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OBJECTIVE To explore the value of providing pharmaceutical service related to risdiplam in direct-to-patient （DTP） pharmacies. METHODS The follow-up data of spinal muscular atrophy （SMA） patients who purchased and used risdiplam from Shangyao Yunjiankang Yiyao Pharmacy （Shanghai） Co.， Ltd. from May 2021 to January 2023 were collected. The medication information， therapeutic efficacy and the occurrence of adverse events were retrospectively analyzed. RESULTS A total of 42 prescriptions were checked by pharmacists in the DTP pharmacies， and 7 prescriptions were found to be unreasonable （16.7%， 7/42）， which were corrected after the timely intervention. During the follow-up management， pharmacists replied to 4 patients （9.5%， 4/42） regarding medication consultation about medication requirements and adverse events. Two patients with type Ⅰ SMA experienced adverse events： one of them presented with fever and the other presented with skin dryness with darkening. Both of them were grade Ⅰ toxic reactions and generally did not require clinical treatment. Considering that the patient sustained low-grade fever for a long time， the pharmacist suggested symptomatic treatment under the guidance of the doctor. CONCLUSIONS Pharmacists in DTP pharmacies conducting follow-up management of risdiplam use for rare disease SMA patients can help promote rational， standardized medication for patients.
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Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED 50 of 18 μg. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management.
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PURPOSE@#To develop animal models of penetrating thoracic injuries and to observe the effects of the animal model-based training on improving the trainees' performance for emergent and urgent thoracic surgeries.@*METHODS@#With a homemade machine, animal models of lung injuries and penetrating heart injuries were produced in porcine and used for training of chest tube drainage, urgent sternotomy, and emergent thoracotomy. Coefficient of variation of abbreviated injury scale and blood loss was calculated to judge the reproducibility of animal models. Five operation teams from basic-level hospitals (group A) and five operation teams from level III hospitals (group B) were included to be trained and tested. Testing standards for the operations were established after thorough literature review, and expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Tests were carried out after the training. Pre- and post-training performances were compared. Post-training survey using 7-point Likert scale was taken to evaluate the feelings of the trainees to these training approaches.@*RESULTS@#Animal models of the three kinds of penetrating chest injuries were successfully established and the coefficient of variation of abbreviated injury scale and blood loss were all less than 25%. After literature review, testing standards were established, and expert questionnaire results showed that the scientific score was 7.30 ± 1.49, and the feasibility score was 7.50 ± 0.89. Post-training performance was significantly higher in both group A and group B than pre-training performance. Post-training survey showed that all the trainees felt confident in applying the operations and were generally agreed that the training procedure were very helpful in improving operation skills for thoracic penetrating injury.@*CONCLUSIONS@#Animal model-based simulation training established in the current study could improve the trainees' performance for emergent and urgent thoracic surgeries, especially of the surgical teams from basic-level hospitals.
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Animals , Swine , Reproducibility of Results , Wounds, Penetrating/surgery , Thoracotomy , Thoracic Injuries/surgery , Hemorrhage , Models, AnimalABSTRACT
To study the reversal effect of docetaxel (DTX) and verapamil (VRP) liposome (DTX-VRP LP) on multidrug resistance of human breast cancer chemotherapy, DTX-VRP LP was prepared by thin film dispersion method. The particle size and zeta potential were measured by laser particle sizer. The drug loading, entrapment efficiency and the cumulative release rate of liposomes in phosphate buffer saline solution (PBS) with pH 7.4 and 6.8 were determined by ultrafiltration and dynamic dialysis, respectively. With DTX resistant human breast cancer cells (MCF-7/DTX) to study on the pharmacodynamics of liposomes in vitro and in vivo. The animal experiments were approved by the Animal Research Ethics Committee of School of Medicine of Shanghai Jiao Tong University (No. 2019-06-172). The average particle size and zeta potential of DTX-VRP LP were about 140.9 nm and -28.7 mV, respectively. The entrapment efficiency and drug loading of DTX and VRP in DTX-VRP LP were (81.7 ± 3.9)%, (2.9 ± 0.3)% and (59.6 ± 0.6)%, (1.6 ± 0.5)%, respectively. The cumulative release rate of the group of DTX-VRP LP was about 40% and 70% within 0-4 h in pH 7.4 and 6.8 PBS, respectively. It was slightly slower compared with other experimental groups. In vitro pharmacodynamics experiments, the value of IC50 of DTX solution, DTX LP and DTX-VRP LP were 3.19 ± 0.6, 1.46 ± 0.48 and 1.12 ± 0.33 μmol·L-1 on human breast cancer cells (MCF-7), respectively. The results showed the data was not much difference between the other groups and all experimental groups had strong cytotoxicity on MCF-7. However, on the MCF-7/DTX, the IC50 values of the other groups were greater than 10 μmol·L-1 while DTX-VRP LP group 7.4 ± 2.86 μmol·L-1. The results showed DTX-VRP LP had obvious cytotoxicity with the concentration dependent reversal of multidrug resistance (MDR) of breast cancer MCF-7/DTX cells (P<0.05), the other experimental groups had no effect on MCF-7/DTX cells. The inhibitory effect of MCF-7/DTX in vivo is consistent with that in vitro. In conclusion, DTX-VRP LP could reverse the MDR of MCF-7/DTX cells.
