Objective To analyze the clinical efficacy of valve surgeries for infective endocarditis and the affecting factors, and compare the early- and long-term postoperative outcomes of different surgery approaches. Methods The patients with infective endocarditis who underwent valve replacement/valvuloplasty in our hospital from 2010 to 2022 were retrospectively collected. The clinical data of the patients were analyzed. Results A total of 343 patients were enrolled, including 197 patients with mechanical valve replacement, 62 patients with bioprosthetic valve replacement, and 84 patients with valvuloplasty. There were 238 males and 105 females with an average age of (44.2±14.8) years. Single-valve endocarditis was present in 200 (58.3%) patients, and multivalve involvement was present in 143 (41.7%) patients. Sixty (17.5%) patients had suffered thrombosis before surgery, including cerebral embolisms in 32 patients. The mean follow-up time was (60.6±43.8) months. Early mortality within one month after the surgery occurred in 17 (5.0%) patients, while later mortality occurred in 19 (5.5%) patients. Eight (2.3%) patients underwent postoperative dialysis, 13 (3.8%) patients suffered postoperative stroke, 6 patients underwent reoperation, and 3 patients suffered recurrence of infective endocarditis. Smoking (P=0.002), preoperative embolisms (P=0.001), duration of surgery (P=0.001), and postoperative dialysis (P=0.001) were risk factors for early mortality, and left ventricular ejection fraction ≥60% (P=0.022) was protective factor for early mortality. New York Heart Association classification Ⅲ-Ⅳ (P=0.010) and ≥3 valve procedures (P=0.028) were risk factors for late mortality. The rate of composite endpoint events was significantly lower in the valvuloplasty group than that in the valve replacement group. Conclusion For patients with infective endocarditis, smoking and preoperative embolisms are associated with high postoperative mortality, multiple-valve surgery is associated with a poorer prognosis, and valvuloplasty has advantages over valve replacement and should be attempted in the surgical management of patients with infective endocarditis.

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To investigate the effects of trigonelline combined with aerobic exercise on hyperlipidemia rats and its mechanism.Methods SD rats were randomly divided into control group(normal diet),model group(hyperlipidemia rat model was established by feeding high fat diet),experimental-L,-H groups(high fat diet+15,45 mg·kg-1 trigonelline)and combine group(high fat diet+45 mg·kg-1 trigonelline+aerobic exercise).Each group had 11 rats.Serum lipid metabolism related indexes were detected by automatic biochemical analyzer.Serum levels of 6 ketone prostaglandin F1a(6-keto-PGF1a);the levels of glutamic oxaloacetic transaminase(GOT)in liver tissue were detected by enzyme-linked immunosorbent assay;the mRNA levels of interleukin-1β(IL-1β)in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR);Western blot assay was used to detect the expression of proprotein convertase subtilin/kexin 9 type(PCSK9)and low density lipoprotein receptor(LDLR)protein in liver tissue.Results The serum TC levels in control group,model group,experimental-L group,experimental-H group and combine group were(1.81±0.10),(6.68±0.77),(5.10±0.44),(3.57±0.47)and(2.40±0.35)mmol·L-1;the levels of 6-keto-PGF1a were(841.47±86.74),(536.03±36.50),(664.06±52.44),(759.19±52.30)and(824.45±67.62)pg·mL-1;GOT levels were(11.95±0.88),(18.20±1.81),(15.05±1.10),(13.32±0.98)and(12.47±0.83)U·L-1;IL-1β mRNA expression levels were 1.00±0.09,2.21±0.17,1.57±0.10,1.26±0.16 and 1.14±0.09;the expression of PCSK9 protein were 0.39±0.07,0.88±0.08,0.71±0.08,0.60±0.04 and 0.52±0.07;LDLR protein levels were 1.12±0.13,0.52±0.07,0.74±0.11,0.84±0.08 and 0.96±0.11,respectively.Model group was compared with the control group,experimental-L group and experimental-H group were compared with model group respectively,combine group was compared with the experimental-H group,the differences of the above indexes were statistically significant(all P＜0.05).Conclusion Trigonelline combined with aerobic exercise may inhibit the expression of PCSK9 and up-regulate the expression of LDLR to improve lipid metabolism,so as to play a lipid-lowering role in hyperlipidemia rats.

