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 clinical characteristics, differential diagnosis, treatments and prognosis of facial nerve hemangioma and schwannoma at genicular ganglion, so as to provide reference for clinical diagnosis and treatments of facial nerve tumor at genicular ganglion.Methods:Clinical data of 13 patients with facial nerve tumors at genicular ganglion confirmed by postoperative pathology in the Ninth People′s Hospital affiliated to Shanghai Jiaotong University School of Medicine from March 2018 to April 2020 were retrospectively analyzed, including seven cases of hemangioma and six cases of schwannoma. There were eight males and five females. Their ages ranged from 20 to 65, with an average age of 40. The course of disease ranged from 3 to 118 months, with an average of 52 months. All the patients underwent preoperative HRCT of the temporal bone and facial nerve dynamic contrast-enhanced(DCE) MRI examinations. All the patients had detailed surgical procedures and at least one-year postoperative follow-up.Results:On HRCT of the temporal bone, (4/7) hemangioma at geniculate ganglion showed characteristic honeycomb appearance, while 6/6 schwannoma and 3/7 hemangiomas showed expansive bone changes. On DCE-MRI, geniculate ganglion hemangioma (7/7) showed characteristic "point-to-surface" enhancement, and schwannoma (6/6) showed characteristic "face-to-surface" enhancement. For five hemangioma-patients with HB-Ⅱ-Ⅳ before surgery, the facial nerve anatomy was completely preserved through transcanal endoscopic approach(TEA), and the facial nerve function improved one year after surgery (two cases of HB-I, two cases of HB-Ⅱ, and one case of HB-Ⅲ). For two patients, with preoperative facial nerve function HB-Ⅴ-Ⅵ, since their tumors was inseparable from the nerves, they were performed with facial nerve anastomosis during the surgery, and the facial nerve function was improved to HB-Ⅳ level one year after surgery. For six patients with meningioma whose facial nerve function was greater than or equal to HB-Ⅲ, based on the preoperative hearing level, the involved segments, and duration of facial paralysis, three of them were conducted surgeries through middle cranial fossa approach, one by translabyrinthine approach, and one via mastoid approach. Two patients among them with complete facial paralysis over three years preoperatively were not performed facial nerve anastomosis after total resections of the tumors, and there was no improvement in facial nerve function one year after surgery. Three patients underwent facial nerve anastomosis after total tumor resections, and their facial nerve function was HB-Ⅲ in one patient, HB-Ⅳ in two patients one year after surgery. One patient (preoperative HB-Ⅲ) had a normal hearing level preoperatively, and the tumor involved the labyrinth segment. To protect the hearing, partial tumor was resected through the middle cranial fossa approach, and facial nerve function improved to HB-Ⅱ one year after surgery.Conclusions:Temporal bone HRCT combined with DCE-MRI are useful for the differential diagnosis of hemangioma and schwannoma at geniculate ganglion and provide references for preoperative clinical decision makings. It is extremely necessary to select the appropriate surgical approach based on the patient′s hearing and involved segments. For geniculate ganglion hemangioma, early surgery can improve the possibilities of anatomical integrity of facial nerve, thereby improving facial nerve function postoperatively.TEA is a kind of surgical method worth consideration, with the characteristics of minimally invasive, favorable postoperative features, and so on. For schwannoma, one-stage functional reconstruction of the facial nerve is recommended during the resection of the tumors because of the inevitable damage to the anatomical integrity of the facial nerve.

