ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

A case report of adult skeletal class Ⅲ patient with high angle open bite is presented in this article.The patient underwent extraction of bilateral mandibular first molars and straightening the third molars,open bite was resolved,normal over bite,over jet and good occlusion were established.

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree with recurrent Joubert syndrome with negative results by whole-exome sequencing in the prior proband. METHODS: Chinese pedigree which opted elective abortion at the Women and Children's Hospital Affiliated to Chongqing Medical University in December 2024 was selected as the study subject. Whole-genome sequencing was carried out on fetal tissue after termination of pregnancy. Candidate variants were validated by Sanger sequencing and interpreted, while non-coding variant was analyzed using in silico prediction tools. RNA sequencing and cDNA sequencing were conducted on fetal brain tissue. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.2024YL045-02). RESULTS: Both the fetus and the affected child were found to harbor compound heterozygous variants of the CEP290 gene, namely c.7341dup (p.Leu2448fs*8) (pathogenic, maternally inherited) and c.1523-408G>A (likely pathogenic, paternally inherited). Both in silico analysis and fetal brain RNA sequencing confirmed aberrant RNA splicing caused by the intronic variant. CONCLUSION This case has highlighted the value of combining whole-genome sequencing with RNA functional validation. Above results not only enriched the spectrum of CEP290 gene mutations but also underscored its diagnostic value in resolving complex prenatal cases, providing critical clues for the prenatal diagnosis and recurrence risk assessment in genetic counseling.
Female ; Humans ; Pregnancy ; Abnormalities, Multiple/genetics* ; Antigens, Neoplasm/genetics* ; Cell Cycle Proteins/genetics* ; Cerebellum/abnormalities* ; Cytoskeletal Proteins/genetics* ; Eye Abnormalities/genetics* ; Introns/genetics* ; Kidney Diseases, Cystic/diagnosis* ; Pedigree ; Retina/abnormalities* ; Sequence Analysis, RNA/methods* ; Whole Genome Sequencing/methods* ; Child

Objective:To explore the influence of management mode of Deming cycle(plan,do,check,action,PDCA)combined with 6S management method on management effect of medical equipment in orthopedic department,and to improve the management quality for medical equipment in orthopedic department.Methods:In accordance with the combination of four stages of PDCA management and the six links(organization,tidying,cleaning,cleanliness,literacy and safety)of 6S management method,the medical equipment of orthopedic department was managed as stage by stage and link by link.Twelve using medical equipment in the orthopedic department of the Second Affiliated Hospital of Air Force Military Medical University were selected between 2022 and 2023.The management level between conventional management and management mode after the management mode of PDCA combined with 6S management mothed was implemented was compared,and the equipment fault and adverse event between within 87361 h before the management mode was used and within 87054 h after the management mode was used also were compared.The scores of satisfaction ratings of 15 medical staffs who involved in using equipment were investigated by using self-made questionnaire.Results:The scores of training assessment,regular maintenance,daily inspection,regular quality control and standardized use,and the total scores after used management mode of PDCA combined with 6S management method were respectively(18.87±0.66),(18.25±0.73),(18.74±0.69),(18.36±0.64),(18.89±0.54)and(92.11±4.20),all of which were higher than those before the management mode was implemented,and the differences of them were statistically significant(t=5.047,3.301,3.396,3.191,3.107,6.170,P<0.05).The standby time due to equipment fault and fault rate within 87054 h of using equipment after the management mode was implemented were respectively 262h and 0.30%,all of which were lower than those before the management mode was implemented,and the differences of them were statistically significant(x2=52.876,P<0.05).The incidence of adverse events of 12 equipment was 0.00%after the management mode was implemented,which was lower than that before it was implemented,and the difference was statistically significant(x2=4.800,P<0.05).The scores of 15 medical staffs on the performance,cleanliness,maintenance,consuming and technical support of equipment,and the total scores were respectively(18.41±1.11),(18.35±1.05),(18.58±0.87),(18.26±1.00),(18.77±0.89)and(92.21±4.12)scores after the management mode was implemented,which were higher than those before it was implemented,and the differences were statistically significant(t=5.257,4.939,5.429,3.191,4.705,9.858,P<0.05).Conclusion:The application of the management mode of PDCA combined with 6S management method in medical equipment management of orthopedic department can improve the management level for equipment,and reduce the incidences of equipment fault and adverse events in using equipment,and improve the satisfaction of medical staffs in using equipment.