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OBJECTIVE：To investigate antitumor pharmaceutical care ability a nd the current status of direct to patient （DTP） pharmacy in China ，and to provide reference for building a quality evaluation system of DTP pharmacy which focuses on the pharmaceutical care. METHODS ：From Sept. to Dec. 2019， an electronic questionnaire survey was conducted amongpharmacists of all of 126 listed DTP pharmacies and involved wang_star@163.com education background ，professional knowledge sources andpharmaceutical care ability （such as prescription checking and E-mail：dujoan-88@163.com dispensing，medication consultation and guidance ，medication management，follow-up），pharmaceutical knowledge of antitumor medicine ，etc. DTP pharmacies in C hina were inspected on site ， and their pharmaceutical care management were evaluated ，and impression of on-site inspection were discribed with questionnaire survey. The current situation of oncology pharmaceutical care ability of DTP pharmacy in China was evaluated and corresponding suggestions were put forward. RESULTS ：A total of 400 questionnaires were sent out ，and 392 valid questionnaires were collected with recovery rate of 98.0％. The cancer pharmacists in DTP pharmacy were mainly from East China ，mainly in Jiangxi （73 persons，18.62％），Anhui（68 persons，17.35％）. The pharmacists were mainly junior college or below （229 persons，58.42％）， followed by undergraduate （158 persons，40.31％）. The working years were more than 5 years（241 persons，61.48％）. The majors were mostly pharmaceutics （123 persons，31.38％），followed by pharmacy （including pharmacology ）（81 persons， 20.66％）. The regular knowledge sources of pharmacists in DTP pharmacy included learning materials （302 person times ， 77.04％），textbooks（250 person times ，63.78％）and Wechat push （206 person times ，52.55％）；the latest knowledge sources included training courses （347 person times ，88.52％），Wechat push （211 person times ，56.38％）and academic conferences （162 person times ，41.33％）. The expected training methods included online video courses （344 person times ，87.76％）and offline courses（248 person times ，63.27％）. In terms of prescription checking and dispensing ，there were mainly problems such as incomplete medical documents and materials ；82.91％ and 64.54％ of pharmacists needed routine medical records and discharge summary，and 91.58％ of pharmacists took the doctor ’s handwritten prescription as the basis for dispensing new anti-tumor drugs ； pharmacists paid less attention to allergy history ，genetic history and ADR in the field of drug consultation and guidance. According to DTP pharmacists ，the difficulties in the process of drug treatment management included patient ’s ADR monitoring （239 person times，60.97％），evaluating the rationality of drug use （222 person times ，56.63％），making a complete drug use record （219 person times ，55.87％）. The main follow-up visits of pharmacists were telephone （334 person times ，85.20％）and dispensing site （313 person times ，79.85％）. And 333 pharmacists（84.95％）thought it was necessary to make an appointment for dispensing ；the score rates of professional knowledge examination of antitumor pharmacy for the respondents were 40.56％-84.69％. In the aspect of pharmaceutical care management ，the main points of deduction were drug evaluation ，content and process of drug treatment management，drug follow-up and record ，and the proportion of deduction was 93％，86％ and 64％ respectively. In the on-site inspection，it was found that the pharmacist had a single source of working knowledge ，did not fully grasp the contents of the evaluation forms such as ADR classification standard ，and prescription checking did not meet the requirements. CONCLUSIONS ： DTP pharmacy in China develops rapidly under the guidance of relevant policies ，but its pharmaceutical care is still in the basic stage，which is far behind the requirements of providing whole-course pharmaceutical care for patients. It is necessary to improve the professional service ability of DTP pharma
