OBJECTIVE:To provide suggestions for solving the problem of hospital pharmacy waiting time for medicine. METHODS:The definition and classification of the response time in hospital pharmacy dispensing process were introduced. The re-sponse time was considered to analyze the causes of waiting time for medicine in outpatient pharmacy and central pharmacy. The scheme for shortening the waiting time for medicine were put forward. RESULTS&CONCLUSIONS:The response time can be di-vided into 2 types,i.e. relative invariable and relative variable;the former results from hardware factor,system factor and other factors,and is relative stable and hardly changed;the latter results from that the speed of previous step is higher than that of next step,and can be changed by certain method,such as adjusting the proportion of manpower allocation,adjusting manpower tempo-rarily. Based on the concept of response time,the essence of waiting time for medicine can be understood accurately and deeply, and countermeasure can be found out fundamentally and used for other steps as prescribing prescription.

ObjectiveTo investigate the clinical epidemiology of intrahepatic cholelithiasis in Guangxi area. MethodsAn retrospective analysis was made on 8?585 cases of intrahepatic cholelithiasis proved by exploration in a period of 19 years. Data were collected and analyzed by computer PEMS.ResultsThe intrahepatic cholelithiasis accounted for more than one third of all biliary stone disease treated during the same period. The prevalence of intrahepatic cholelithiasis in peasants victim increased from 23.4% out of all gall stones in a period of 1981～1985 to 55.8% between 1991～1999. The constituent ratio of intrahepatic lithiasis in males was nearly the same to that in females. The peak age range of patients with intrahepatic lithiasis was 31～40, and the mortality was the highest among all biliary stone disease. ConclusionsIntrahepatic cholelithiasis is by no means a vanishing disease,especially in rural area.

Objective To investigate the effect of intrathecal (IT) transplantation of different quantities of neural stem cells (NSCs) on neuropathic pain (NP) in rats.Methods Eighty-four adult pathogen-free male SD rats weighing 150-180 g were randomly divided into 7 groups ( n = 12 each) : group sham operation (S group) , NP group, NP+ NSCs 103 , 104 , 105 , 106 , 107 groups (N1-5 groups) . NP was induced by partial transection of right sciatic nerve. NSCs were transplanted into subarachnoid space in N1-5 groups. Paw withdrawal threshold to mechanical stimulation (MWT) and paw withdrawal latency to nociceptive thermal stimuli (TWL) were measured at 1 day before (baseline) and 1, 3, 7, 14 and 21 days after operation. Brain derived neurotrophic factor ( BDNF) expression in spinal dorsal horn and dorsal root ganglia (DRG) was detected by immuno-histochemistry and RT-PCR on the 7th and 21st day after operation. Results Partial transection of the sciatic nerve gradually reduced MWT and TWL after operation starting from day 1 until day 7 and 14 as compared with the baseline in group NP. IT NSC transplantation significantly increased MWT and TWL and expression of BDNF in spinal dorsal horn and DRG in a dese-dependent manner at day 7 after operation in N1-5 groups as compared with group NP. There were no significant differences in MWT and TWL and BDNF expression among N3, N4 and N5 groups at day 21 after operation.Conclusion The proper quantity of transplanted NSCs which are able to ameliorate NP induced by partial transection of sciatic nerve in rats is 105 .

