OBJECTIVE To explore the potential mechanism of ketamine-induced cognitive impairment in mice based on metabolomics. METHODS Male C57BL/6 mice were randomly divided into control group and ketamine group （25 mg/kg）， with 12 mice in each group. Each group of mice was intraperitoneally injected with normal saline or corresponding drugs， 4 times a day， for 10 consecutive days. On the last 2 days of drug administration， the cognitive behavior was evaluated by Y maze and novel object recognition test， and the histopathological changes in the prefrontal cortex （PFC） were observed. Ultra-high performance liquid chromatography-tandem mass spectrometry technology was used to analyze the changes of metabolites in PFC， screen for differential metabolites， and perform pathway enrichment analysis. RESULTS Compared with the control group， the morphology of PFC neurons in the ketamine group of mice was inconsistent. There were cavities around the nucleus， and the number of deeply stained cells increased. The mean optical density value of the Nissl staining positive area was significantly reduced， and the alternation rate and discrimination index were significantly reduced （P＜0.05 or P＜0.01）. In the PFC tissue samples of mice of the two groups， there were a total of 114 differential metabolites， including 73 up-regulated and 41 down-regulated metabolites， including glutamine， succinic acid， ketoglutarate， and choline， etc. The differential metabolites mentioned above were mainly enriched in metabolism of alanine， aspartate and glutamate， metabolism of arginine and proline， γ aminobutyric acid synapses， pyrimidine metabolism， cholinergic synapses pathways， etc. CONCLUSIONS Ketamine can induce cognitive impairment in mice. Its neurotoxicity is related to abnormal synaptic transmission and energy metabolism， and neuroimmune regulation disorders.

Objective To observe the effects of Yiqi Huoxue Tuodu Prescription on Keap1Nrf2/HO-1 signaling pathway in rats with chronic nonbacterial prostatitis(CNP);To explore its mechanism for the treatment of CNP.Methods CNP rat model was prepared using castration combined with estrogen induction method.Totally 48 SD rats were divided into blank group,model group,celecoxib group and Yiqi Huoxue Tuodu Prescription group according to the random number table method,with 12 rats in each group.In the celecoxib group,celecoxib suspension was instilled 0.035 g/kg,and in the Yiqi Huoxue Tuodu Prescription group,Yiqi Huoxue Tuodu Prescription water decoction was instilled 8.64 g/kg,and the blank group and the model group were instilled with equal volume of normal saline for 28 days.Mechanical pain threshold in rats was measured using Von Frey fiber optic pain gauge,HE staining was used to observe pathological changes in prostate tissue and pathological scoring,the content of reactive oxygen species(ROS)in prostate tissue were detected by chemical fluorescence method and the glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)content in prostate tissue were detected by colorimetric method,Western blot was used to detect the expressions of Kelch like ECH related protein 1(Keap1),nuclear factor E2 related factor 2(Nrf2),and heme oxygenase-1(HO-1)protein in prostate tissue.Results Compared with the blank group,rats in the model group had significantly lower mechanical pain threshold and significantly decreased prostate index(P<0.01);the size of the glandular cavity in prostate tissue varied,with the disappearance of secretions in the cavity,interstitial looseness and edema,a large amount of fibrous tissue hyperplasia and inflammatory cell infiltration,and a significant increase in pathological scores(P<0.01);the contents of ROS and MDA in prostate tissue significantly increased,the activity of GSH-Px significantly decreased(P<0.01),the expression of Keap1 and Nrf2 proteins significantly decreased,and the expression of HO-1 protein significantly increased(P<0.01,P<0.05).Compared with the model group,the mechanical pain threshold of the rats in the Yiqi Huoxue Tuodu Prescription group was significantly higher(P<0.01);there was mild damage to prostate tissue,with a small amount of fibrous hyperplasia and inflammatory cell infiltration,and a significant decrease in pathological scores(P<0.01,P<0.05);the contents of ROS and MDA in prostate tissue significantly decreased,and the GSH-Px activity significantly increased(P<0.01),the Keap1 and Nrf2 protein expressions significantly increased and HO-1 protein expression significantly decreased in prostate tissue(P<0.01,P<0.05).Conclusion Yiqi Huoxue Tuodu Prescription can effectively improve the histopathological morphology and increase the pain threshold of the prostate gland in CNP rats,and its mechanism of action may be related to the regulation of Keap1/Nrf2/HO-1 signaling pathway and reduction of oxidative stress damage in prostate tissue of rats.

Oral and maxillofacial malignant tumors threaten the life and health of patients, and seriously affect their swallowing, language function and face. 125I seeds brachytherapy for oral and maxillofacial malignant tumors has been widely concerned and studied because of its advantages such as less surgical trauma, large and uniform dose distribution in the target tissue, little damage to the surrounding normal tissue, and reducing radiation exposure of medical staff. Low-dose brachytherapy with 125I seeds can effectively reduce the tumor volume and prolong the survival time of patients. This article reviews the clinical application of 125I seeds brachytherapy in oral and maxillofacial malignant tumors.