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Objective To analyze the risk factors affecting pre-eclampsia, to establish a pre-eclampsia risk assessment model, and to assess the risk of pre-eclampsia early. Methods A face-to-face questionnaire survey was conducted for all women who gave birth in the Department of Obstetrics, the First Hospital of Shanxi Medical University from March 2012 to September 2016. A total of 10 319 qualified questionnaires were collected to exclude 9 623 cases of other hypertensive diseases related to pregnancy. A total of 70% of the subjects were randomly selected as training samples to analyze the influencing factors of pre-eclampsia, and a Logistic regression model was established. The remaining 30% of the objects are used as test samples to verify the effect of the model. Results Logistic regression model was established with training samples. Logit P=-2.517-0.696×Pre-pregnancy lean +0.200 ×Pre-pregnancy overweight +0.944×Pre-pregnancy obesity -1.995×Residential in city -0.409×Folic acid supplemented before pregnancy +1.323×Twin and multiple pregnancy +1.708× History of previous pregnancy hypertension. Homer-Lemeshow test P=0.377. Model AUC=0.767 (95%CI:0.747-0.786, P<0.001). Using the test sample to verify the model, the model sensitivity was 81.68%, the specificity was 75.05%, the positive likelihood ratio was 3.27, and the negative likelihood ratio was 0.24. The test sample model AUC = 0.771 (95%CI=0.763-0.790,P<0.001). Conclusion This study establishes a simple and effective pre-eclampsia risk assessment model with controllable factors. The model has good fit and sensitivity and specificity.
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Objective To observe the effects of Jieduan Niwan Prescription on IL-6 and TNF-α in serum and hepatic tissue in acute-on-chronic liver failure rats (ACLF); To study the partial mechanism of the treatment for ACLF. Methods The ACLF rat model was established by using human serum albumin immuno-induced hepatic fibrosis followed with D-galactosamine and lipopolysaccharide joint acute attack. The SPF Wistar male rats were randomly divided into normal group, model group and Jieduan Niwan Prescription group, respectively. The Jieduan Niwan Prescription group was treated by Jieduan Niwan Prescription after the acute attack for 24 h, and the rats were sacrificed respectively at 5, 10 and 15 days after gavage administration. Transmission electron microscope was employed to observe the ultrastructural changes in liver cells and ELISA was used to detect the contents of IL-6 and TNF-α in serum and liver tissue, respectively. Results Compared with the normal group, the contents of serum and liver tissue IL-6 and TNF-α in model group increased at each time point. Compared with the model group, the contents of serum and liver tissue IL-6 and TNF-α decreased in Jieduan Niwan Prescription group, especially in 15 days. Under the transmission electron microscope, the changes of ultrastructure of liver tissue were observed. With the passage of time, the degree of hepatocyte injury in model group gradually increased, but decreased significantly in Jieduan Niwan Prescription group at each time point. Conclusion Jieduan Niwan Prescription can effectively reduce the levels of IL-6 and TNF-α in serum and liver tissue, reduce the degree of liver damage, and has a certain protective effect on the liver.