Objective:To investigate the clinical effect of lateral rectus abdominis approach combined with presacral decompression for surgical treatment of old Denis type II sacral fractures complicated with upper sacral plexus injury.Methods:A retrospective case series study was performed on the clinical data of 9 patients with old Denis type II sacral fractures complicated with upper sacral plexus injury (L 4-S 1) admitted to Zhongnan Hospital of Wuhan University from June 2010 to December 2016. There were 6 males and 3 females, aged (33.1±7.5)years (range, 15-58 years). Embolization of internal iliac artery and preimplantation of abdominal aortic balloon were performed 2 hours before operation under the guidance of digital subtraction angiography (DSA). Surgery was performed using a single lateral rectus abdominis approach combined with presacral decompression. The operation time, intraoperative blood loss and full weight-bearing time were recorded. The visual analogue scale (VAS) and European QOL Five Dimensional health scale (EQ-5D) were compared before and after operation. The Gibbons' impairment scale was used to assess neurological function. X-ray and CT scan were used to observe internal fixation and fracture healing. The complications during and after operation were recorded. Results:The patients were followed up for 24-52 months [(35.2±5.2)months]. The operation time was (2.9±0.6)hours. The intraoperative bleeding was (573±138)ml, and the full weight-bearing time was (11.6±1.2)weeks. X-ray and CT scan showed bone healing in all patients at the latest follow-up. The VAS and EQ-5D scale improved from preoperative (7.8±0.6)points and (0.34±0.07)points to the final follow-up of (0.8±0.3)points and (0.81±0.05)points ( P<0.05). According to Gibbons classification, 8 patients were grade I and 1 patient was grade II one year after operation ( P<0.01). Namely, the radiation pain of lower extremities was significantly improved in all patients, among which 8 patients showed pain disappeared and completely returned to normal and 1 patient showed residual numbness and hypoesthesia of the affected limbs. No major complications (eg, iatrogenic lumbosacral plexus injury, vital blood vessels or pelvic organs injury) occurred during the operation. During the follow-up period, only one patient developed traumatic hip arthritis and underwent total hip arthroplasty 6 months after operation. Fractures of the remaining patients were healed well without complications like infection, pressure ulcer or implant failure. Conclusions:For old Denis type II sacral fractures complicated with upper sacral plexus injury, lateral rectus abdominis approach combined with presacral decompression can fully decompress the upper sacral plexus nerve, relieve pain, and promote functional rehabilitation, with low incidence of complications. It is an alternative surgical method for the treatment of old Denis type II sacral fractures complicated with upper sacral plexus injury.

Purpose: Patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT). Materials and Methods: The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined. Results: Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)–positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016). Conclusion Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

Voltage-gated sodium (Na) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Na channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Na channels, with Na1.1 and Na1.5 each harboring more than 400 mutations. Na channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Na channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Ca) channel Ca1.1 provides a template for homology-based structural modeling of the evolutionarily related Na channels. In this Resource article, we summarized all the reported disease-related mutations in human Na channels, generated a homologous model of human Na1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Na channels, the analysis presented here serves as the base framework for mechanistic investigation of Na channelopathies and for potential structure-based drug discovery.
Animals ; Calcium Channels, L-Type ; chemistry ; genetics ; metabolism ; Channelopathies ; genetics ; metabolism ; Humans ; Mutation ; NAV1.1 Voltage-Gated Sodium Channel ; chemistry ; genetics ; metabolism ; NAV1.5 Voltage-Gated Sodium Channel ; chemistry ; genetics ; metabolism ; NAV1.7 Voltage-Gated Sodium Channel ; chemistry ; genetics ; metabolism ; Protein Domains ; Rabbits ; Structure-Activity Relationship

Adoptive cell therapy (ACT) is an emerging powerful cancer immunotherapy, which includes a complex process of genetic modification, stimulation and expansion. During these

Equilibrative nucleoside transporters (ENTs), which facilitate cross-membrane transport of nucleosides and nucleoside-derived drugs, play an important role in the salvage pathways of nucleotide synthesis, cancer chemotherapy, and treatment for virus infections. Functional characterization of ENTs at the molecular level remains technically challenging and hence scant. In this study, we report successful purification and biochemical characterization of human equilibrative nucleoside transporter 1 (hENT1) in vitro. The HEK293F-derived, recombinant hENT1 is homogenous and functionally active in proteoliposome-based counter flow assays. hENT1 transports the substrate adenosine with a K of 215 ± 34 µmol/L and a V of 578 ± 23.4 nmol mg min. Adenosine uptake by hENT1 is competitively inhibited by nitrobenzylmercaptopurine ribonucleoside (NBMPR), nucleosides, deoxynucleosides, and nucleoside-derived anti-cancer and anti-viral drugs. Binding of hENT1 to adenosine, deoxyadenosine, and adenine by isothermal titration calorimetry is in general agreement with results of the competitive inhibition assays. These results validate hENT1 as a bona fide target for potential drug target and serve as a useful basis for future biophysical and structural studies.
Adenine Nucleotides ; chemistry ; metabolism ; Equilibrative Nucleoside Transporter 1 ; chemistry ; genetics ; metabolism ; HEK293 Cells ; Humans ; Protein Domains ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; Structure-Activity Relationship