Objective To explore the potential mechanism of Xinnao Maikang in improving ApoE-/-atherosclerosis mice based on PPARγ/LXRα/ABCA1 pathway.Methods Totally 50 ApoE-/-mice were randomly divided into model group,atorvastatin group,Xinnao Maikang high-,medium-and low-dosage groups,and fed with high-fat diet for 12 weeks to establish atherosclerosis model.Another 10 C57BL/6J mice were selected as normal group,and atorvastatin group was given atorvastatin calcium suspension by intragastric administration,Xinnao Maikang high-,medium-and low-dosage groups were given Xinnao Maikang Decoction 56,28,14 g/kg by intragastric administration,the normal group and model group were given equal volume of normal saline by intragastric administration for 8 weeks.Liver index of mice was detected,serum lipid level of mice was detected by automatic biochemical analyzer,TC and TG contents in liver tissue were detected by biochemical kit,morphology of aortic intima and liver tissue were observed by HE staining,lipid deposition in liver tissue was observed by oil red O staining,the expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue were detected by Western blot.Results Compared with the normal group,the liver index in the model group significantly increased(P<0.05),the contents of serum TC,TG and LDL-C significantly increased(P<0.05),and the contents of HDL-C significantly decreased(P<0.05),the contents of TC and TG in liver tissue increased(P<0.05),the aortic wall was thickened,the number of subcutaneous foam cells increased,the arrangement of liver cells were disaffected,and a large number of fat vacuoles could be seen,the protein expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue significantly decreased(P<0.01).Compared with the model group,the liver index of Xinnao Maikang high-,medium-and low-dosage groups and atorvastatin group significantly decreased(P<0.05),the serum contents of TC,TG and LDL-C significantly decreased(P<0.05),and the HDL-C contents significantly increased(P<0.05),the contents of TC and TG in liver tissue significantly decreased(P<0.05),the aortic wall thickened and the subcutaneous foam cells decreased,the liver cells were arranged neatly,and fat degeneration was reduced to varying degrees,the protein expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue of Xinnao Maikang high-dosage group and atorvastatin group significantly increased(P<0.05,P<0.01).Conclusion Xinnao Maikang can decrease blood lipid level,reduce atherosclerotic plaque and reduce lipid deposition in liver of atherosclerotic mice,and its mechanism may be related to regulating PPARγ/LXRα/ABCA1 pathway,regulating lipid metabolism,promoting reverse cholesterol transport.

To achieve rapid and visual detection of Plasmodium vivax,a detection method based on recombinase polymerase amplification(RPA)technology and lateral flow dipstick(LFD)was established and evaluated.Targeting the conserved sequence of the P.vivax 18S rRNA gene(GenBank:DQ660817.1)as the target sequence,primers and probes were designed with Primer Premier 5,and the P.vivax recombinant plasmid(pUCPv)was constructed as the standard.A sensitive and specific RPA-LFD-based rapid visual detection method for P.vivax nucleic acids was established.The plasmid standard was serially diluted 10-fold to concentrations of 1×103,1×102,1×101,1×10?,and 1×10?1 copies/μL for sensitivity testing.To evaluate specificity,whole blood DNA samples from patients infected with Plasmodium falciparum,Plasmodium malariae,Plasmodium ovale,or Leishmania donovani,as well as healthy participants,were tested by RPA-LFD.Additionally,The assay′s accuracy was evaluated by testing whole blood DNA samples from 24 confirmed P.vivax-infected patients.This study successfully established a sensitive,specific,and rapid visual RPA-LFD method for detecting P.vivax nucleic acids.The assay can complete P.vivax detection within 20 minutes under isothermal conditions at 39 ℃,achieving a sensitivity of 1 copy/μL.There is no significant cross reaction with parasites such as other Plasmodium species and L.donovani,and the specificity is 100%.All 24 DNA samples from confirmed P.vivax patients were detected,showing a 100%detection rate.The developed RPA-LFD assay exhibits excellent sensitivity and specificity,requires only simple heating equipment,and is user-friendly.This rapid visual detection method is particularly suitable for P.vivax screening in low-resource settings.

