A rapid resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometric (RRLC-Q-TOF-MS) method was established and optimized for the analysis of pharmacokinetic behavior of ginsenoside Rb2 in rats by intravenous injection administration.The metabolism of ginsenosides Rb2 in vivo rat was also explored.In the experiment,Agilent SB C18 column was selected for the sample separation with 0.1％ aqueous formic acid solution as mobile phase (A) and acetonitrile as mobile phase (B) at a flow rate of 0.2 mL/min,and the injection volume was set to 5 μL.Q-TOF-MS was carried out in electron pray ionization (ESI) negative ion mode.The limit of quantification (LOQ,S/N =10) and limit of detection (LOD,S/N=3) were 0.10 and 0.08 μg/mL,respectively,and the linear range was 0.1-1.26 μg/mL.The experiment results showed that the concentration-time profile of ginsenoside Rb2 conformed to a two-compartment pharmacokinetic model after intravenous administration for rats.The mean plasma elimination half-lives were (23.58±1.10) min (t1/2α),(1306.55±147.23) min (t1/2β) for Rb2.By analyzing the urine of rats after intravenous administration and the fecal samples after oral administration of ginsenoside Rb2,it was found that the metabolites were M6,M2 (CY),F2,and C-K.

Objective:To investigate the number of necroptotic renal tubular epithelial cells in renal tissues of patients with chronic kidney disease (CKD) and the correlation with clinicopathologic parameters, and explore its role in the progression of the excessive loss of renal tubular cells and chronic kidney injury.Methods:Renal tissue samples from 60 patients (18-65 years old) with CKD proven by kidney biopsy in the First Affiliated Hospital of Hainan Medical University from June 2017 to June 2019 were collected. According to internationally accepted K/DOQI guidelines, the patients were divided into 1-4 stages of CKD, with 15 cases in each stage. The number of necroptotic renal tubular epithelial cells in patients with different stages of CKD was detected using receptor-interacting protein 3 (RIP3) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) fluorescent staining, and the expression of RIP3 and MLKL, marker protein of necroptosis, was detected by immunohistochemistry. Pearson correlation analysis was used to analyze the correlation between the percentage of necroptotic renal tubular epithelial cells and clinicopathologic parameters. In addition, the expression of angiotensinogen Ⅱ receptor (AT2R) in renal tissue and its correlation with the percentage of necroptotic renal tubular epithelial cells were analyzed.Results:With the development of CKD, the structural destruction of renal tubules in patients with CKD was gradually aggravated, and the renal tubules in the corresponding areas were atrophied, accompanied by worsening interstitial fibrosis. The adjacent renal tubules were focally dilated and numerous protein tubules were seen in the tubules. Importantly, renal tubular injury score in second and third stage of CKD was significantly higher than that in control group (both P<0.01). TUNEL+RIP3 immunofluorescence staining results showed that the percentage of TUNEL/RIP3 double positive renal tubular epithelial cells (necroptotic renal tubular epithelial cells) in renal tubules of the second and third stage of CKD was higher (all P<0.01). Immunohistochemical results showed that RIP3, MLKL and AT2R proteins were mainly expressed in cytoplasm of renal tubular epithelial cells, and the expression of RIP3, MLKL and AT2R in renal tubular epithelial cells was higher in the second and third stage of CKD patients (all P<0.05). Pearson correlation analysis showed that the percentage of necroptotic renal tubular epithelial cells was positively correlated with blood urea nitrogen ( r=0.514, P=0.003), serum creatinine ( r=0.507, P=0.019), serum cystatin C ( r=0.571, P=0.026), serum uric acid ( r=0.592, P=0.008), renal tubules injury score ( r=0.901, P<0.001), renal interstitial fibrosis index ( r=0.700, P=0.001) and the expression of AT2R protein in renal tissue ( r=0.715, P=0.001). Conclusions:As CKD progresses, necroptosis of renal tubular epithelial cells in CKD patients occurs. The necroptotic cell death may be an important factor leading to renal tubular epithelial cell excessive death and the progression of chronic kidney injury. Furthermore, necroptosis of renal tubular epithelial cells may be related to the high expression of AT2R in kidney tissue.

Objective:To analysis the incentive level of family doctors in primary medical and health institutions in Beijing, and to explore its influencing factors, so as to provide references for promoting family doctors′ contract service.Methods:From October to December 2021, 40 family doctors were randomly selected from 135 urban community health service centers in 8 districts of Beijing, and a survey was conducted on basic demographic information, institutional organizational capacity evaluation, and family doctor incentive level evaluation (including four dimensions of work value, organizational environment, personal development, and reward compensation), and the influencing factors of family doctor incentive level was analyzed. Chi-square test and Pearson correlation analysis were used for univariate analysis, and multiple linear regression analysis was used for multivariate analysis.Results:A total of 4 568 family doctors were included, and the score of family doctors′ incentive level was 3.75±0.81, among which the work value score was the highest(3.89±0.77), followed by the organizational environment score(3.69±0.92) and personal development score(3.75±0.90), and the lowest score was reward(3.75±0.90). Age, education, professional title, working years and average total working hours per week negatively affected the incentive level( P<0.05), while the average monthly income, the frequency of attending training and further study, and the organizational ability of the organization positively affected the incentive level( P<0.05). Conclusions:The overall incentive level of family doctors in primary medical and health institutions in Beijing needed improvement, and there were many factors that affect the incentive level of family doctors. It was recommended to appropriately increase the salary and benefits of family doctors, reasonably arrange the workload of family doctors, strengthen the training mechanism of family doctors, and strengthen the organizational capacity building of primary medical and health institutions.

