Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

OBJECTIVE To investigate the job mo bility of cl inical research coordinators （CRCs） and clinical research associates（CRAs）in Chongqing ，and to explore the feasible methods to improve the job stability of CRCs and CRAs. METHODS Questionnaire survey was conducted to investigate the job mobility of 200 CRCs and CRAs working in 22 drug clinical trial institutions of Chongqing. The contents included basic information ，job mobility ，and reasons for mobility. RESULTS & CONCLUSIONS Totally 178 valid questionnaires were recovered ，with an efficient recovery rate of 89.00％，of which 110 were recovered from CRCs and 68 were recovered from CRAs. Among the surveyed CRCs and CRAs ，the age distribution was mainly 20-30 years old ，accounting for 87.27％ and 82.35％ of the respective population respectively. The overall educational degree of CRAs were slightly higher than those of CRCs. The majors and previous work experience were mainly related to medicine ；the proportion of other non-medicine-related professions who switched to CRCs was higher than that of CRAs. Totally 88.18％ had CRC working experience within 3 years；after having 1-＜3 years of work experience ，50.00％ had worked in 2 or more work units. Totally 64.70％ had CRA working experience within 3 years；after having 1-＜3 years of work experience ，70.37％ had worked in 2 or more work units. CRCs handled 5.38 items of clinical trials and completed 1.22 items on average ；CRAs handled 7.47 items and completes 2.04 items on average. Main reasons of CRCs and CRAs for job-hopping included low salary below expectations，few promotion opportunities ，and too much workload ，accounting for 83.64％/80.88％，45.45％/39.71％，31.82％/ 26.47％，respectively. As an important part of clinical trials ，CRCs and CRAs had high job mobility. It is suggested to establish a unified industry standard ，standardize the management rights and responsibilities of CRCs and CRAs ，optimize the working mode of CRCs and CRAs ，and improve professional identity and sense of belonging ，so as to improve the job stability of relevant

【Objective】 To study the status and conduct effect evaluation of blood donation recruitment of blood services in Chongqing, and explore its influencing factors, so as to provide reference for the regional homogenization of blood services in Chongqing. 【Methods】 19 blood services in Chongqing were investigated by questionnaire in terms of the input in human resources and funds, recruitment methods, document construction and effect evaluation. The statistical analysis was conducted. 【Results】 The average number of blood donors per 1 000 population in 19 blood services in Chongqing was 9.35±3.35. Among the 19 blood services, blood inventory warning occurred in 18, 6 of them reached Level 2 and 1 of them was Level 1. The number of blood donations per 1 000 population in blood banks with no more than 5 recruits or with less than 100 000 yuan/year recruitment fund was significantly lower than that in blood banks with more than 5 recruits or with more than 100 000 yuan/year recruitment fund(P<0.05). SMS and telephone recruitment were most commonly used in blood donation recruitment. Most blood banks have established corresponding system documents, but only one has established the method to evaluate the effect of blood donation recruitment. 【Conclusion】 The number of blood donations per 1 000 population in 19 blood services in Chongqing varies greatly, and the pressure of blood inventory warning is widespread. The input of human resources and financial fund have a certain impact on the number of blood donations per 1000 population, but not the alone factor. The recruitment method is a little bit more on the traditional side, and the blood donation recruitment and efficacy evaluation is in lack of documentary supporting. Regional homogenization should be achieved by integrating the resources of blood services, establishing the document framework of blood donation recruitment and effect evaluation, clarifying the evaluation content and unifying the evaluation standard.

Objective:To explore the risk factors of hypopituitorism after aneurysmal subarachnoid haemorrhage (aSAH) in the acute phase and analysis the effect of hypopituitorism on prognosis.Methods:Patients with aSAH that were diagnosed and treated in China-Japan Union Hospital from Sep. 2017 to Sep. 2018 and undergoing pituitary function evaluation within 3 to 7 days were retrospectively analyzed. 72 patients were enrolled, including 31 males and 41 females. The average age was 50.1 years old (36-71) . The WFNS gradings were Ⅰ, 24; Ⅱ, 20; Ⅲ, 15; Ⅳ, 10; Ⅴ, 3. The Fisher gradings were 2, 21; 3, 38; 4, 13. Acute hydrocephalus happened in 13 cases. Aneurysm located in the Willis circle in 56 cases and not in the Willis circle in 16 cases. 37 cases were treated by microsurgical clipped and 35 cases were treated by embolism. Patients with hypocortisolism were treated by hydrocortisone replacement, and patients with hypothyroidism were given levothyroxine replacement therapy. Patients were followed up at 3 months and their recovery was evaluated by GOS score.Results:Hypopituitorism was detected in 34 patients; the incidence of hypopituitorism was 47.2%. There was no significant correlation between the occurrence of hypopituitorism and age, gender, and hydrocephalus ( P>0.05) . Patients with WFNS grade ≥Ⅳ, Fisher grade 4, aneurysm located in the Willis circle, and treated by clipping were more likely to undergo hypopituitorism. The proportion of patients with good recovery (GOS ≥4) in the hypopituitorism group was smaller than that in the normal pituitary function group at the 3-month follow-up. Conclusions:Patients with WFNS grade ≥Ⅳ, Fisher grade 4, aneurysm located in the Willis circle, and treated by clipping are more likely to undergo hypopituitorism. Hypopituitorism in acute stage affects the prognosis of aSAH patients. Patients with hypocortisolism and hypothyroidism should be treated actively.