Objective:Trigeminal neuralgia(TN)is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy.There are numerous treatments for TN,but currently the main clinical approach is to suppress pain by carbamazepine(CBZ).Brain-derived neurotrophic factor(BDNF)is closely related to chronic pain.This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion(TG)and serum of TN via a chronic constriction injury of the infraorbital nerve(ION-CCI)rat model. Methods:The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group,a TN group,a TN+low-dose CBZ treatment group(TN+20 mg/kg CBZ group),a TN+medium-dose CBZ treatment group(TN+40 mg/kg CBZ group),and a TN+high-dose CBZ treatment group(TN+80 mg/kg CBZ group).The mechanical pain threshold in each group of rats was measured regularly before and after surgery.The expressions of BDNF and tyrosine kinase receptor B(TrkB)mRNA in TGs of rats in different groups were determined by real-time PCR,and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence.Western Blotting was used to detect the protein expression of BDNF,TrkB,extracellular regulated protein kinases(ERK),and phospho-extracellular regulated protein kinases(p-ERK)in TGs of rats in different groups.The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay(ELISA). Results:The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery(all P>0.05).From the 3rd day after operation,the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group(all P<0.01),and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 CBZ mg/kg group was higher than that in the TN group(all P<0.05).The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group(all P<0.05),and those in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than the TN group(all P<0.05).The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group(all P<0.05).The BDNF and neuron-specific nuclear protein(NeuN)were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group(all P<0.05).The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group(P<0.05).The levels of BDNF in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold(r=-0.650,P<0.01). Conclusion:CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats,reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway,so as to inhibit TN.The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

Objective To explore the relevant relationship and specificity between the implicit and explicit loyalty of military cadets in order to provide a theoretical basis and objective indicators for a more comprehensive and objective assessment for individual loyalty.Methods E-Prime 2.0,a classic implicit association paradigm was employed to construct an implicit association loyalty test for 64 military cadets.Simultaneously,an explicit loyalty measurement was conducted using the Chinese Military Personnel Loyalty Scale.Results ① Significant implicit effect was observed in the loyalty assessment of military cadets,indicating a general tendency to perceive higher levels of personal loyalty and lower levels of loyalty to external entities.② Explicit loyalty assessment revealed that the participants had the highest loyalty score towards the Party,the Nation,and the People(4.79±0.34),followed by the loyalty score to their profession(4.38±0.53),and the relatively lower loyalty score towards the unit and leaders(4.03±0.83).Among the 3 dimensions of loyalty,the normative loyalty score ranked highest,while continuance loyalty score took lower.③ There were no correlations among the scores of loyalty to the Party,the Nation,and the People(r=-0.030,P=0.823),to the profession(r=-0.047,P=0.728),to the unit(r=0.050,P=0.710),or to the leaders(r=0.043,P=0.749).Conclusion The implicit effect in the loyalty assessment is significant in military cadets,and there is no significant correlation between explicit and implicit loyalty measurements.Thus,we cannot rely solely on explicit measurements to assess their loyalty attitudes.

Objectives:Present study analyzed the efficacy and safety of percutaneous coronary intervention(PCI)using the distal transradial access(dTRA)for patients with complex coronary lesions. Methods:A total of 10 033 patients with complex coronary artery lesions(type B2 and type C lesions)who underwent percutaneous coronary intervention(PCI)via dTRA or conventional transradial access(TRA)at Fuwai Hospital between June 2021 and May 2022 were included(9 625 patients in the TRA group and 408 patients in the dTRA group).After propensity score matching,391 patients were included in each group.Baseline data,PCI intraoperative data(including lesion characteristics,intervention success rate,etc.),and incidence of major bleeding related to the access were compared between the two groups before and after propensity score matching. Results:Before propensity score matching,the proportions of patients with hypertension,hyperlipidemia,family history of coronary heart disease,history of myocardial infarction,and history of coronary artery bypass grafting were significantly higher in the dTRA group than in the TRA group(all P<0.05).After propensity score matching,the baseline data of the two groups were similar(all P>0.05).Before propensity score matching,compared with the TRA group,patients in the dTRA group had a higher proportion of patients with type B2 lesions,while the proportions of patients with type C lesions and those using intravascular ultrasound(IVUS)were lower(all P<0.05).The proportion of patients with chronic complete occlusion was similar between the two groups(P>0.05).After propensity score matching,compared with the TRA group,patients in the dTRA group had a lower proportion using IVUS and had a higher percent of stent implantation(both P<0.05).There was no statistically significant difference between the two groups in terms of SYNTAX score,guide catheter size,target lesion distribution,proportion of patients using intra-aortic balloon counterpulsation,success rate of intervention procedures,and incidence of major bleeding events related to the access(all P>0.05). Conclusions:Compared with the conventional TRA,interventional treatment of complex lesions through dTRA is equally safe and effective for patients with complex coronary lesions.

