Major depressive disorder(MDD)is a prevalent con-dition associated with substantial impairment and low remission rates.Traditional antidepressants demonstrate delayed effects,low cure rate,and inadequate therapeutic effectiveness for man-aging treatment-resistant depression(TRD).Several studies have shown that ketamine,a non-selective N-methyl-D-aspartate receptor(NMDAR)antagonist,can produce rapid and sustained antidepressant effects.Ketamine has demonstrated efficacy for reducing suicidality in TRD patients.However,the pharmaco-logical mechanism for ketamine's antidepressant effects remains incompletely understood.Previous research suggests that the an-tidepressant effects of ketamine may involve the monoaminergic,glutamatergic and dopaminergic systems.This paper provides an overview of the pharmacological mechanism for ketamine's anti-depressant effects and discuss the potential directions for future research.

Objective To explore the efficacy of vaginal lesion resection combined with uterine wall repair in the treatment of cesarean scar pregnancy(CSP)after cesarean section.Methods A total of 122 patients with CSP admitted to our hospital were selected and randomly divided into the control group(61 cases)and the observation group(61 cases).Patients in the control group were treated with uterine artery chemoembolization(UACE)combined with ultrasound-guided curettage,while patients in the observation group were treated with vaginal lesion resection combined with uterine wall repair.The perioperative index,serum beta-human chorionic gonadotropin(β-hCG)levels before surgery and 3 days,5 days,and 7 days after surgery,clinical efficacy,and complications of patients between the groups were compared.Results The operation time of patients in the observation group was significantly longer than that in the control group(P<0.05),and the amount of intraoperative blood loss,hospitalization cost,vaginal bleeding time,time to menstruation recovery,mass disappearance time,β-hCG normalizing time,and hospitalization time of patients in the observation group were significantly less/shorter than those in the control group(P<0.05).The serum β-hCG levels of patients 3 days,5 days and 7 days after surgery in both groups were lower compared with those before surgery,and the observation group was lower than the control group,with statistically significant differences(P<0.05).The total effective rate in the observation group was 96.72%,significantly higher than that of 85.25%in the control group(P<0.05).The incidence of vaginal bleeding and surrounding tissue injury in the observation group was significantly lower than that in the control group(P<0.05).Conclusion The combination of vaginal lesion resection and uterine wall repair for the treatment of CSP can reduce the amount of intraoperative blood loss,reduce the serum β-hCG levels and the incidence of complications,improve clinical treatment efficacy,and promote recovery of patients.

Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.

Objective:Fatigue is one of the common disabling non-motor symptoms of multiple system atrophy(MSA).This study aimed to investigate the prevalence of fatigue in MSA patients and its relationship with anxiety and depression.Methods:In this cross-sectional study, 44 MSA inpatients from Xuanwu Hospital of Capital Medical University were enrolled.Fatigue was defined as a Fatigue Severity Scale(FSS)score ≥4.The motor symptoms of the patients were evaluated using the Unified Parkinson's Disease Rating Scale(MDS-UPDRS)and Unified Multi-System Atrophy Rating Scale(UMSARS).The Hamilton Rating Scale for Depression(HAMD), Geriatric Depression Scale(GDS)and Hamilton Anxiety Scale(HAMA)were used to assess anxiety and depression.Results:The mean age of the MSA patients was 60.1±6.4 years, and the score of FSS was 4.3±2.4, with 28 patients(63.6%)having fatigue.Compared with the non-fatigue group, the fatigue group showed clear anxiety(HAMA: 16.5±8.9 vs.9.4±5.0, t=-2.292, P=0.010)and depression(HAMD: 14.4±7.0 vs.8.4±3.4, t=6.192, P=0.017; GDS: 18.2±7.4 vs.10.7±5.2, t=-3.560, P=0.044).The severity of fatigue in MSA patients was positively correlated with anxiety( r=0.516, P<0.001), depression(HAMD: r=0.551, P<0.001; GDS: r=0.636, P=0.000)and the score of activities of daily living( r=0.320, P=0.034), but not correlated with motor symptoms or disease severity. Conclusions:Nearly two-thirds of MSA patients have symptoms of fatigue, and fatigue is significantly associated with levels of anxiety and depression, affecting patients' mood and activities of daily living.

Multiple system atrophy(MSA)is a rapidly progressive neurodegenerative disease and, along with Parkinson's disease(PD)and dementia with Lewy bodies(DLB), belongs to the group of α-synucleinopathies.Due to an overlap of clinical symptoms of similar diseases in the early stages and a lack of sensitivity of the current diagnostic criteria to detect the disease in the early stages, difficulties abound in conducting clinical trials on disease-modifying therapeutic agents for its early treatment, and progress in the development of disease-modifying therapeutic agents as well as the development and validation of diagnostic tools has been slow.Consequently, the International Movement Disorder Society(MDS)has introduced new diagnostic criteria for MSA, which, for the first time, propose a category known as possible prodromal MSA and its diagnostic criteria.This review described the diagnostic criteria for possible prodromal MSA and its differential diagnosis from other prodromal α-synucleinopathies, in order to improve the accuracy of diagnosis in the early stages and to promote research on the early stages of the disease.