Objective: The incidence and distribution of positional deformities(PD)were studied by measuring cranial types of infants aged 0-6 months of 3 hospitals in Chongqing, and the recommended values of local PD were discussed. Methods: Data of 3 406 infants with 0-6 months head size measurements were collected from the Second Affiliated Hospital of Army Military Medical University, Yongchuan Maternal and Child Health Care Hospital and Wanzhou Maternal and Child Health Care Hospital from September 1, 2017 to August 31, 2018, cranial vault asymmetry(CVA)and cranial index(CI)were calculated.According to different age groups, observe the distribution of cranial types, and use the current international common diagnostic criteria to understand the incidence of cranial abnormalities, and analyze the distribution of percentile values of CVA and CI in infants in Chongqing. Results: According to the current international standard diagnosis of PD, the incidence of simple brachycephaly was the highest(39.9%)in the overall cranial abnormalities of infants, followed by brachycephaly with plagiocephaly was the second(36.1%), simple plagiocephaly was the lowest(6.9%), and normal cranial type only accounted for 17.1%.The detection rates of plagiocephaly(36.9%)and brachycephaly(67.0%)were the lowest in the 0-2 months group, and the highest in the 3-4 months group(47.3%/83.3%), and then decreased in the 5-6 months group(46.6%/80.2%). Conclusion The basic values of cranial type measurement of full-term infants in chongqing were significantly different from international reports, mainly due to the large CI value.The general international diagnosis standard for positional deformities do not conform to Chinese infants.We suggest that the reference value for positional deformities in this region is as follows: CVA≥0.4 cm is abnormal, of which 0.4 cm≤CVA<0.6 cm for mild plagiocephaly, 0.6 cm≤CVA<1.0 cm for moderate plagiocephaly, CVA≥1.0 cm for severe plagiocephaly; 82%≤CI≤91% is abnormal, of which 91%≤CI<94% for mild brachycephaly; 94% ≤CI<99% for moderate brachycephaly; CI≥ 99% for severe brachycephaly.CI≤82% is scaphocephaly.

OBJECTIVETo research the central molecular mechanism of gastric motility in functional dyspepsia (FD) rats treated with electroacupuncture (EA) at and points of stomach.

METHODSA total of 30 SD rats were randomized into a blank group, a model group, a Zhongwan+Weishu group, a Weishu group and a Zhongwan group, 6 rats in each group. FD rats were established by moderate clipping tail infuriation and irregular feeding except in the blank group. EA was used at "Zhongwan"(CV 12),"Weishu"(BL 21), and"Zhongwan"(CV 12) +"Weishu"(BL 21) in the corresponding groups for 7 days, once a day, and 20 min a time. No intervention was used in the blank and model groups. Grabbing and fixation were applied in the model group. Gastric antrum motion range and frequency were recorded by gastrointestinal pressure transducer. The expression of subunit NR1 of N-methyl-D-aspartate recepter (NMDAR) in dorsal motor nucleus of the vagus (DMV) was determined by Western blotting. The content of serum nitric oxide (NO) was measured by ELISA.

RESULTSCompared with the blank group, the gastric antrum motion range and NR1 in the DMV decreased and the serum NO content increased in the model group (all <0.05). Compared with the model group, the gastric antrum motion range and NR1 in the DMV increased and the serum NO content decreased in the three EA groups (all <0.05). Compared with the Zhongwan and Weishu groups, the gastric antrum motion range and NR1 in the DMV increased in the Zhongwan + Weishu group (all <0.05). Compared with Zhongwan + Weishu and Zhongwan groups, the expression of NO in the Weishu group decreased (both <0.05). The gastric antrum motion frequency among the 5 groups had no statistical significance (all >0.05).

CONCLUSIONEA at the and points can regulate the gastric motility in FD rats which may be by modulating the activity of NMDAR in the central DMV region, thus regulating the serum NO content.

Acupuncture Points ; Animals ; Dyspepsia ; therapy ; Electroacupuncture ; Gastrointestinal Motility ; N-Methylaspartate ; metabolism ; Nitric Oxide ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stomach ; Vagus Nerve ; metabolism

Telotristat ethyl is a peripheral tryptophan hydroxylase (TPH) inhibitor for the treatment of carcinoid syndrome. Telotristat ethyl inhibits TPH,thereby reducing the production of serotoin(5-HT) and the daily bowel movement. Pharmacology, pharmacokinetics,clinical studies and safety of telotristat ethyl were reviewed in the paper. Telotristat ethyl has become a novel treatment option for carcinoid syndrome patients. Telotristat ethyl is well tolerated with low incidence of side effects.

OBJECTIVE:To establish HPLC fingerprint of stir-baked Manis pentadactyla.METHODS:HPLC method was conducted.The determination was performed on Capcell Pak Mg Ⅱ S5 C18 column with mobile phase consisted of acetonitrile-0.1％ phosphoric acid solution (gradient elution) at the flow rate of 0.8 mL/min.The detection wavelength was set at 275 nm,and column temperature was 30 ℃.The sample size was 10 μL.Using oxyphenylaminopropionic acid as reference,HPLC chromatograms of 11 batches of medicinal materials were determined.TCM Chromatogram Fingerprint Similarity Evaluation System (2004 A edition) was used for common peak identification and similarity evaluation.RESULTS:There were 23 common peaks in 11 batches of stir-baked M.pentadactyla,with similarity＞0.90.After validation,HPLC chromatograms of 11 batches of medicinal materials were in good agreement with control fingerprints.CONCLUSIONS:Established HPLC fingerprint can provide reference for the identification and quality evaluation of stir-baked M.pentadactyla.