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Objective To investigate the effect of thrombin and hemoglobin on aquaporin (AQP) and the correlation between AQP and hydrocephalus.Methods Eighty-four clean grade healthy male SD rats were randomly divided into 3 groups:a control group,a thrombin group,and a hemoglobin group using the random number table method.A hydrocephalus model was induced by injecting isotonic saline (0.3 ml),thrombin (0.3 ml[10,U/ml]) and hemoglobin (0.3 ml[150 mg/ml]),respectively into the cisterna magna.According to the deficiency and complement way,each group maintained 24 rats.The relative area of the lateral ventricles,the expression of AQP1 and AQP4,and the correlation between AQP and the area of the lateral ventricles were observed at 1,3,7,and 14 d after molding.Results (1) Compared with the control group,both the thrombin group and hemoglobin group showed hydrocephalus at 1 ,3 ,7 and 14 d,and they were most obvious at 1 day (6.94±0.19% and 6.58±0.15% vs.3.40±0.13%,6.06±0.12% and 5.79±0.09% vs.3.55±0.15%,5.80±0.13% and 5.58±0.08% vs.3.78±0.18%,5.66±0.14% and 5.47±0.13% vs.3.52±0.18 %,respectively).There were significant differences (all P0.05);in the thrombin group and hemoglobin group,compared with those at 1 d,the expression levels of AQP1 and AQP4 at 3,7,and 14 d were significantly decreased (all P<0.01);compared with those at 3 d,AQP1 was decreased significantly at 7 and 14 d (P<0.05).The differences were statistically significant (P<0.05).(3) The relative expression levels of AQP1 (r=0.983,P<0.01) and AQP4 (r=0.987,P<0.01) in the thrombin group at each time point were positively correlated with the contralateral ventricular area;and the relative expression levels of AQP1 (r=0.964,P<0.01) and AQP4 (r=0.962,P<0.01) in the hemoglobin group at each time point were positively correlated with the contralateral ventricular area Conclusions After injecting thrombin and hemoglobin into subarachnoid space,it could cause the increased expression levels of AQP1 and AQP4 of ventricles and their surrounding areas.Thrombin and hemoglobin may be the important mediating factors of hydrocephalus after subarachnoid hemorrhage.
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Objective To analyze the correlation among 3 kinds of detection methods of routine microscopic examination,fluorescence PCR nucleic acid amplification and fungal color culture in the fungal detection of vaginal secretion.Methods The patients with suspected vaginitis treated in this hospital during 2014-2016 were selected.Each 500 cases of negative and positive vaginal secretion samples by microscopic examination were collected.The candida types were identified by using the fluorescence PCR nucleic acid amplification,then 100 samples with the positive results of fluorescence PCR nucleic acid amplification for detecting fungal were performed the fungal microbial culture to verify the accuracy rate of typing results.Results The Kappa value of consistency test between fluorescence PCR nucleic acid amplification and routine microscopic examination was 0.632,the consistency between them was poor.Among 500 positive samples of vaginal secretion detected by routine microscopic examination,382 cases (76.4 ％) of Candida albicans infection were detected by fluorescence PCR nucleic acid amplification,73 cases (14.6％) were Candida glabrata infection,10 cases (2.0 ％) were Candida tropicalis infection,3 cases (0.6 ％) were Candida albicans combined Candida glabrata infection and 32 cases (6.4 ％) were other fungal infection.Among 500 negative samples by conventional microscopic examination,152 positive cases were identified by fluorescence PCR nucleic acid amplification,including 130 cases of Candida albicans,16 cases of Candida glabrata and 6 cases of Candida tropicalis.There was no statistical significant difference in positive rate between the fluorescence PCR nucleic acid amplification and CHROMAgar rapid color method (x2 =0.131,P =0.936).Conclusion For the patients with clinical manifestations and negative microscopic examination results,it is recommended to conduct fluorescence PCR nucleic acid amplification rapid type identification or fungal culture identification.
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Objective To identify mutations of CACNA1A gene in a family with hemiplegic migraine.Methods Total genomic DNA was extracted from a family with 3 affected members and 1 000 healthy controls.The proband and his patient sister were subjected to exome sequencing.Ten family members including 3 patients were subjected to linkage analysis.The coding exons of the CACNA1A gene were amplified and sequenced in affected and normal individuals. Bioinformatics analysis were performed.Results A novel CACNA1A mutation was identified in the 3 patients.The nonsense mutation of A to G was detected at nucleotide 1168 ( c.1168A >G) which converted the Asn codon ( AAT) to Asp (GAT) in exon 8.Conclusion The mutation(N390D) detected in the present study is considered to result in the Chinese Hemiplegic migraine family.
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Objective To investigate the relationship between familial hemiplegic migraine (FHM ) with the mutation of CACNA1A gene .Methods Total genomic DNA of a family affected members and 1 000 normal controls was extracted for conduc‐ting the CACNA1A gene sequencing research and the bioinformatics analysis .Results The novel mutation site c .1168A>G of ex‐on located in CACNA1A gene led to Asn to be replaced with Asp (N390D) .Conclusion The mutation(N390D) of CACNA1A gene is a newly found novel pathogenic mutation lead to familial hemiplegic migraine .