Objective:To investigate the safety and clinical effect of testis-sparing microsurgery(TSMS)in the treatment of benign testis tumor(BTT).Methods:We retrospectively analyzed the clinical data on 16 cases of BTT treated in the Department of Andrology of the Affiliated Hospital of Qingdao University from October 2020 to February 2023.The median age of the patients was 23 years.All the tumors were unilateral,7 in the left and 9 in the right side,with a median diameter of 1.85 cm(1.0-3.5 cm).The patients all underwent color Doppler flow imaging(CDFI),MRI,semen analysis and examination of serum T,alpha-fetoprotein(AFP),human chorionic gonadotropin(HCG)and lactate dehydrogenase(LDH),followed by TSMS.The boundaries between the tumors and normal testis tissue were accurately identified under the microscope,and the tumors and the adjacent normal testis tissue 2 mm from their margins were excised completely.Bipolar coagulation forceps were used for wound hemostasis to maximally preserve the normal testis tissue.The resected specimens were subjected to fast frozen pathology intraoperatively,and the patients were followed up for 14-40 months by regular scrotal CDFI,MRI and examinations of serum T and semen parameters.Results:The levels of serum T,AFP,HCG and LDH and semen parameters were all within the normal range preoperatively.TSMS were successfully completed in all the cases,and all were pathologically confirmed as BTT according to the latest edition of WHO Classification of Tumors:Urinary and Male Genital Tumors.CDFI showed normal blood supply within the testis tissue at 1 month after surgery.No signs of intra-testicu-lar tumor residue,recurrence or metastasis,nor significant changes in the levels of serum T,AFP,HCG or LDH or semen parameters were observed during the follow-up as compared with the baseline.Natural conception was achieved in 2 cases at 16 and 18 months re-spectively after surgery.Conclusion:BTT can be differentially diagnosed by CDFI and MRI before surgery and confirmed by histo-pathology.TSMS can achieve complete excision of the tumor,maximal sparing of the normal testis tissue and thereby effective preserva-tion of male fertility.

Orthostatic hypotension (OH) is the most prominent autonomic neurodysfunction in patients with multiple system atrophy (MSA). Dementia and cognitive fluctuations at early course of the disease remain the exclusion criteria for MSA, however, increased studies have indicated that mild cognitive impairment is prevalent in MSA. OH is associated with an increased risk of cognitive dysfunction in patients with Parkinson's disease (PD) due to recurrent cerebral hypoperfusion, and earlier, more prevalent and more severe OH occurs in MSA patients than that in PD patients; therefore, could OH serve as a modifier to improve cognitive dysfunction in MSA patients? Do the two interact as both cause and effect, or do they share a common neurobiological basis? This paper reviews the influence of OH in cognitive dysfunction in MSA patients, and summarizes the existing problems and looks forward to future research directions, with a view to enhance clinicians' understanding of OH and cognitive dysfunction in MSA patients.

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

Purpose To evaluate the effect of PCSK9 gene knockout on myocardial function in obese mice via ultrasound strain technology,and to discuss the related mechanisms.Materials and Methods Twenty six-week-old wild-type C57BL/6 male mice were selected and randomly divided into a normal group(n=10)and an obese group(n=10).Additionally,ten six-week-old PCSK9-/-C57BL/6 male mice were selected as the PCSK9-/-group.Mice in the obese group and PCSK9-/-group were fed with high-fat feed to create models,while those in the normal group were fed with regular feed.After 12 weeks,mice that were successfully modeled were selected from the obese group and PCSK9-/-group.Then,the three groups of mice were subjected to cardiac ultrasound,transmission electron microscopy and immunofluorescence staining to observe relevant indicators.Results The interventricular septal end-diastolic thickness of mice in obese group,normal group,and PCSK9-/-group were(0.98±0.13)mm,(0.77±0.07)mm,(0.78±0.13)mm,respectively,with statistically significant difference(F=5.10,P=0.02).The obese group was thicker than the normal group(t=2.73,P＜0.05),while the PCSK9-/-group was thinner than the obese group(t=-2.92,P＜0.05).There were statistically significant differences in global longitudinal strain and global circumferential strain of the left ventricle among the three groups(F=7.44,15.40,P＜0.05),with the obese group showing a decrease in global longitudinal strain and global circumferential strain compared to the normal group(t=3.79,5.50,P＜0.05).The PCSK9-/-group showed an increase in global longitudinal strain and global circumferential strain compared to the obese group(t=-2.53,-3.37,P＜0.05).Electron microscopy and immunofluorescence results showed that the myocardial ultrastructure of the obese group was damaged,and the expression of NLRP3 and Caspase-1 were higher than that of the normal group(t=12.53,-4.73,P＜0.05),the myocardial ultrastructure damage in the PCSK9-/-group was significantly improved,the expression of NLRP3 and Caspase-1 were lower than that in the obese group(t=-6.23,2.05,P＜0.05).Conclusion Ultrasound strain can more sensitively detect changes in myocardial function in obese mice with PCSK9 gene knockout compared with conventional cardiac ultrasound parameters.Knockout of the PCSK9 gene may improve myocardial function in obese mice by inhibiting the expression of NLRP3 and Caspase-1.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.