ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L^-1）， Coptidis Rhizoma group（B group， 38.4 g·L^-1）， processed Euodiae Fructus group（C group， 5.88 g·L^-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L^-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC_0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（C_max） of Ber， Pal， Evo， and Rut were the highest and time to peak（t_max） were the lowest in the liver of A group. In plasma， the AUC_0-t and C_max of Evo and Rut were increased in A group compared with C group， t_max of Pea was elevated and its C_max was decreased in A group compared with D group. In the liver， compared with B-D groups， C_max values of 5 representative components except Pae were elevated， AUC_0-t of Pae was decreased and AUC_0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t_1/2） of each representative components in A group was elevated and t_max was decreased， and C_max of each representative ingredient except Pal was decreased， AUC_0-t values of Ber and Pal were increased， whereas the AUC_0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

Social behavior is extremely important for the physical and mental health of individuals, their growth and development, and for social development. Social behavioral disorders have become a typical clinical representation of a variety of psychiatric disorders and have serious adverse effects on the development of individuals. The prefrontal cortex, as one of the key areas responsible for social behavior, involves in many advanced brain functions such as social behavior, emotion, and decision-making. The neural activity of prefrontal cortex has a major impact on the performance of social behavior. Numerous studies demonstrate that neurons and glial cells can regulate certain social behaviors by themselves or the interaction which we called neural microcircuits; and the collaboration with other brain regions also regulates different types of social behaviors. The prefrontal cortex (PFC)-thalamus projections mainly influence social dominance and social preference; the PFC-amygdala projections play a key role in fear behavior, emotional behavior, social exploration, and social identification; and the PFC-nucleus accumbens projections mainly involve social preference, social memory, social cognition, and spatial-social associative learning. Based on the above neural mechanism, many studies have focused on applying the non-invasive neurostimulation to social deficit-related symptoms, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES) and focused ultrasound stimulation (FUS). Our previous study also investigated that repetitive transcranial magnetic stimulation can improve the social behavior of mice and low-intensity focused ultrasound ameliorated the social avoidance behavior of mice by enhancing neuronal activity in the prefrontal cortex. In this review, we summarize the relationship between neurons, glial cells, brain projection and social behavior in the prefrontal cortex, and systematically show the role of the prefrontal cortex in the regulation of social behavior. We hope our summarization will provide a reference for the neural mechanism and effective treatment of social disorders.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To establish a rapid and convenient UPLC-MS/MS method for the determination of tamoxifen and its active metabolite endoxifen in plasma of patients with breast cancer.Methods With diazepam as the internal standard,the plasma sample was precipitated with acetonitrile and methanol-acetonitrile was used as mobile phase.The samples were separated by chromatographic column ZORBAX Eclipse plus C18(18 μm,2.1 mm x50 mm)and scanned by electrospray ion source and positive ion multiple reaction monitoring mode.The ion channels were detected as tamoxifen m/z 372.0→72.1,endoxifen m/z 374.0→58.2 and diazepam m/z 285→192.9.Results The linearity of tamoxifen and endoxifen were good in the concentration range of 1-500 ng·mL-1(R2=0.999 5)and 0.5-250 ng·mL-1,respectively(R2=0.999 9).The intra-day and inter-day precision of low,medium and high quality control concentrations were all less than 10％.Tamoxifen and endoxifen were stable at low temperature and stable after repeated freeze-thaw.Conclusion The experimental results show that the method meets the requirements of biological sample analysis,and the sample treatment is simple,specific,and can be used for the accurate and rapid determination of tamoxifen and indoloxifen in human plasma.

Conducting local tolerance testing on parentaral drugs is of great significance for evaluating the clinical medication risks of drugs.Although relevant domestic and international guidelines provide detailed instructions on how to conduct local tolerance testing,it was found that some products still provide non-standard application materials,which affects the efficiency of drug development.This article summarizes the information on domestic and international guidance related to the local tolerance testing and elaborates on common problems based on specific application cases,with the aim of of providing reference for related work.

