Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

The Compilation Instructions for Expert Consensus on Clinical Application of Dieda Huoxue capsules systematically expound the development methods and evidence-based basis of this consensus. In view of the weak clinical application evidence and ambiguous indications of Dieda Huoxue capsules， the Institute of Basic Research in Clinical Medicine of the China Academy of Chinese Medical Sciences and Wangjing Hospital took the lead and collaborated with 33 experts from 28 medical institutions nationwide. They strictly followed the World Health Organization （WHO） guideline-making norms and the Grading of Recommendations Assessment， Development and Evaluations （GRADE） evidence-grading system and completed the compilation through multidisciplinary cooperation. The workflow included constructing clinical questions （19 items were screened by the nominal group technique）， retrieving evidence （from Chinese and English databases and grey literature）， assessing safety （integrating drug monitoring data and clinical investigations）， and forming recommendations and consensus suggestions （3 recommendations were reached via the GRADE grid method， and 16 consensus suggestions were reached by the majority vote rule）. The results indicate that the consensus clearly states that this medicine （Dieda Huoxue capsules） is applicable to conditions like traumatic injury， blood stasis-induced pain， and sudden lumbar sprains. The recommended dose is 6 capsules each time， twice a day. Combining oral administration with external application can enhance the efficacy， and elderly patients should take the medicine at intervals. Safety monitoring suggests that it should be used with caution in people with a bleeding tendency and those with an allergic constitution. The compilation process involved three rounds of reviews by internal and external experts. Literature analysis， the Delphi method， and clinical applicability tests were employed to ensure methodological rigor. The compilation instructions comprehensively present key aspects such as project approval and registration， conflict-of-interest statements， and evidence evaluation through 12 appendices， providing methodological support for the clinical translation of the consensus. In the future， it will be continuously improved through a dynamic revision mechanism.

OBJECTIVE: To determine risk factors for cutout failure in geriatric intertrochanteric fracture patients after cephalomedullary nail fixation. METHODS: A retrospective review of 518 elderly patients who underwent cephalomedullary nail fixation for intertrochanteric fractures between January 2008 and August 2018 was conducted, including 167 males and 351 females, age from 65 to 97 years old. All patients were followed up for at least one year after surgery and divided into a healed group and a cutout group based on whether the hip screw cutout occurred. Among all patients, 10 cases experienced hip screw cutout. The general information, surgical data, and radiological data of the two groups were compared, and risk factors influencing hip screw cutout were analyzed. Propensity score matching was then performed on the cutout group based on gender, age, body mass index(BMI), and American Society of Anesthesiologists(ASA), and 40 patients from the healed group were matched at a ratio of 1∶4. Key risk factors affecting hip screw cutout were further analyzed. Multivariable logistic regression analysis was conducted to evaluate associations between variables and cutout failure. RESULTS: There were no statistically significant differences between the healed group and the cutout group in terms of age, gender, BMI, ASA, and AO classification. However, statistically significant differences were observed between the two groups in terms of reduction quality(P=0.003) and tip-apex distance(TAD), P<0.001. Multivariate analysis identified poor reduction quality OR=23.138, 95%CI(2.163, 247.551), P=0.009 and TAD≥25 mm OR=30.538, 95%CI(2.935, 317.770), P=0.004 as independent risk factors for cutout failure. CONCLUSION The present study identified poor reduction quality and TAD≥25 mm as factors for cutout failure in geriatric intertrochanteric fractures treated with cephalomedullary nails. Further studies are needed to calculate the optimal TAD for cephalomedullary nails.
Humans ; Male ; Female ; Hip Fractures/surgery* ; Aged, 80 and over ; Aged ; Risk Factors ; Retrospective Studies ; Fracture Fixation, Intramedullary/adverse effects* ; Bone Nails ; Bone Screws

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To observe the effect of minocycline hydrochloride ointment combined with metronidazole rod on soft tissue inflammation in patients with oral peri-implantitis.Methods Patients with oral peri-implantitis were divided into control group and treatment group according to cohort method.The patients in the two groups were treated with the same routine treatment such as supragingival scaling,supragingival scaling and local containing Kangfuxin solution(10 mL each time,qd).On this basis,the patients in the control group were placed with metronidazole rod in the periodontal pocket,once every 2 days.The treatment group was filled with minocycline hydrochloride ointment in the periodontal pocket on the basis of the control group,once a week;both groups were treated for 2 weeks.The clinical efficacy,periodontal related indexes[modified plaque index(mPLI),clinical attachment loss(CAL),modified sulcus bleeding index(mSBI)and probing depth(PD)],gingival crevicular fluid cytokines[interleukin-6(IL-6),IL-8,IL-1β,matrix metalloproteinase-8(MMP-8)]before and after treatment were compared between the two groups;and the safety was evaluated.Results The treatment group and the control group were included in 38 and 42 cases,respectively.The total effective rates of the treatment group and the control group were 94.74％(36 cases/38 cases)and 76.19％(32 cases/42 cases),respectively,and the difference was statistically significant(P＜0.05).After treatment,the mPLI of treatment group and control group were(0.77±0.10)and(1.23±0.15)points,respectively;CAL were(1.18±0.16)and(2.74±0.31)mm,respectively;mSBI were(1.23±0.17)and(1.71±0.18)points,respectively;PD were(1.97±0.20)and(2.25±0.24)mm,respectively;IL-6 were(2.04±0.26)and(4.01±0.42)ng·mL-1,respectively;IL-8 were(4.01±0.42)and(7.00±0.73)ng·mL-1,respectively;IL-1β were(1.64±0.17)and(2.04±0.21)ng·mL-1,respectively;MMP-8 were(1.02±0.14)and(1.68±0.17)ng·mL-1,respectively.The above indexes in the treatment group were significantly different from those in the control group(all P＜0.05).The adverse drug reactions in the two groups mainly included nausea and vomiting,abdominal pain and diarrhea,and dizziness.The total incidence of adverse drug reactions in the treatment group and the control group were 34.21％(13 cases/38 cases)and 21.43％(9 cases/42 cases),and the difference was not statistically significant(P＞0.05).Conclusion Minocycline hydrochloride ointment combined with metronidazole rod is effective in the treatment of oral peri-implantitis,which can effectively improve the periodontal health status,significantly reduce the body's inflammatory damage,and has good safety.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.