration. Here, an all-in-one and once-for-all drug depot based on in situ-formed hydrogel was applied to fit the irregular surgical trauma, and enable direct contact with residual tumors and sustained drug release. Our immunological analysis after resection of orthotopic breast tumor revealed that postsurgical activation of CXCR4-CXCL12 signal exacerbated the immunosuppression and correlated with adaptive upregulation of PD-L1 in recurrent tumors. Thus, a multifunctional hydrogel toolkit was developed integrating strategies of CXCR4 inhibition, immunogenicity activation and PD-L1 blockade. Our results showed that the hydrogel toolkit not only exerted local effect on inhibiting residual tumor cell "seeds" but also resulted in abscopal effect on disturbing pre-metastatic "soil". Furthermore, vaccine-like effect and durable antitumor memory were generated, which resisted a secondary tumor rechallenge in 100% cured mice. Strikingly, one single dose of such modality was able to eradicate recurrent tumors, completely prevent pulmonary metastasis and minimize off-target toxicity, thus providing an effective option for postoperative intervention.

Multidrug resistance (MDR) has been considered as a huge challenge to the effective chemotherapy. Therefore, it is necessary to develop new strategies to effectively overcome MDR. Here, based on the previous research of -(2-hydroxypropyl)methacrylamide (HPMA) polymer-drug conjugates, we designed an effective system that combined drug-efflux circumvention and mitochondria targeting of anticancer drug doxorubicin (Dox). Briefly, Dox was modified with mitochondrial membrane penetrating peptide (MPP) and then attached to (HPMA) copolymers (P-M-Dox). Our study showed that macromolecular HPMA copolymers successfully bypassed drug efflux pumps and escorted Dox into resistant MCF-7/ADR cells endocytic pathway. Subsequently, the mitochondria accumulation of drugs was significantly enhanced with 11.6-fold increase by MPP modification. The excellent mitochondria targeting then resulted in significant enhancement of reactive oxygen species (ROS) as well as reduction of adenosine triphosphate (ATP) production, which could further inhibit drug efflux and resistant cancer cell growth. By reversing Dox resistance, P-M-Dox achieved much better suppression in the growth of 3D MCF-7/ADR tumor spheroids compared with free Dox. Hence, our study provides a promising approach to treat drug-resistant cancer through simultaneous drug efflux circumvention and direct mitochondria delivery.

OBJECTIVE:To provide reference for strengthening the safety of the combination use of CYP3A4 inhibitors with statins in clinical treatment. METHODS:30 cases per month(totally 300 cases)(the hospitalization time was more than 10 days) discharged from the cardiology department of a third-level class A hospital during Jan. to Oct. 2013 were selected randomly,and statistical analysis was made into general information of patients,whether to use statins and CYP3A4 inhibitor,and whether to monitor safety indicators of liver and kidney function and creatine kinase. RESULTS:Totally 291 patients were treated with statins with a total use rate of 97%,including 265 cases of atorvastatin and 11 cases of simvastatin. The CYP3A4 inhibitors were com-bined with amlodipine,diltiazem,verapammy,amiodarone,Ginkgo biloba leaf,fenofibrate and clarithromycin,etc.,and 162 (59%) patients were given the combination use of simvastatin or atorvastatin with CYP3A4 inhibitors. But the liver and kidney function,creatine kinase and other safety indicators were not monitored by laboratory examination during medication. CONCLU-SIONS:Atorvastatin and simvastatin are used commonly in patients with cardiovascular disease,and the combination use rate with CYP3A4 inhibitor is relatively higher and needs long-term medication,drug dosage should be limited according to the direction of instructions and the adverse reactions induced by drug interactions should be noticed to strengthen medication monitor and education for patients.