Objective:To explore the clinical features, diagnosis and treatment of hypopituitorism after severe traumatic brain injury (TBI) in acute phase.Methods:Twenty-four patients with hypopituitorism after severe TBI that were diagnosed and treated in China-Japan Union Hospital from Jan. 2017 to Sep. 2018 were retrospectively analyzed.Results:Pituitary function was evaluated between 3 to 7 days after TBI, and hypopituitorism was detected in 15.2% (24/158) of patients with severe TBI. The average age of the 24 patients was 35.8 (range from 18 to 65) years, and the median GCS score on admission was 5.6 (range from 3 to 8) . The pituitary endocrine axis was involved as follows: hypofunction of pituitary-adrenal in 9 cases, hypofunction of pituitary-thyroid axis in 7 cases, hypofunction of pituitary-thyroid axis and pituitary-adrenal axis in 6 cases, hypofunction of growth hormone axis in 1 case and pituitary-gonad axis in 1 case. Hydrocortisone replacement was carried out in patients with hypofunction of pituitary-adrenocortical axis, and patients with hypofunction of pituitary-thyroid axis were given levothyroxine replacement therapy. All patients were followed up at 3 months after injury. Among the patients with pituitary-thyroid axis hypofunction, 61.5% (8/13) returned to normal. The pituitary-adrenocortical axis function returned to normal in 40% (6/15) patients with pituitary-adrenocortical axis hypofunction. Both the function of the growth hormone axis and the pituitary-gonad axis returned to normal.Conclusions:It is not uncommon for severe TBI patients to be complicated with hypopituitorism at early stage, which should be paid enough attention. Assessment of pituitary function at early stage can help to screen out the patients with severe adrenocortical hypofunction and hypothyroidism. Hormone replacement treatment should be carried out as early as possible, which has important significance for improving the prognosis of severe TBI patients.

Hypopituitorism is not uncommon in patients with aneurysmal subarachnoid hemorrhage (aSAH) . It can happen both in acute and chronic stages of aSAH. There are different clinical features of hypopituitorism happened in acute and chronic stages. In the acute stage, pituitary-adrenocortical axis dysfunction is of the most clinically significant, which can cause adrenal crisis. Growth hormone deficiency and pituitary-adrenocortical axis dysfunction are the two most common endocrine deficits in the chronic stage, symptoms include fatigue, decreased exercise capacity, cognitive impairment and decreased libido et al. The mechanism and risk factors of hypopituitorism are still unclear. The function of pituitary-adrenal axis should be paid attention for patients with aSAH during the acute phase. If patients manifest symptoms related to hypopituitorism during the chronic stage, comprehensive evaluation of pituitary function should be carried out. The diagnosis of hypopituitorism should be based on basic hormone level and corresponding stimulation test. Hypocortisolism in the acute phase of aSAH should be treated with glucocorticoid because of its potential contribution to the morbidity and mortality. Hypopituitorism occurred in the chronic phase of aSAH may have lasting effect on cognition and life quality, and hormone replacement should be carried out once the diagnosis be confirmed.