Objective To investigate the effect and mechanism of rosuvastatin on liver injury induced by high fat diet in hyperlipidemia rats.Methods All rats were randomly divided into control group,model group and experimental group,with 10 rats in each group.Except the control group,hyperlipidiosis model rats were fed with high-fat diet combined with alcohol to construct hyperlipidiosis model rats.The experimental group was given 10 mg·kg-1 rosuvastatin by gavage,control group and model group were given gavage with 10 mL·kg-1 distilled water,once a day for 4 weeks.Serum lipids and liver function were measured by enzyme-linked immunosorbent assay(ELISA).Quantitative real-time polymerase chain reaction(qRT-PCR)was used to analyze the expression of microRNA(miR)-185-3p and mastermind like transcription coactivator 1(MAML1);the expression levels of MAML1 and inducible nitric oxide synthase(iNOS)were detected by Western blot.Results The liver tissue injury scores of control group,model group and experimental group were 0.32±0.15,4.03±1.62 and 2.36±1.14;the TG levels were(4.95±0.86),(6.75±1.42)and(5.51±0.91)mmol·L-1;the TC were(2.36±0.48),(5.11±2.05)and(3.24±1.39)mmol·L-1;the LDL-C were(0.67±0.16),(1.73±0.42)and(1.03±0.25)mmol·L-1;the HDL-C were(0.72±0.23),(0.51±0.14)and(0.64±0.11)mmol·L-1;the GOT were(158.31±32.46),(253.19±49.27)and(187.52±53.46)U·L-1;the GPT values were(53.17±6.81),(79.64±13.92)and(55.63±9.11)U·L-1.Compared with the control group,the expression of miR-185-3p in the model group was significantly down-regulated,the expression of MAML1 and iNOS was significantly increased.Compared with the model group,the expression of miR-185-3p in the liver tissue of experimental group was significantly up-regulated,while the expression of MAML1 and iNOS was significantly decreased(all P＜0.05).There were statistically significant differences in the above indexes between the control group and the model group(P＜0.05);the above data in the model group were statistically significant compared with the experimental group(P＜0.05).Conclusion Rosuvastatin inhibits the expression of MAML1 and iNOS by regulating miR-185-3p,thereby improving the liver injury induced by hyperlipidemia in rats.

Objective To investigate the effect of naringin on hyperlipidemia in mice and to elucidate its mechanism.Methods C57BL/6 mice were randomly divided into control group,hyperlipidemia group and naringin group.Mice in hyperlipidemia group and naringin group were fed high-fat diet for 4 weeks,and hyperlipidemia model was established.The control group was fed normal diet.After successful modeling,naringin group mice were intragastric with 200 mg·kg-1 naringin per day,and mice in control group and hyperlipemia group were intragastric with 0.9％NaCl per day for 5 weeks.The blood of mice was collected for lipid detection.The activities of superoxide dismutase(SOD)and catalase(CAT)and the contents of malondialdehyde(MDA)and glutathione(GSH)were detected by biochemical method.Western blot was used to detect the protein expression.Results The activity of SOD in liver tissue of mice in control group,hyperlipidemia group and naringin group were(58.43±6.27),(37.16±4.10)and(51.23±4.81)U·mg prot-1,respectively;CAT activities were(176.11±13.59),(112.65±10.02)and(158.46±14.37)U·mg prot-1,respectively;the contents of MDA were(3.15±0.74),(12.62±2.07)and(5.76±1.83)U·mg prot-1;the contents of GSH were(91.52±11.47),(34.16±4.62)and(71.64±8.79)U·mg prot-1,respectively;the relative protein expression levels of induced nitric oxide synthase(iNOS)were 0.28±0.05,4.26±1.13 and 0.94±0.19;the relative protein expression levels of adenosine 5'-monophosphate activated protein kinase(AMPK)were 1.32±0.18,0.84±0.11 and 1.49±0.16,respectively;the relative protein expression levels of cholesterol regulatory element binding protein(SREBP)were 1.76±0.24,5.78±1.21 and 2.93±0.42;the relative protein expression levels of 3-hydroxy-3-methyl glutaryl coenzyme A reductase(HMGCR)were 1.69±0.18,6.13±1.38 and 3.26±0.43,respectively.The above indexes in the control group and the naringin group were significantly different from those in the hyperlipidemia group(P＜0.05,P＜0.01,P＜0.001).Conclusion Naringin can effectively regulate the level of blood lipids,inhibit oxidative stress and apoptosis in hyperlipidemia mice,and its mechanism may be related to the regulation of AMPK/HMGCR/SREBP signaling pathway.

The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of diseases.Thioesterase superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding proteins.Some studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its phosphorylation.Initially,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous findings.Considering these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially cancer.This work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.