ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.

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.

This study was aimed at investigating the antimicrobial susceptibility and genomic characteristics of multidrug resistant diarrheagenic Escherichia coli isolated from human and food samples in Henan Province from 2017 to 2022.A total of 101 strains of multidrug resistant diarrheagenic E.coli were subjected to antimicrobial susceptibility testing with the broth di-lution method.Whole genome sequencing was performed to analyze the antimicrobial resistance genes,multilocus sequence typ-ing,and plasmid types.The sequencing data were used to construct a phylogenetic tree based on core genome single-nucleotide polymorphisms(cgSNPs).The isolates showed the highest resistance to ampicillin(87.1％),followed by tetracycline(79.2％)and nalidixic acid(64.4％).The resistance rate to cefotaxime was 38.6％.All 101 strains were classified into 60 STs,among which ST10,ST1491,and ST38 were dominant.Moreover,23 distinct plasmid replicons were identified,among which IncFIB was dominant.Diverse antimicrobial resistance genes(including quinolone,aminoglycoside,β-lactamase,and tetracycline)were identified.Insertion sequences(IS26,IS903B,and ISECP 1)were identified in upstream and downstream analysis of the gene context of the extended-spectrum β-lactamase bla CTX-M-14 and bla CTX-M-55 genes.In conclusion,multidrug resistant diarrhea-genic Escherichia coli isolated from clinical and food samples in Henan Province showed high genetic diversity and high antimi-crobial resistance.The dissemination of blaCTX-M carried by the strains was shown to be associated with the insertion sequence(IS).

Objective:To investigate the incidence of PTPN11 gene mutation and its associated gene mutations in adult patients with acute myeloid leukemia(AML),and analyze its clinical characteristics.Methods:Second-generation sequencing and Sanger sequencing were used to detect 51 gene mutations,and multiplex-PCR was used to detect 41 fusion genes from 451 newly diagnosed adult AML patients admitted to Affiliated Hospital of Jiangnan University,Changzhou Second People's Hospital,Wuxi People's Hospital and Wuxi Second People's Hospital from January 2017 to July 2022.Results:Among 451 primary adult AML patients,the PTPN11 gene mutation was detected in 34 cases,and the mutation rate was 7.5％.In the 34 patients,37 PTPN11 alterations were found,which were exclusively missense mutations affecting residues located within the N-SH2(31 cases)and PTP(6 cases)domains and clustered overwhelmingly in exon 3.The platelet count of PTPN11 mutation patients was 76.5(23.5,119.0)× 109/L,which was significantly higher than 41.0(22.0,82.5)×109/L of wild-type patients(P＜0.05).While,there were no significant differences in sex,age,peripheral white blood cell count,hemoglobin,and bone marrow blast between PTPN11 mutation and wild-type patients(P＞0.05).In FAB subtypes,PTPN11 mutations were mainly distributed in M5,followed by M2 and M4,less frequently in M3 and M6.There was no significant difference in the distribution of FAB subtypes between PTPN11 mutation and wild-type patients(P＞0.05).A total of 118 AML patients were detected positive fusion gene,among which patients with PTPN11 mutations had a higher incidence of positive MLL-AF6 than wild-type ones(P＜0.01).97.1％of 34 patients with PTPN11 mutations were accompanied by other mutations,in descending order,they were respectively NPM1(38.2％),NRAS(32.4％),FLT3-ITD(32.4％),DNMT3A(32.4％)and KRAS(23.5％),etc.Conclusion:PTPN11 mutation has a certain incidence in AML patients and is clustered overwhelmingly in exon 3.ALL of them are exclusively missense mutations,and most often present in conjunction with NPM1 mutations.FAB typing of PTPN11 mutation is mostly manifested as M5 subtype,which is associated with higher platelet counts.

Objective:To establish a model to predict the overall survival(OS)rate of patients with diffuse large B-cell lymphoma(DLBCL)based on systemic inflammatory indicators,and study whether the new model combined with inflammatory related parameters is more effective than the conventional model using only clinical factors to predict the OS of patients with DLBCL.Methods:The clinical data of 213 patients with DLBCL were analyzed retrospectively.Backward stepwise Cox regression analysis was used to screen independent prognostic factors related to OS,and a nomogram for predicting OS was constructed based on these factors.Akaike information criterion(AIC)and Bayesian information criterion(BIC)were used to evaluate the fitting of the model,the consistency index(C-index),area under receiver operating characteristic(ROC)curve(AUC)and calibration curve were used to evaluate the prediction accuracy of nomogram,and decision curve analysis(DCA)and Kaplan Meier curve were used to evaluate the clinical practicability of nomogram.Results:Multivariate analysis confirmed that age,ECOG PS score,serum lactate dehydrogenase(LDH)level,systemic immune inflammatory index(SII),and prognostic nutritional index(PNI)were used to construct the nomogram.The AIC and BIC of the nomogram were lower than the International Prognostic Index(IPI)and the National Comprehensive Cancer Network(NCCN)-IPI,indicating that the nomogram had better goodness of fit.The C-index and AUC of the nomogram were higher than IPI and NCCN-IPI,indicating that the prediction accuracy of the nomogram had been significantly improved,and the calibration curve showed that the prediction results were in good agreement with the actual survival results.DCA showed that the nomogram had better clinical net income.Kaplan Meier curve showed that patients could be well divided into low-risk,medium-risk and high-risk groups according to the nomogram score(P＜0.001).Conclusion:The nomogram combined with inflammatory indicators can accurately predict the individual survival probability of DLBCL patients.

