The training of clinical pharmacists in pain specialists often focuses on the education of professional knowledge,while neglecting the important role of ethics in the teaching process.Ethical elements such as the patient's right to informed consent,privacy,health,autonomy have not received sufficient attention in the teaching process.This training model poses a potential threat to patients'rights and interests and may bring ethical risks to pharmacists.To improve teaching quality and avoid risks,lecturers and trainees should deeply understand and respect the various rights of patients,safeguard their right to health from infringement,and ensure that privacy is fully protected.In addition,the patient's right to informed consent should be implemented to allow them to make autonomous choices based on a full understanding of the treatment plan,and humanistic care should be strengthened so that patients can feel the warmth and care from the pharmacists.Through the implementation of ethical measures,the paper aims to provide useful inspirations and references for the teaching work of clinical pharmacists in pain specialists,thereby promoting clinical pharmacists to achieve comprehensive improvement in professional skills and ethical literacy,and better serving the majority of pain patients.

Objective To investigate the effect of 5-Aza-CdR on Notch1 pathway and neural regeneration and to explore the effects of 5-Aza-CdR on learning memory ability in mice by exploring active avoidance behavior.Methods Sixty 6～8-week-old SPF-grade ICR male mice were divided into two groups.5-Aza-CdR was administered to one group of mice via lateral ventricular injection,while the control group was injected with bovine serum albumin.Notch1 and HES1 mRNA and protein expression levels were detected by Real-time PCR and Western blot 24 hours after injection;5-bromo-2'-deoxyuridine-positive cells were observed by laser confocal microscopy,and Notch1 expression in hippocampal dentate gyrus was viewed with laser confocal microscopy.Notch1 methylation changes were detected by ethylation-specific PCR,and learning and memory behaviors of mice were assessed by passive avoidance tests and shuttle avoidance assays.Results Injection of 5-Aza-CdR increased hippocampal Notch1 pathway activity,promoted neuronal regeneration in the DG region,decreased methylation levels in the Notch1 promoter region,and enhanced the ability of mice to perform active avoidance behavior.Conclusions The effect of 5-Aza-CdR on active avoidance behavior may be related to the influence of hippocampal neural regeneration through the Notch 1 pathway.

Objective:To analyze the whole genome sequence and key site mutations of hepatitis B virus (HBV) in patients with different stages of disease progression, and to understand the relationship between HBV genetic characteristics and disease progression.Methods:Serum samples and basic information of hepatitis B patients with asymptomatic HBV carrier, chronic hepatitis B patients, cirrhosis patients and primary hepatocellular carcinoma patients were collected. Nested PCR was used to amplify the samples to obtain HBV whole gene sequences. Phylogenetic trees were constructed to determine the genotype of the samples, and gene mutations of the samples were analyzed combined with reference sequences of each type.Results:A total of 256 samples were successfully amplified, including 68 asymptomatic HBV carrier patients, 118 CHB patients, 15 LC patients and 55 HCC patients, and five genotypes (B, C, D, I and C/D) were detected. The result of comparative analysis showed that the mutation rate of 56 nucleotide sites was significantly different among the four groups ( P<0.05). In addition to the discovery of C105T, A1762T/G1764A and G1899A and other previously reported key site mutations, the mutation rates of T53A, C1485T and C1628T in newly diagnosed HCC group were significantly higher than those in other groups, and the mutation rates of T2150G and T2151C in asymptomatic HBV infection group were significantly higher than those in other groups. A total of 26 sequences were deleted, mainly distributed in the pre-C and pre-S regions. The deletion mutation rate in the HCC group was significantly higher than that in the other groups. Conclusions:The data of this study indicate that some nucleotide substitution mutations and deletion mutations may be closely related to the occurrence and development of HBV-related diseases, and HCC patients are more likely to have gene mutations than non-HCC patients. These result provide a reference for understanding the relationship between viral mutation and the progression of HBV infection-related diseases.