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

BACKGROUND:Currently, modified laminoplasty with C7 spinous process and muscle attachment points reserved and C2, C7 decompressive laminectomy can reconcile both ful decompression and structure stability. With early isometric neck muscle exercise, it can enhance cervical dynamic and static force balance and maintain the stability of the cervical spine.
OBJECTIVE:To investigate the clinical effects of modified cervical laminoplasty with postoperative isometric neck muscle exercise on cervical spondylotic myelopathy patients.
METHODS:114 patients with cervical myelopathy were separately performed traditional cervical laminoplasty (control group), modified cervical laminoplasty (modified group), modified cervical laminoplasty, and neck muscle isometric exercise (combined group). Fol ow-up was conducted for 24 months.
RESULTS AND CONCLUSION:(1) Cervical Japanese Orthopaedic Association score, cervical Neck Disabilitv Index scores and the incidence of axial symptoms:There was no significant difference in the Japanese Orthopaedic Association score of three groups at 6, 12 and 24 months after surgery. At 6, 12 and 24 months after surgery, Neck Disability Index scores and constituent ratio of axial symptoms were better in the modified group than the other groups (P<0.05). (2) Results show that modified cervical laminoplasty with isometric neck muscle exercise can get better clinical results in the treatment of cervical myelopathy.

Pharmacology , pharmacokinetics , clinical study and safety of enzalutamide in the treatment of castration-resistant pros-tate cancer (CRPC) were reviewed in the paper.Enzalutamide, a pure second-generation androgen receptor antagonist , can inhibit multiple points in the androgen receptor signaling pathway , including the inhibition of androgen binding to the androgens receptor , nu-clear translocation of the androgens receptor complex and binding of the androgens receptor complex to deoxyribonucleix acid ( DNA) . The phase 3 clinical trials have revealed that enzalutamide is effective to delay the progression of metastatic CRPC , reduce the prostate-specific antigen (PSA) levels, decrease the progression time of PSA and prolong the overall survival time and the time of first skeletal -related events .Enzalutamide has become a novel treatment option for CRPC patients .Enzalutamide is well tolerated with low incidence of side effects .

OBJECTIVETo investigate the regulatory effects of miR-18a on chemotherapeutic sensitivity of leukemia cell HL-60 to VP-16 and VCR, and explore its molecular mechamism.

METHODSThe HL-60 PC DNA3.1-miR-18A cell line with stably overexpressing miR-18a was constructed and their sensitivity to VP-16 and VCR was detected. The luciferase reporter vector of ATM 3'UTR region was constructed and the targeting effect of miR-18a on ATM was identified. The expression level of ATM in HL-60 cells overexpressing miR-18a was detected by Western blot. The seusitivity of HL-60 cells with knockdown of ATM to VP-16 and VCR was detected by CCK-8 method. The ATM expression level in HL-60 cells with stably overexpression miR-18a after transfection of miR-18a inhibitor was detected by using Western blot and the sensitivity changes of these HL-60 cells to VP-16 and BCR were detected.

RESULTSAfter overexpression of miR-18a, the viability of HL-60 cells treated with VP-16 and VCR of same concentration decreased; the detectiion of luciferase activity showed that the miR-18a could inhitit activity of luciferase reporter vector of ATM; the expression level of ATM in HL-60 cells was down-regulated after transfection with miR-18a; the cell viability decreased when HL-60 cells were treated with VP-16 and VCR after knockdown of ATM; the expression level of ATM was up-regulated and the cell viability decreased when HL-60 cells were treated with VP-16 and VCR after transfection with miR-18a inhibitor.

CONCLUSIONThe miR-18a can regulated the sensitivity of leukemia HL-60 cells to VP-16 and VCR by targeting ATM.

Antineoplastic Agents ; Down-Regulation ; HL-60 Cells ; Humans ; Leukemia, Promyelocytic, Acute ; MicroRNAs ; Transfection ; Up-Regulation