Objective To formulate a pharmaceutical service pathway to standardize the pharmacists'whole process of pharmaceutical services for breast cancer patients in medical institutions,promote the standardization of pharmacists'work and improve the rationality of drug use for breast cancer patients in medical institutions.Methods The editorial committee aimed at several challenging problems in the whole process of pharmaceutical services for breast cancer patients in medical institutions through systematic search,referring to the latest domestic and international guidelines and expert consensus of breast cancer and under the relevant drug administration regulations in China,collected and sorted out the professional opinions of doctors,pharmacists,and methodological experts,developed questionnaires and held two rounds of expert argumentation meetings,and finally screened out the most valuable results.The whole process management pathway of pharmaceutical care for breast cancer patients was formulated,and the referral principles of hospitals at different levels and the contents of pharmacist training and assessment were clarified.Results The whole process management pathway of pharmaceutical services for breast cancer patients was developed,including information collection,analysis,evaluation,development implementation of intervention plans,and follow-up.Conclusion This pharmaceutical service pathway can standardize and guide pharmacists in hospitals at different levels to carry out pharmaceutical services for breast cancer patients,achieve the whole process of monitoring drug use,and ensure rational drug use and treatment effectiveness for patients.

In January 2023,the American Heart Association(AHA)released A Scientific Statement:Cancer Therapy Related Hypertension,provided an overview of the mechanisms and clinical management of anticancer therapy related hypertension.Contemporary anticancer drugs are mostly at the expense of cardiovascular toxicities,one of the most common side effects is hypertension,especially vascular endothelial growth factor inhibitors,as well as tyrosine kinase inhibitors and proteasome inhibitors.Cancer therapy related hypertension is often dose limiting,and is usually reversible after interruption or discontinuation of treatment.The exact molecular mechanisms underlying hypertension are unclear,recent discoveries indicate an important role for decreased nitric oxide,increased endothelin-1,endothelial dysfunction,increased sympathetic outflow,and microvascular rarefaction.Based on the International Cardio Oncology Society(IC-OS),this article provides an interpretation of the diagnosis and management of hypertension related to cancer treatment.Insufficient evidence exists supporting an antihypertensive medication strategy specific to patients with anticancer therapy induced hypertension,therefore,antihypertensive management should follow current guidelines for the general population..Multidisciplinary cooperation is needed to optimize management to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.

To provide prevention and control strategies of occupational exposure risks to cytotoxic drug in medical institutions， improve the awareness of protection among medical staff，and reduce potential occupational exposure risks，the Guidelines for the Prevention and Control of Occupational Exposure Risk to Cytotoxic Drugs in Medical Institutions is developed. Based on the World Health Organization Guidelines Development Manual，the exposure risk issues of the cytotoxic drug collected from the time that it entered the hospital to the several stages after delivery to hospital，such as transportation，receipt，storage，unpacking，dispensing，use of finished products，and waste disposal. Delphi method is used to construct identification of clinical issues，and evidence-based research method is used to develop relevant evidence. Quality evaluation is conducted by using the recommended GRADE method. The consensus is reached on the recommendation opinions and evidence levels through expert consensus method. By combining engineering controls，administrative controls and personal protective equipment at different levels，a graded control approach is established. A total of 37 clinical issues are identified，resulting in 36 recommendations. This guideline provides reference and supplementation for the formulation of cytotoxic drug prevention and control measures in medical institutions.

In order to strengthen the supervision of the use of drugs in hospitals，the Sichuan Academy of Medical Sciences· Sichuan Provincial People’s Hospital took the lead in compiling the Principles for the Rational Use of National Key Monitoring Drugs （the Second Batch） with a number of experts from multiple medical units in accordance with the Second Batch of National Key Monitoring Rational Drug Use List （hereinafter referred to as “the List”） issued by the National Health Commission. According to the method of the WHO Guidelines Development Manual， the writing team used the Delphi method to unify expert opinions by reading and summarizing the domestic and foreign literature evidence of related drugs， and applied the evaluation， formulation and evaluation method of recommendation grading （GRADE） to evaluate the quality of evidence formed， focusing on more than 30 drugs in the List about the evaluation of off-label indications of drugs， key points of rational drug use and key points of pharmaceutical monitoring. It aims to promote the scientific standardization and effective management of clinical medication， further improve the quality of medical services， reduce the risk of adverse drug reactions and drug abuse， promote rational drug use， and improve public health.