OBJECTIVE: To identify the protective effect of empagliflozin on ischemic brain injury and neurological dysfunction in mice, and further explore its potential mechanism. METHODS: Acute cerebral ischemia model was induced by the permanent middle cerebral artery occlusion surgery in C57BL/6J mice. Empagliflozin(10 and 30 mg·kg−1) was administered to mice one hour after the onset of occlusion. Brain infarct volume and neurological defect score were assayed 24 h after surgery. Mice were subjected to photo-thrombosis and further administered with empagliflozin 3, 10, 30 mg·kg−1 intragastricly for either 7 or 14 consecutive days. The grid-walking task and the cylinder task were performed daily to determine the sensory-motor function of the mice. Alternatively, the mice were treated with 10 mg·kg−1 empagliflozin simultaneously with 10% glucose(i.p.) for 7 consecutive days after the photo-thrombosis model to evaluate their motor sensory function. Immunofluorescence staining was used to detect the activation of microglia within the infarct area 7 d after the photo-thrombosis. RESULTS: One hour after permanent middle cerebral artery occlusion surgery, gavage of empagliflozin significantly increased the brain infarct volume and neurological dysfunction. While in photo-thrombosis surgery, treatment of empagliflozin(10 mg·kg−1) for consecutive 7 or 14 days significantly decreased the rate of false foot in grid-walking task and the assymetric index in cylinder task. At the dose of 30 mg·kg−1, however, empagliflozin even aggravated photo-thrombosis-induced neurological dysfunction, while the dose of 3 mg·kg−1 showed no effect. Unexpectedly, the protective effect of empagliflozin(10 mg·kg−1) could not be reversed by glucose treatment. The results of immunofluorescence showed that empagliflozin(10 mg·kg−1) significantly alleviated the microglia activation in the ischemic area after the photo-thrombosis operation. CONCLUSION Empagliflozin cannot protect against acute ischemia-induced brain injury in mice. Empagliflozin alleviated ischemia-induced neurological dysfunction with consecutive administration in a dose-related manner. Empagliflozin-conferred neuroprotection may not be attributable to its effects on lowing blood glucose. Alternatively, empagliflozin may play a neuroprotective effect by inhibiting the excessive activation of microglia in ischemic brains.

Objective:To explore the value of contrast enhancement T1 fluid-attenuated inversion recovery sequence (CE-T1FLAIR) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in detecting metastases.Methods:One hundred and seventy-six patients with pathologically diagnosed malignant tumors and brain metastases accepted enhanced 3.0T MRI scan in Department of Medical Imaging, He'nan Provincial Cancer Hospital from October 2023 to February 2024 were enrolled. Lianying's intelligent brain metastasis AI-assisted detection system and sequences of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR were used to detect the brain metastasis lesions, respectively. Length of the lesions was measured according to Lianying's intelligent brain metastasis AI-assisted detection system, and all lesions were divided into 3 categories: <3 mm, 3-10 mm, and >10 mm. Differences in detection rate in brain metastases of different lengths and locations among the 3 sequences were compared.Results:Detection rates of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR, and FSE CE-T1FLAIR in brain metastases were 99.67%, 90.52%, and 71.02%, which were decreased successively, with significant differences ( P<0.05). Detection rates of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR in brain metastases with length<3 mm (99.24%, 79.95% and 46.45%) or length of 3-10 mm (100%, 98.19% and 87.53%) were decreased successively, with significant differences ( P<0.05). Detection rates of MATRIX CE-T1FLAIR (100%, 80.56% and 64.24%), 3D GRE_fsp CE-T1FLAIR (100%, 97.25% and 76.11%), and FSE CE-T1FLAIR (100%, 91.18% and 70.59%) in metastases at the superficial area of the brain convexity, gray-white matter junction area, and cerebellum were decreased successively, with significant differences ( P<0.05). Detection rates of FSE CE-T1FLAIR in brain metastases in the basal ganglia and brainstem (69.33% and 50%) were significantly lower than those of MATRIX CE-T1FLAIR and 3D GRE_fsp CE-T1FLAIR (97.33% and 92.86%; 88% and 78.57%, P<0.05). Conclusion:MATRIX CE-T1FLAIR sequence is better than 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR sequences in detecting brain metastases, especially for metastases with length<10 mm and metastases located at the superficial area of the brain convexity, gray-white matter junction area and cerebellum.

Objective To construct a prognostic model for uterine corpus endometrial carcinoma(UCEC)using the prognosis-associated ADME genes involved in controlling drug absorption,distribution,metabolism,and excretion(ADME),providing a reference for predicting the prognosis of UCEC and tumor treatment.Methods The gene expression and clinical information data of UCEC were obtained from the TCGA and ICGC databases.Prognosis-related ADME genes were screened using the univariate Cox regression analysis.Least absolute shrinkage and selection operator(LASSO)regression was used to identify optimal prognostic genes,and then a risk score model was constructed.Kaplan-Meier curve and receiver operating characteristic(ROC)curve were constructed to assess predictive capability.R software was used to perform differentially expressed genes anal-ysis,functional enrichment analysis.Results A nine-gene signature(DHRS7B,CYP46A1,SLCO4C1,NR1I2,SLC16A1,SLCO3A1,ARSA,ABCC5,MGST2)was used for constructing a risk score model.Survival analysis showed that the survival time in high-risk patients was significantly shorter than in low-risk patients(the train set:P＜0.001;the test set:P=0.032).The are-as under the ROC curve of the train set and the test set for ROC at 1,3,5 years were 0.792,0.724,0.712,and 0.651,0.620,0.677,respectively.Univariate and multivariate Cox regression analysis showed that the risk score was an independent risk factor for UCEC(HR=1.77,P=0.035).In addition,there was a significant difference in the miRNA-mediated silencing and regulation of sprouting angiogenesis pathways between the high-risk and low-risk score groups.Conclusion The prognosis model con-structed with nine key ADME genes may have the potential to be used for predicting the survival prognosis of patients with UCEC.