Objective To explore the impact of artificial intelligence(AI)-assisted computing systems on the success rate of surgery,stereoscopic vision,and quality of life in patients with intermittent exotropia.Methods A total of 108 children(216 eyes)with intermittent exotropia who visited Ziyang Hospital of West China Hospital,Sichuan University from March 2021 to April 2023 were collected and randomly divided into Group A and Group B,with 54 children(108 eyes)in each group.Group A used the traditional calculation method,while Group B used the AI-assisted calculation method to determine the surgical volume of strabismus in children by the angles of strabismus at 6m and 33 cm.The success rate of surgery,postoperative angle of strabismus,stereoscopic visual function,horizontal and vertical perceptual eye positions,and quality of life[Child Intermittent Exotropia Questionnaire(CIXTQ)score]were compared between the two groups at 1 day,1 month,3 months and 6 months after surgery.Results At 1 day,1 month,3 months and 6 months after surgery,the success rate of surgery in Group B was significantly higher than that in Group A(all P＜0.05).Compared with the val-ues at 1 day after surgery,the angles of strabismus at 6 m and 33 cm in the two groups were significantly reduced at 1 month,3 months and 6 months after surgery(all P＜0.05);Group B had significantly lower angles of strabismus at 6 m and 33 cm than Group A at 1 day,1 month,3 months and 6 months after surgery(all P＜0.05).At 1 month,3 months and 6 months after surgery,the central and far stereoscopic visions of children in the two groups gradually increased,with the increase rate in Group B being significantly higher than that in Group A(Finter-group=76.59,P＜0.05);the proportion of children without stereoscopic vision in both groups gradually decreased,with a decrease rate in Group B being significantly higher than that in Group A(Finter-group=137.74,P＜0.05).At 1 month,3 months and 6 months after surgery,the horizon-tal and vertical perceptual eye positions in Group B showed a significant descend range compared with those in Group A(all P＜0.05).At 1 day,1 month,3 months and 6 months after surgery,the exotropia displacement of children in both groups gradually increased,and the displacement of children in Group B was significantly smaller than that in Group A at 1 month,3 months and 6 months postoperatively(all P＜0.05).At 1 month,3 months and 6 months after surgery,the CIX-TQ scores of children in the two groups increased gradually,with CIXTQ scores in Group B being significantly higher than those of Group A(all P＜0.05).Conclusion AI-assisted computing systems can effectively improve the success rate of intermittent exotropia surgery,enhance the establishment of stereoscopic visual function,improve visual quality,and sig-nificantly improve the quality of life of children.

Objective Visual electrophysiology and optical correlation tomography angiography(OCTA)were used to investigate differences in preoperative retinal function in patients with type 2 diabetic cataract(DC)without obvious retinopathy(NDR)and to determine the clinical application of whole-process blood glucose man-agement(WBGM)for improving postoperative vision in DC patients.Methods This study investigated the preop-erative and postoperative visual electrophysiology(N75,P100,photopic FERG,and scotopic FERG),peripapil-lary retinal nerve fiber layer(pRNFL)and peripapillary capillary vessel density(ppVD)data,as well as trends in these data changes during blood glucose management intervention.Results As the course of T2DM progressed,FBG and HbA1c increased,the N75 and P100 lategraduancy periods of patients gradually lengthened,and the photopic FERG,scotopic FERG,pRNFL,and ppVD values decreased at each postoperative time point.At the same time,the best corrected visual acuity(BCVA)of patients after surgery gradually decreased(P<0.05).Compared with that at 1 week after surgery,the BCVA of Group A(without whole-process blood glucose manage-ment)gradually increased at 1 month and 3 months after surgery but showed a downward trend at 1 year after sur-gery.The BCVA of Group B(with whole-process blood glucose management)gradually stabilized at 1 month after surgery,and at all time points after surgery,the BCVA of Group B was better than that of Group A.The results showed that N75 and P100 in Group A were greater than those in Group B,while the photopic and scotopic FERG,pRNFL,and ppVD(%)in Group A were lower than those in Group B.In addition,N75 and P100 in Group A showed a gradual prolongation trend at various time points after surgery,while photopic FERG,scotopic FERG,pRNFL,and ppVD(%)showed a gradually decreasing trend.However,the above data in Group B gradu-ally stabilized at 3 months after DC surgery,approaching the preoperative level of the group(P<0.05).In the state of whole blood glucose management,although N75 and P100 both reached their longest durations at 1 week af-ter surgery,N75,P100,photopic FERG,scotopic FERG,and pRNFL showed a gradually decreasing trend at 1 month and 3 months after surgery,while ppVD(%)gradually increased(P<0.05).At various time points from 3 months to 1 year after surgery,the overall trend of the above indicators remained stable and close to the preoperative values(P>0.05).Conclusion According to the results of the quantitative analysis of visual electrophysiology and OCTA,in DC patients without obvious retinopathy and with the worsening of diabetes,retinal function decreased,but whole-process blood glucose management effectively restored retinal function and improved visual quality after surgery.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Mutations in myosin heavy chain 7(MYH7)and myosin binding protein C3(MYBPC3)genes encoding thick filaments are the main cause of hypertrophic cardiomyopathy(HCM),while a small part of HCM is caused by mutations of troponin C1,slow skeletal and cardiac type(TNNC1),troponin T2,cardiac type(TNNT2),troponin I3,cardiac type(TNNI3),actin alpha cardiac muscle 1(ACTC1),and tropomyosin 1(TPM1)genes encoding thin filaments.In this review,we mainly introduce the detailed mechanism and research status of HCM caused by mutations of the gene encoding cardiomyocyte sarcomere in the past few years,in order to provide reference for further study of the pathogenesis and treatment of HCM.