Objective To explore the impact of"knowledge-attitude-practice"(KAP)training mode on head nur-ses' core competency in healthcare-associated infection(HAI)prevention and control in a tertiary first-class general hospital.Methods Head nurses of 113 departments in a tertiary first-class general hospital were taken as the re-search objects.Guided by problems and demands,HAI training was conducted using the KAP training mode.The training was divided into two stages:a stage with problems of infection control and investigation of knowledge de-mands,as well as a stage with KAP training mode implementation.It included theoretical lectures,visits and lear-ning,and supervision on rectification.Scores of theory,supervision,and core competency of head nurses before training,1 month and 6 months after training were compared by the analysis of variance.SPSS 26.0 statistical soft-ware was used for analysis.Results The top three infection control problems in this hospital were hand hygiene,prevention and control of infection with multidrug-resistant organisms,as well as HAI prevention and control in the wards.The top three training modules required urgently by the head nurses were occupational exposure and self-protection,principles of medical waste disposal,as well as prevention and control of HAI in the wards.Both scores of theory and supervision after training were higher than those before training,with statistically significant diffe-rences(both P＜0.01).The core competencies of the head nurses were at a high level.After implementing KAP training mode,the scores of dimensions in critical thought and research,clinical nursing,leadership,and profe-ssional development,as well as the overall score of core competencies were all higher than before training.Diffe-rences were all statistically significant(all P＜0.05).The overall scores of dimensions in legal and ethical practice,education and consultation,as well as interpersonal relationship were all higher than before training,but the diffe-rences were not statistically significant(all P＞0.05).Conclusion KAP training mode can significantly improve the scores of theory,supervision,and core competencies of head nurses,and can be further promoted and applied in head nurses' infection control training.

BACKGROUND:Developmental dysplasia of hip causes groin pain in patients with prolonged activity or standing due to the presence of deformities of the acetabulum and femoral head in terms of structure,size and orientation,and if not effectively treated,patients' normal activities will be severely limited.OBJECTIVE:Finite element model of the hip joint of solid-liquid biphase fiber reinforced cartilage based on FEBio was established to explore the biomechanical properties of the cartilage for patients with developmental dysplasia of hip and the normal hip joint.METHODS:A patient with developmental dysplasia of hip and a normal volunteer were chosen to build their left hip models including left pelvis,left femur,and cartilage attached thereto. The solid-liquid biphase fiber reinforced cartilage of normal hip was verified to be effective. The cartilage equal contact stress,fluid pressure,solid effective stress,and fluid support rate differences between the developmental dysplasia of hip patients hip and the normal one in the case of one leg of static load (2130 N) were compared after establishing finite element models of developmental dysplasia of hip patients.RESULTS AND CONCLUSION:(1) Compared with the finite element results of the normal hip model,the cartilage contact position of developmental hip dysplasia patient hip showed obvious edge contact,the peak contact stress (3.86 Mpa) and peak fluid pressure (3.76 Mpa) were both higher than normal hip model. (2) After 1500 s (stable load-bearing capacity),peak contact stress and peak fluid pressure in both models decreased,but the cartilage contact position of developmental hip dysplasia patient hip moved from the edge of cartilage to the center,and fluid support rate decreased from 97.41％ to 91.08％. The fluid support rate in normal hip was decreased by 0.58％ from 95.24％ to 94.66％. (3) It is indicated that under the physiological load of standing on one leg,the cartilage of developmental dysplasia of hip patients showed obvious edge load,and the decrease of peak contact stress,fluid pressure,and fluid formation rate was greater than that of normal cartilage. Considering the solid-liquid biphasic fiber reinforcement characteristics of cartilage,it is of great clinical significance to evaluate the biomechanical properties of hip cartilage in developmental dysplasia of hip patients,to understand the pathophysiological mechanism of developmental dysplasia of hip,and make preoperative plan.

Objective:To compare the efficacy of various machine learning models in predicting renal function decline after robot-assisted partial nephrectomy(RAPN),and to provide evidence for clinical risk stratification.Methods:This study retrospectively in-cluded the clinical data of 733 patients with renal cell carcinoma undergoing RAPN at the Urology Department of The First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023.Demographic characteristics,laboratory indicators,and perioperative parameters were integrated to construct seven machine learning models.Key predictors were interpreted using Shap-ley additive explanations(SHAP).Model performance was evaluated using the area under the receiver operating characteristic curve(AUC).Results:The random forest model demonstrated the best predictive performance(AUC=0.84).SHAP analysis identified neutrophil-to-lymphocyte ratio,tumor diameter,the international normalized ratio of prothrombin time,white blood cell count,and in-traoperative blood loss as significant factors influencing postoperative renal function decline.Conclusion:This study provides a poten-tial predictive tool for clinical practice,aiding in identifying high-risk patients and optimizing postoperative management strategies.