Objective This study systematically evaluated the clinical efficacy of Shangke Jiegu tablet in the treatment of fracture,and explored the mechanism of action of Shangke Jiegu tablet and the compatibility of each efficacy group from the"Disease-Symptom-Formula"perspective.Methods Clinical research literatures on the use of Shangke Jiegu tablet for fracture intervention were retrieved from Chinese databases(CNKI,Wanfang Database,VIP database)and English databases(PubMed,Cochrane Library,EMbase),covering the period from the inception of the databases to January 2024.Risk assessment tools were used to evaluate the literature's quality,and the data were extracted and analyzed using Stata 16.0 software.Gene sets associated with fracture symptoms were identified through the TCMIP platform(version 2.0).Differential gene expression related to fractures was obtained from the GEO database.Chemical composition and candidate target profiles of the 12 herbs in Shangke Jiegu tablets were collected from TCMIP v 2.0.An interaction network between fracture-related genes and drug candidate targets was established,and core network targets were screened based on topological features,with functional enrichment analysis performed.Results A total of 14 articles were incorporated into the Meta-analysis,encompassing a total sample size of 1 293 cases,indicating an overall response rate of Shangke Jiegu tablets in fracture therapy(RR=1.24,95%CI:1.18-1.31,P<0.001).The"Disease-Symptom-Formula"association network analysis indicated that the pathways related to the putative targets of Shangke Jiegu tablet were primarily involved in bone healing,nerve and blood system regulation,and immune-inflammation regulation.Different efficacy groups within the prescriptions showed varying emphases on these roles.Conclusions Shangke Jiegu tablet may facilitate fracture healing by regulating blood and nervous systems,correcting immune-inflammatory imbalances,and maintaining bone and energy metabolism.The comprehensive effects include the dissipation of blood stasis,the promotion of blood circulation,the alleviation of swelling and pain,the regeneration of muscles and bones,and the clearance of heat and detoxification.These findings support the clinical advantages and positioning of Shangke Jiegu tablet.

Objective To investigate the value of prediction of the differentiation level in lung adenocarcinoma based on CT radiomics model.Methods Data from 507 patients with postoperative pathological confirmed lung adenocarcinoma and clearly defined differentiation level of lung adenocarcinoma were retrospective analyzed.The enrolled cases were divided into poorly differentiation group and moderate-to-high differentiation group based on the grading criteria.CT image features were extracted,and seven machine learning algorithms were used to construct prediction models to obtain the AUC,accuracy,specificity,and sensitivity.Results The poorly differentiation group consisted of 175 cases,while the moderate-to-high differentiation group had 332 cases.The XGBoost model demonstrated the best performance,with the AUC,accuracy,specificity,and sensitivity of this model on the validation set being 0.878,0.829,0.667,and 0.727,respectively.Conclusion CT radiomics model can effectively predict the differentiation level of poorly differentiation and moderate-to-high differentiation in lung adenocarcinoma.