Objective:To investigate the effectiveness and feasibility of whole exome sequencing (WES), as a molecular diagnosis technique, for adult patients with genetic diseases.Methods:The present retrospective analysis included 445 adult patients (ages 18-80 years) with suspected genetic diseases who underwent whole exome sequencing (WES) from August 2021 to December 2022. The pathogenicity classification of each variant was assessed in accordance with the recommendations developed by the American Society of Medical Genetics and Genomics.Results:The overall positive rate of WES among adult patients with suspected genetic diseases was 28.08% (125/445). The highest positive rate was observed in the age group of 41-50 years (34.33%, 23/67). Among the diagnosed genetic diseases, those affecting the cardiovascular system (63.16%, 84/133), nervous system (18.05%, 24/133), and endocrine system (13.53%, 18/133) ranked as the top three. The most common genetic diseases identified through WES in adult patients were hypertrophic cardiomyopathy (18.80%, 25/133), dilated cardiomyopathy (16.54%, 22/133), Marfan syndrome (15.04%, 20/133), epilepsy (9.02%, 12/133), and familial hypercholesterolemia (4.51%, 6/133). The main causative genes identified included FBN1 (14.29%, 19/133), MYBPC3 (9.02%, 12/133), MYH7 (9.02%, 12/133), LDLR (3.76%, 5/133), TTN (3.76%, 5/133), and TNNI3 (3.01%, 4/133).Conclusion:Applying the WES technique in clinical practice can improve the diagnostic rate of adult genetic diseases, especially in adult patients with suspected genetic conditions involving the cardiovascular system, nervous system, and endocrine system.

In recent years,the use of bioprosthetic mitral valves has been increasing,leading to a growing number of patients experiencing bioprosthesis degeneration,significantly impacting their quality of life.The high risk of reoperation has deprived many patients with mitral bioprosthesis degeneration of the opportunity for a second surgery.With the rapid development of interventional procedures in our country,transcatheter mitral valve-in-valve replacement is gradually being accepted by a large number of patients with bioprosthesis degeneration.We report a case of transcatheter mitral valve-in-valve replacement via transseptal puncture.The surgical plan was carefully formulated based on preoperative CT evaluation,and the patient underwent the procedure smoothly with no significant adverse events postoperatively.Transcatheter mitral valve-in-valve replacement may be a better alternative for patients at high risk of mitral bioprosthesis degeneration.

The pharmacy department of medical institutions assumes important responsibilities in the emergency response work.The standard of pharmacy administration in emergencies is formulated based on the principles of scientificity,versatility,instructiveness,and operability,through sorting out problems,collecting opinions and expert argumentation.This standard has 49 standards of 9 key elements from three aspects:emergency mechanism,emergency support,and emergency services.This article aims to introduce the construction method and formulation process of the pharmacy administration in emergency standards,and analyzes the content,to guide for improving emergency response ability of the medical institutions'pharmacy department in emergency events.

The pathogenesis of the nephrotic syndrome is complex and the pathological types are diverse, so the minor symptoms in its early phases are difficult to detect. Renal biopsy is the gold indicator for the diagnosis of renal pathology and progression, but poor patient compliance shows, and the optimal treatment time is often delayed. Therefore, the discovery of biomarkers for early diagnosis and disease progression monitoring is of great clinical significance. In this study, doxorubicin-injured podocyte models were used to simulate human kidney disease at different stages of progression. LC-MS-based metabolomic technology combined with statistical methods was used to screen and identify the potential biomarkers associated with early injury or progression of podocytes. The results of cell viability, apoptosis tests and podocyte structural protein analysis showed that the model was successfully constructed, and the degree of podocyte injury was significantly different between the two modeling methods. According to VIP > 1 and P < 0.05 based on the orthogonal partial least squares discriminant analysis (OPLS-DA) model, nine differential metabolites reflecting early podocyte injury and twelve differential metabolites reflecting the injury progression were screened, respectively. ROC analysis was adopted to focus on the potential biomarkers that can reflecting the early podocyte injury including L-tryptophan, guanosine triphosphate (GTP), 5′-thymidylic acid (dTMP) and thymidine, and the biomarkers reflecting the injury progression of podocytes composed of L-phenylalanine, L-tyrosine acid, uridine 5′-diphosphate (UDP) and guanosine 5′-diphosphate (GDP) AUC > 0.85. It indicated that these eight metabolites may have high sensitivity and diagnostic ability. This study provides a reference for the research on biomarkers of progressive diseases.