Objective To investigate the interaction between a novel antimicrobial compound,HL-J6,and penicillin-binding protein 1(PBP1)of Staphylococcus aureus.Methods With MRSA252 genomic DNA as the template and PBP1F and PBP1R as primers,the expression plasmid pET30a-pbp1-39-608 was constructed by amplifying the target gene fragment followed by cloning into the Nde I/Xho I restriction sites of the pET30a vector.Then the obtained plasmids were transformed into Escherichia coli for the expression of PBP1-39-608 protein,and the product was purified by affinity chromatography.The inhibitory effect of HL-J6 on the transpeptidase activity of PBP1-39-608 was measured using peptidoglycan side chain backbone peptide,with thiol ester analog S2d as the substrate.The affinity between HL-J6 and PBP1-39-608 was detected using microscale thermophoresis(MST),and the binding interaction was confirmed by cellular thermal shift assay(CETSA).Molecular docking and dynamics simulation were performed using AutoDock Vina and Desmond software,respectively,to elucidate the binding mode of HL-J6 with the PBP1-39-608 protein and the key amino acid residues involved.Results The recombinant plasmid pET30a-pbp1-39-608 was successfully constructed,and PBP1-39-608 protein was produced after induction and purified,yielding a protein with an approximate molecular mass of 65×103.HL-J6 inhibited the transpeptidase activity of PBP1-39-608 in a time-dependent manner(P<0.001).The dissociation constant Kd of the binding between HL-J6 and PBP1-39-608 was 64.92 μmol/L.Molecular docking results showed that HL-J6 bound to the active pocket of PBP1-39-608 by interacting with key residues such as ILE-348,ASN-370,THR-516 and PHE-423,with a binding score of-8.38 kcal/mol(<-5.00 kcal/mol).Dynamics simulation results indicated that the complex became stable after 50 ns.Conclusion HL-J6 effectively inhibits the transpeptidase activity of Staphylococcus aureus PBP1,and shows stable interaction with the protein.

Objective:To evaluate the role of the CC chemokine ligand 2/CC chemokine receptor 2 (CCL2/CCR2) signaling pathway in electroacupuncture (EA)-induced reduction of spinal cord injury (SCI) in rats.Methods:Sixty clean-grade healthy adult female Sprague-Dawley rats, weighing 210-250 g, were divided into 5 groups ( n=12 each) using a random number table method: sham operation group (group S), group SCI, SCI+ Anti-CCL2 group (group SCI+ A), SCI+ EA group (group SCI+ EA), and spinal cord injury+ EA+ rCCL2 group (group SCI+ EA+ R). The SCI model was established using the Allen method in anesthetized animals. Group S only underwent spinous process and laminectomy without damaging the spinal cord. In SCI+ A group, CCL2 neutralizing antibody 50 μg/kg was intrathecally injected at 0, 3 and 6 days after successful development of the SCI model. On the 7th day after the successful development of the SCI model, Jiaji, Dazhui and Mingmen acupoints were stimulated with a depth of 2 mm, voltage of 12-15 mV and frequency of 2 Hz for 30 min once a day for 7 consecutive days in SCI+ EA group. In SCI+ EA+ R group, recombinant rat CCL2 2.5 μg/kg was intrathecally injected at the site of injury at 0, 3 and 6 days after successful development of the SCI model, and the remaining treatments were similar to those in SCI+ EA group. At 1 day before developing the model, 0, 3, 7, 14, 21 and 28 days after developing the model, the mechanical paw withdraw threshold (MWT) and thermal paw withdrawal latency (TWL) were measured, and the motor function was assessed by BBB score. The rats were sacrificed after the final behavioral testing, and their spinal cord tissues were obtained for determination of the expression of CCL2 and CCR2 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction), the expression of GFAP (by immunofluorescence), contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay) and for examination of the pathological changes (using HE staining). Results:Compared with S group, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI group ( P<0.05). Compared with SCI group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 7 days after developing the model in SCI+ A group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 14 days after developing the model in SCI+ EA group, and the expression of CCL2 and CCR2 protein and mRNA and GFAP was significantly down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in SCI+ A and SCI+ EA groups ( P<0.05). Compared with SCI+ EA group, the MWT and BBB scores were significantly decreased at 14 days after developing the model, the TWL was shortened, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI+ EA+ R group ( P<0.05). Compared with SCI+ A and SCI+ EA groups, the histopathological injury were significantly attenuated in SCI group, and the histopathological injury was aggravated in SCI+ EA+ R group. Conclusions:The CCL2/CCR2 signaling pathway is involved in the process by which EA reduces SCI, and the mechanism is related to the inhibition of astrocyte activation, thereby reducing the inflammatory response.