ObjectiveTo elucidate the mechanism of Osteoking against fracture， femoral head necrosis， osteoarthritis， and lumbar disc herniation by integrating heterogeneous information network mining and experimental validation. MethodOn the basis of the disease-related database and transcriptome expression profiling dataset， as well as the ETCM database， the gene sets related to four target diseases and the candidate target spectrum of Osteoking were obtained through the integration and analysis of bioinformatics data， and a "disease-syndrome-formula-target-pathway-effect" heterogeneous information network was constructed. In addition， by functional enrichment analysis， the core targets of Osteoking in interfering with the imbalance network of four kinds of bone injury diseases， the biological pathways involved， and the corresponding clinical symptoms were screened， and they were verified in animal experiments. ResultHeterogeneous information network mining indicates that Osteoking may commonly reverse the imbalance networks of fracture， femoral head necrosis， osteoarthritis， and lumbar disc herniation via regulating cell function and activity， inhibiting inflammatory response， reducing bone destruction， and improving the immune function of the body by modulating relevant core candidate targets such as RAC-alpha serine/threonine-protein kinase （Akt1）， catenin beta-1 （CTNNB1）， epidermal growth factor receptor （EGFR）， heat shock protein 90-alpha （HSP90AA1）， and phosphatidylinositol 3-kinase catalytic subunit alpha isoform （PI3KCA）， as well as related biological pathways such as phosphatidylinositide 3-kinases/protein kinase B （PI3K/Akt）， janus kinase/signal transducer and activator of transcription （JAK/STAT）， tumor necrosis factor （TNF）， nuclear factor kappa-B （NF-κB）， and Toll-like receptors. In particular， Osteoking may improve the blood supply of the fracture end by regulating blood circulation at the target site of the disease， and it may maintain the balance of bone metabolism by regulating hormone-related pathways to promote fracture healing. In addition， Osteoking may relieve lipid metabolism disorders by targeting and regulating lipid-related pathways， accelerate bone formation and bone repair， and delay the progression of femoral head necrosis. Osteoking may relieve the symptoms of pain by acting on neurological pathways to reduce local nociceptive stimulation in patients with osteoarthritis and lumbar disc herniation. Further experimental validation demonstrates that the PI3K/Akt signaling pathway is the most significantly enriched pathway for the key network targets of Osteoking for the four diseases. The candidate target of Osteoking may have the strongest association with the network of fracture-related genes. Therefore， this study chooses fracture as the target disease to verify the efficacy of Osteoking. The results show that Osteoking can accelerate bone formation and promote fracture healing by inhibiting the activation of the PI3K/Akt signaling axis. ConclusionThe study shows that the main mechanism of "treating different diseases with an identical treatment" of four bone injury diseases with Osteoking involves cell function regulation and immune inflammation-related signaling pathways. Further experimental validation identifies that the PI3K/Akt signaling axis may be one of the key pathways of Osteoking to promote bone regeneration， bone reconstruction， and bone metabolism homeostasis.

ObjectiveFrom the perspective of energy metabolism， the mechanism of Osteoking （OK） in the treatment of myofascial pain syndrome （MPS） was revealed through systems biology prediction combined with holistic animal experimental validation methods. MethodFirstly， the key targets of MPS and their related molecular mechanisms were predicted by the systems biology method， and the core network targets were screened. Then， the network-predicted targets were verified by animal experiments. Specifically， 60 SD rats were randomly divided into normal group， model group， low， medium， and high dose OK groups （0.66， 1.31， 2.63 mL·kg^-1）， and positive celecoxib group （21 mg·kg^-1）. The MPS model was established by beating combined with a centrifugal exercise method for eight weeks. Except for two days after modeling， the intervention of OK or celecoxib was performed. After the completion of the model， the drug was administered for two weeks. The histopathological changes of trigger point muscle tissue were observed by hematoxylin-eosin staining. The content/activity of Na-K-ATP enzyme （Na⁺-K⁺-ATPase）， Ca²⁺ pump （Ca²⁺ATPase）， Ca²⁺， lactate dehydrogenase （LDH）， glutathione （GSH）， malondialal （MDA）， superoxide dismutase （SOD）， cyclic adenosine phosphate （cAMP）， and protein kinase A （PKA） in serum and/or trigger point muscle tissue in MPS rats was detected by enzyme-linked immunosorbent assay. Protein expression levels of PKA and the peroxisome proliferator-activated receptor γ coactivator 1α （PGC1α） in MPS rats were detected by immunohistochemistry. The protein expression levels of PKA， PGC1α， and mitochondrial transcription factor A （TFAM） in MPS rats were detected by Western blot. ResultThe network prediction results suggest that OK acts on the key target of energy metabolism related to the occurrence and development of MPS and may participate in the activation of the cAMP/PKA/PGC1α signaling pathway. The experimental validation results show that compared with the normal group， contracture nodules and disordered arrangement of muscle fibers appear in the trigger point muscle tissue of MPS rats. Na⁺-K⁺-ATPase， Ca²⁺ATPase， SOD activity， Ca²⁺， and GSH contents in serum and/or trigger point muscle tissue are significantly decreased （P<0.01）. Both LDH activity and MDA contents are significantly increased （P<0.01）， and the protein expression levels of cAMP， PKA， PGC1α， and TFAM are significantly decreased （P<0.01）. Compared with the model group， OK improves the histopathological morphology of trigger point muscle fibers in MPS rats， and after the intervention of OK， Na⁺-K⁺-ATPase， Ca²⁺ATPase， SOD activity， Ca²⁺， and GSH contents in serum and/or trigger point muscle tissue in MPS rats are significantly increased （P<0.05， P<0.01）. LDH activity and MDA contents are significantly reduced （P<0.05， P<0.01）. The protein expression levels of cAMP， PKA， PGC1α， and TFAM are significantly increased （P<0.05， P<0.01）. ConclusionThe mechanism of OK's intervention in MPS rats may be related to its effective activation of the cAMP/PKA/PGC1α signaling pathway， thus promoting mitochondrial energy metabolism and trigger point muscle fiber damage repair in muscle cells.