Hypopituitorism is a common complication of traumatic brain injury (TBI),which can happen both at acute and chronic stages after TBI.There are different clinical features of hypopituitorism happened at acute and chronic stages.At acute stage,dysfunction of pituitary-adrenal cortical axis is of the most clinical significance,which can cause hypotension,hypoglycemia,hyponatremia and lead to life-threatening complications.Growth hormone deficiency and hypogonadotropic hypogonadism are the two most common endocrine deficits at chronic stage.Symptoms of hypopituitorism at chronic stage include fatigue,cognitive impairment,decreased exercise capacity,decreased libido and so on.Assessment of pituitary function should be carried out for patients with moderate to severe TBI during the acute phase,focusing on the function of pituitary-adrenal axis.If patients manifest symptoms related to hypopituitorism during chronic stage,comprehensive evaluation of pituitary function should be carried out.The diagnosis of hypopituitorism should be based on basic hormone level and corresponding stimulation test.Hypofunction of pituitary-adrenal cortical axis in the acute phase of TBI should be treated with glucocorticoid immediately because of its potential contribution to the acute morbidity and mortality.Severe hypofunction of pituitary-thyroid axis should also be treated with thyroxine replacement.Most growth hormone deficiency and hypofunction of pituitary-gonadal axis occurred in the acute phase could be improved by themselves with time migration,so there is no need to be treated in this phase.Hypopituitorism occurred in the chronic phase of TBI may have lasting effect on cognition and life quality.Hormone replacement should be carried out once the diagnosis is confirmed.

Abnormal liver function in pregnancy is a common clinical problem in the department of obstetrics and liver disease, but its severity can cause danger to the life of the mother and fetus. Therefore, the different cause of abnormal liver function in pregnancy should be assessed accurately in order to take early intervention measures. Moreover, it is necessary to comprehensively evaluate the situation of both mother and fetus to obtain the optimal treatment effect for abnormal liver function caused by different types of pregnancy-related liver diseases.

OBJECTIVE: To investigate the protective effect of DSM17938 strain against oxidative stress in a neonatal mouse model of necrotizing enterocolitis (NEC) and explore the possible mechanism. METHODS: Ninety-six 10-day-old neonatal C57BL/6J mice were equally randomized into control group, NEC group, and NEC+ group. The pathological changes of the ileocecal intestinal tissue were evaluated with HE staining and double-blind pathological scoring. The mRNA and protein expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the intestinal tissues were detected using quantitative real-time PCR and ELISA, respectively. Colorimetric assays were used to determine the activity of superoxide dismutase (SOD) and its inhibition rate, malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and GSSG/ GSH ratio. RESULTS: Compared with those in the control group, the neonatal mice in NEC group showed significant weight loss ( < 0.05), obvious intestinal injury, increased pathological scores ( < 0.05), increased expressions of TNF-α and IL-1β mRNA and proteins ( < 0.05), decreased SOD activity and inhibition rate, decreased GSH, and significantly increased MDA, GSSG, and GSSG/GSH ratios ( < 0.05). Treatment with obviously decreased the pathological scores, expressions of TNF-α and IL-1β ( < 0.05), MDA, GSSG, and GSSG/GSH ratio ( < 0.05), and significantly increased SOD activity, its inhibition rate, and GSH level in the mice with NEC, but the survival rate was not significantly different between NEC and -treated groups ( > 0.05). CONCLUSIONS DSM17938 can offer protection against NEC in mice by reducing oxidative stress and increasing antioxidant capacity of the intestinal tissue to suppress intestinal inflammations.

OBJECTIVE： To summarize the problems and countermeasures which the construction of drug clinical trial institutions face after China Food and Drug Administration （CFDA） join in ICH， and its effects on clinical study management in China. METHODS： Combined with the experience on Good Clinical Practice （GCP） in our hospital during recent years， reviewing related content of ICH-GCP， the differences between China’s GCP （CFDA-GCP） and ICH-GCP， the problems faced by drug clinical trial institutions after joining in ICH， and the thinking of China’s clinical research were discussed. RESULTS & CONCLUSIONS： There were differences between CFDA-GCP and ICH-GCP in the management concept of clinical drug trials， the structure and function of ethical committees， the protection of the rights and interests of subjects， the choice of researchers and research institutions， management requirements of experimental drugs and the management of documents and data. After joining in ICH， the current organization and management structure， system and standard operating procedures， ethics committee， GCP training and continuing education， professional quality control system， experimental drug management， data management and information system construction and upgrading， clinical research coordinator management and other aspects of the drug clinical trial institutions were far from the requirements of ICH. The standardization of drug clinical trial institutions in China can be further promoted by revising regulations and guidelines， formulating standard operating procedures in line with ICH-GCP， building standardized ethics committees， implementing GCP training and continuing education， improving quality control system and drug management in clinical trials， strengthening hardware and software construction and clinical coordinator management， etc. At the same time， problems such as fewer full-time personnel and weak implementation of the system can be improved by strengthening project management， improving the quality of employees and building normal cross-regional cooperation.