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Objective:To optimize the extraction technology of compound Xiongdan capsules. Methods: The effects of water a-mount, decoction duration and decoction times on the water extraction technology were investigated by orthogonal design using the ex-tract derivation rate and the content of ginsenoside Rg1 , Re and Rb1 as the indices. Results:The optimal water extraction conditions for ginseng and Nidus vespa were as follows:decocting three times with 8-fold of water, and extracting for one hour each time. The extract was condensed until the relative density was 1.20(80-90℃), and then dried and crushed into fine powder. The other herbs were crushed into fine powder and screened by No. 5 meshes. The above powder was blended and well mixed with starch, and then packed into capsules. Conclusion:The optimized water extraction technology is stable, feasible and reproducible, which provide reference for industrial production.
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20 first mandibular premolars were randomly divided into 2 groups(n =10).The teeth in experimental group were treated by fi-ber main post in combination with auxiliary pile,in control group by single fiber main post,and then were restored by metal crown.They were fixed in universal testing machine.The fracture load(N)of experimental and control group was (846.50 ±40.33)and (437.90 ±41.15) respectively(P <0.01).
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This study was aimed to investigate the expressions of genes hoxb2 and hoxb4 after interference of the proliferation and differentiation of hematopoietic stem cells (HSC) to the erythroid progenitors (CFU-E) in vitro by using all-trans retinoic acid (ATRA). The cord blood was collected from 12 cases of fetal placenta umbilical vein and cultured by using culture technique of HSC in vitro. The proliferation and differentiation of HSC to CFU-E were interfered with 6 x 10(-8) mol/L of ATRA. The expression levels of genes hoxb2 and hoxb4 in blank control and ATRA groups were detected by FQ-RT-PCR on day 3, 7 and 10 of culture. The results showed that the expressions of genes Hoxb2 and hoxb4 were a little on day 3, obviously increased on day 7 and reached highest level on day 10 in 2 groups. The expression level of hoxb4 on day 3, 7 and 10 in blank control group was obviously higher than expression level of hoxb2. As compared with blank control group, the expressions of genes hoxb2 and hoxb4 in the ATRA group were significantly up-regulated. It is concluded that the genes hoxb2 and hoxb4 all expressed in process of proliferation and differentiation to erythroid progenitors, which suggests that hoxb2 and hoxb4 relate to erythroid hematopoiesis, and the hoxb4 has more great relevance to erythroid hematopoiesis as compared with hoxb2. The ATRA (6 x 10(-8) mol/L) can up-regulate the expression of hoxb2 and hoxb4 significantly.
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Female , Humans , Pregnancy , Cells, Cultured , Fetal Blood , Cell Biology , Gene Expression , Hematopoietic Stem Cells , Homeodomain Proteins , Genetics , Transcription Factors , Genetics , Tretinoin , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the association of the polymorphism of I181L, V183L and E237G in the high affinity immunoglobulin E receptor beta-chain (FcepsilonR1beta) with the susceptibility of childhood asthma and the serum total immunoglobulin E (IgE) level.</p><p><b>METHODS</b>The coding variants of I181L, V183L and E237G and the serum total IgE level were detected using amplification refractory mutation systemdouble ended arrowpolymerase chain reaction (ARMS-PCR) and double antibody sandwich ELISA respectively in 50 asthmatic children and 40 normal controls from Sichuan Province. The association of gene mutation with the susceptibility of asthma and the serum total IgE level was analyzed.</p><p><b>RESULTS</b>There were 5 cases of I181L mutation, 2 of V183L mutation, and 7 of E237G mutation in the Asthmatic group. There was no mutation in the Normal control group. The frequency of I181L and E237G mutation in the Asthmatic group were statistically higher than in the Normal control group (P < 0.01). The serum total IgE level in the Asthmatic subgroup with I181L mutation (2.837 +/- 0.407) or E237G mutation (3.044 +/- 0.419) was significantly higher than in the Asthmatic subgroup without gene mutation (2.156 +/- 0.638) and the Normal control group (1.348 +/- 1.291) (P < 0.05 or 0.01).</p><p><b>CONCLUSIONS</b>The polymorphism of Fc epsilonR1betaI181L and E237G is a susceptible gene of childhood asthma and closely associates with the increased serum total IgE level.</p>