Objective To explore the clinical efficacies of different surgical methods for elderly patients with lumbar tuberculosis.Methods The clinical data of 289 elderly patients with lumbar tuberculosis admitted to Hebei Chest Hospital from August 2018 to August 2021 were retrospectively analyzed.According to surgical methods,the patients were divided into the posterior group(109 cases),the anterior and posterior combination group(81 cases),and the anterior group(99 cases).The time of bone graft and fusion,operation time,hospital stay,intraoperative blood loss,and complications of the three groups were collected and compared among the three groups.The spine Cobb angle was regularly determined,the correction degree was calculated;the levels of erythrocyte sedimentation rate(ESR),white blood cell count(WBC),and C-reactive protein(CRP)were collected and compared among the three groups;and the Frankel grading and visual analogue scale(VAS)scores of the three groups were compared.Results After a 2-year follow-up,there was no significant difference in the time of bone graft and fusion among the three groups(P>0.05),the anterior group had the shortest operation time,the posterior group had the shortest hospital stay,and the lowest intraoperative blood loss and incidence of complications,with statistically significant differences(P<0.05).The correction degree of the anterior and posterior combination group was better than that of the posterior group and the anterior group(P<0.05),and the Cobb angles after operation and at the last follow-up in the posterior group was better(P<0.05).The anterior and posterior combination group had better improvement effect on CRP and ESR at the last follow-up(P<0.05),the WBC level of the posterior group was lower(P<0.05).The proportions of patients in grade E of Frankel grading at the last follow-up in the three groups were higher than those after surgery(P<0.05);compared with the preoperative period,the VAS scores at the last follow-up of the three groups decreased(P<0.05),and the VAS score of the posterior group was lower(P<0.05).Conclusion The effects of anterior surgery,posterior surgery and anterior and posterior combined surgery in the treatment of elderly lumbar tuberculosis are good,and the approach method can be scientifically and reasonably formulated according to patients' physical condition to improve the clinical treatment effect.

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

Objective:To investigate the safety,efficacy,and prognosis of high-dose melphalan in combination with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of multiple myeloma (MM). Methods:The clinical data of 17 patients with newly diagnosed MM who underwent ASCT as first-line consolidation therapy at the Yijishan Hospital of Wannan Medical College from March 2020 to October 2022 were retrospectively analyzed. The safety,efficacy,and prognosis of this treatment approach were evaluated. Results:Of the 17 patients,10 were male and 7 were female,with a median age of 56 (45-64) years. The stem cell engraftment rate was 100％,with a median neutrophil engraftment time of+10 (9-12) days and a median platelet engraftment time of+12 (10-21) days. The incidence of oral mucositis and intestinal infection after transplantation was 100％,with 2 cases of pulmonary infection,1 case of urinary tract infection,1 case of skin infection,and 11 cases of transient elevation of serum amylase. After transplantation,13 patients achieved a complete response (CR) or better,and the CR rate showed an increasing trend compared to before transplantation (13/17 vs 8/17;P=0.078). The median follow-up time was 18 (6-36) months,and 15 patients survived without progression,1 patient experienced disease progression,and 1 patient died due to clinical relapse and abandonment of treatment. The 2-year overall survival (OS) rate and progression-free survival (PFS) rate were approximately 90.0％ and 83.9％,respectively. Conclusion:High-dose melphalan in combination with ASCT as first-line consolidation therapy for MM can enhance the depth of patient response,further improve therapeutic efficacy,and the transplant-related complications are controllable,making it a viable option worth promoting in clinical practice.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective To understand the characteristics and developmental differences between cerebral organoids in vitro and normal cerebral cortices in vivo. Methods 1. Grouping: cerebral cortices in vivo group and cultured cerebral organoids in vitro group. 2. Sample collection: cortical tissues were collected from Kunming mouse embryos at embryonic day 7.5(E7.5), E9.5, E11.5, E14.5, and postnatal day 3 (P3) or P7. Three specimens were taken from each group. Meanwhile, cerebral organoids were cultured with mouse induced pluripotent stem cells (iPSCs), and samples at different culture time point were collected, and more than 3 samples were collected at each time point. 3. Detection method: the distribution of different types of cells in each group of specimens was analyzed by immunofluorescent staining. Results While relative similarities between in vivo cerebral cortical development and the cerebral organoids in vitro were observed, including the histogenesis, and the morphological differentiation of nerve cells and glial cells, the lamellar architecture of cerebral cortex in mouse brain was not observed in cerebral organoids. Conclusion The development of cerebral organoids in vitro has some similarity with body's cortical development. Therefore, cerebral organoids can be used to a substitution of cortex and diseases' models, but improvement of the existing technologies is necessary.