AIM To investigate the ameliorative effects of Compound Fufangteng Mixture(CFM)on cyclophosphamide(CTX)-induced immunosuppression in mice.METHODS Forty-eight male C57BL/6J mice were randomly divided into the blank control group,the model group,the levamisole hydrochloride group(40 mg/kg)and the low-dose,medium-dose and high-dose CFM groups(3.75,7.5,10 g/kg),with 8 mice in each group,and given respective intervention orally once daily for 14 days.On the 5th to 7th day of administration,with the blank control group given normal saline intraperitoneally,the other groups underwent intraperitoneal CTX injections(80 mg/kg).24 hours after the last administration,organ indices of thymus and spleen were calculated;splenic histopathological alterations were assessed by HE staining;serum levels of IL-2,IL-6 and IgG were quantified using ELISA;splenic CD4+,CD8+T lymphocytes,alongside CD86+and CD206+macrophages populations were analyzed by flow cytometry;and splenic expression of CD4,CD8 and F4/80 was evaluated by immunohistochemical staining.RESULTS In CTX-treated mice,CFM administration mitigated body weight loss;enhanced thymus weight and thymic index;ameliorated splenic immune cell populations,elevated serum levels of cytokines IL-2,IL-6 and IgG in serum;and upregulated splenic levels of CD45+CD3+T lymphocytes and F4/80+CD11b+macrophages,alongside increasing the expression of CD4,CD8 and F4/80 surface markers.CONCLUSION CFM alleviates CTX-induced immunosuppression state in mice by modulating immune cells,restoring immune function and enhancing anti-inflammatory and tissue repair capabilities.

Objective:To investigate the longitudinal stability of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Activity of Daily Living Scale (ADL).Methods:The longitudinal cognitive assessment results of 68 dementia patients admitted to the Dementia and Leukoencephalopathy Outpatient Clinic, Department of Neurology, Peking Union Medical College Hospital, from January 2021 to January 2024, were retrospectively analyzed, including the total and sub-items scores of the MMSE, MoCA, and ADL. Two different rules were applied to analyze the abnormality rates: rule 1, where the current test result being better than the previous one was considered an abnormality; rule 2, where the current test result being better than the previous average score was considered an abnormality (If a patient had only 2 cognitive assessments, rule 2 was considered the same as rule 1). Two rules were used to analyze the abnormality rates of the scales. The statistical analyses were repeated after excluding patients with possible anxiety and depression status.Results:In assessing the total score stability, MMSE showed the lowest abnormality rates [27.2% (31/114) under rule 1 and 29.8% (34/114) under rule 2], while MoCA had the highest abnormality rates [41.3% (26/63) and 46.0% (29/63), respectively]. The ADL abnormality rates were 27.7% (23/83) and 33.7% (28/83), respectively. Among MoCA sub-items, category cue, multiple choice cue, second memory trial, orientation, and clock showed higher abnormality rates [31.7%(20/63), 30.2%(19/63), 23.8%(15/63), 22.2%(14/63), 22.2%(14/63), respectively]. After excluding population with possible anxiety and depression status, the relative abnormality rates of MMSE and ADL sub-items did not significantly change, while the abnormality rate of orientation in MoCA sub-items decreased relatively.Conclusion:The MMSE and ADL exhibit good stability in long-term monitoring of dementia patients, serving as essential tools for assessing and following up cognitive changes.

Objective:To understand the etiological surveillance and drug resistance characteristics of Legionella pneumophila (LP) from the aqueous environment of public places in Shanghai, from 2011 to 2020, and provide evidence for surveillance of the disease. Methods:Environmental water samples were systematically collected from public venues in urban and suburban districts of Shanghai for LP surveillance. All the identified LP isolates underwent a series of testings including serotyping, pulsed field gel electrophoresis (PFGE), sequence-based typing, and antimicrobial susceptibility testing. χ2 test or Cochran-Armitage trend tests were used for statistical analysis and for temporal resistance patterns. Results:Among 6 263 water samples, the LP-positive rate was 20.93% (1 311/6 263). The positivity rate decreased from 24.98% (287/1 149) in 2011-2012 to 20.02% (1 024/5 114) in 2013-2020 ( χ2=13.92, P<0.001), with the highest monthly positivity observed from June to August (23.79%, 745/3 132). A total of 1 365 LP strains were isolated, of which 912 were further characterized, including 10 serotypes, 149 PFGE patterns, and 33 sequence types (ST). The predominant serotype was Lp1 (86.84%, 792/912), and the dominant ST was ST752 (29.50%, 269/912). ST clustering revealed two major clonal groups CG1 and CG2, accounting for 91.12% (831/912) of the isolates. The 190 LPs involved in the drug sensitivity test showed three resistance profiles: azithromycin resistance (31.05%, 59/190), ciprofloxacin resistance (0.53%, 1/190) and azithromycin+ciprofloxacin resistance (0.53%, 1/190). Azithromycin-resistant strains were predominantly ST1 (64.41%, 38/59). The antimicrobial resistance rate showed a significant decline, from 48.65% (18/37) in 2011-2012 to 28.10% (43/153) in 2013-2020 ( χ2=9.38, P=0.002). Conclusions:Compared to from 2011 to 2012, both the positivity rate and antimicrobial resistance prevalence of LP in public aqueous environments of Shanghai exhibited an overall decline from 2013 to 2020. The predominant types of LP were serotype Lp1 and sequence type ST752, with notable high-level resistance to azithromycin. Measures as enhancing the enforcement of water safety regulations and prioritizing surveillance of azithromycin resistance in LP were recommended to mitigate public health risks.