Objective To investigate the effects and mechanisms of Huatan Quyu Decoction on learning and memory abilities in rats with vascular dementia(VD).Methods Totally 112 male SD rats were randomly selected with 16 rats as the sham-operation group,the remaining rats were used to prepare VD models by segmental ligation of the common carotid artery.The successfully modeled rats were randomly divided into model group,Huatan Quyu Decoction low-,medium-and high-dosage groups(6.1,12.1,24.2 g/kg),donepezil hydrochloride group(0.5 mg/kg)and combination group(Huatan Quyu Decoction 12.1 g/kg+donepezil hydrochloride 0.5 mg/kg),with 16 rats in each group.Each group was given the corresponding treatment measures for 4 weeks.The Morris water maze test was used to assess learning and memory abilities,neurological function was evaluated using Garcia score,HE staining was used to observe the morphology of the hippocampal tissue,ELISA was employed to detect the serum content of Aβ,immunohistochemistry was utilized to observe the β-catenin,LRP6 and GSK-3β protein expression in brain tissue.Results Compared with the sham-operation group,the escape latency of the model group rats was prolonged(P<0.01),the number of crossing platforms was reduced(P<0.01),and the neurological deficit score was decreased(P<0.01),the arrangement of hippocampal tissue cells was disorderly,and the tissue was severely damaged,the serum Aβ content increased(P<0.01),the expressions of β-catenin and LRP6 protein in brain tissue decreased,and the expression of GSK-3β protein increased(P<0.01).Compared with the model group,the escape latency of rats in each administration group was shortened,the number of crossing platforms increased,the neurological deficit score increased,the number of hippocampal cells was relatively more,the arrangement was more orderly,and the structure was relatively complete,the serum Aβ content decreased,the expressions of β-catenin and LRP6 proteins increased,and the expression of GSK-3β protein decreased.Among them,Huatan Quyu Decoction high-dosage group had a significantly better effect than Huatan Quyu Decoction low-and medium-dosage groups(P<0.01),and there was no statistical significance in various indicators compared with the donepezil hydrochloride group(P>0.05).Compared with the donepezil hydrochloride group,the combination group showed significant improvements in learning and memory abilities(P<0.01),the neurological deficit score significantly increased(P<0.01),the number of hippocampal cells significantly increased,arranged neatly,and structurally intact,the serum Aβ content significantly decreased(P<0.01),the expression of β-catenin and LRP6 proteins significantly increased,and the expression of GSK-3β protein significantly decreased(P<0.01).Conclusion Huatan Quyu Decoction can repair cognitive function in VD rats,improve learning and memory abilities,and alleviate VD symptoms by activating the Wnt/β-catenin signaling pathway to reduce serum Aβ content,decrease the apoptosis of nerve cells and alleviate the degree of pathological damage in hippocampal tissue.

In the pathological process of acute lung injury,uncontrolled inflammatory response will lead to severe consequences,and pyroptosis plays a vital factor in a cell programmed inflammatory necrosis.When the body is imbalanced due to excessive pyroptosis,it can lead to lung injury in the lungs.TCM emphasizes the balance of the body and the balance of yin and yang.Based on the"yin-yang"theory and"pathogenic factors and healthy qi"theory of TCM,this article discussed the yin-yang changes,growth and decline,and opposing constraints of cell pyroptosis in the occurrence and development of acute lung injury at the cellular level,and explained the possible basis of TCM in preventing and treating cell pyroptosis,providing theoretical reference for the intervention of TCM in the prevention and treatment of acute lung injury with cell pyroptosis.

Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.

OBJECTIVE To explore the clinical value of metagenomic next generation sequencing(mNGS)in detec-tion of pathogens from the patients with pulmonary infection.METHODS The clinical data were collected from 103 patients with pulmonary infection who were treated in respiratory and critical care medicine department of Gansu Province People's Hospital from Jun.2021 to Jun.2023.The pathogens were detected from all of the patients with the use of mNGS for bronchoalveolar lavage fluid(BALF)and traditional cultures(including sputum culture and BALF culture).The positive rates,consistency,distribution,efficacy and curative effects were observed and sys-tematically compared between the two detection methods.RESULTS Totally 122 strains of bacteria,47 strains of fungi,94 strains of viruses,3 strains of Mycoplasma and 2 strains of Chlamydia were detected from the 103 pa-tients by mNGS,as compared with only 45 strains of bacteria and 20 strains of fungi that were detected by the tra-ditional culture method.The positive rate of detection of pathogens was 89.32％by mNGS,higher than 38.83％of the traditional culture method(P＜0.001).There was certain difference in the distribution of pathogens be-tween the two detection method,the two detection method showed the poor consistency of detection efficacy,and the effect of targeted drug therapy based on the mNGS-detected pathogens was higher than that of the mNGS-negative empirical therapy(P＜0.001).In addition,some of drug resistance genes could be detected by mNGS.CONCLUSIONS The mNGS shows remarkable higher efficacy in detection of the pathogens causing pul-monary infections than the traditional culture method and can detect various types of pathogens.The effect of the targeted drug therapy based on the pathogens detected by mNGS is remarkable.It plays an imorptant role in guid-ing the clinical diagnosis and treatment of the patients with pulmonary infections.

Objective To investigate the inhibitory effect of Scutellaria baicalensis combined with 5-Fu on Lewis tumor bearing mouse lung cancer based on the JAK2/STAT3 signaling pathway.Methods To detect the changes in body mass,food intake and tumor volume of Lewis tumor-bearing mice after intervention of Scutellaria baicalensis(20 mg/kg)combined with 5-Fu.Pathological changes in tumor tissue were observed by HE staining,expression levels of proliferation related protein Ki67 were observed by immunohistochemical staining,changes in cell apoptosis levels in tumor tissue were observed by TUNEL staining,and changes in expression levels of JAK2,p-JAK2,STAT3,and p-STAT3 proteins in tumor tissue were observed by immunohistochemical staining.Results Compared with the model group,the tumor volume of mice after combined intervention significantly decreased(P＜0.01)and body mass increased(P＜0.05),but there was no significant change food intake.The expression of proliferation related protein Ki67 in tumor tissue was significantly reduced,and the number of apoptotic cells labeled with TUNEL was significantly increased;The expression of p-JAK2 and p-STAT3 proteins is elevated.Conclusions Scutellaria baicalensis decoction can inhibit the JAK2/STAT3 signaling pathway and increase the inhibitory effect of 5-Fu on mouse lung cancer.

Objective:To explore the risk factors of quality of life(QoL)being below normal levels in patients undergo-ing total knee arthroplasty(TKA)at 6 months after surgery,and to construct a nomogram prediction model.Method:Two-hundred and sixty-seven patients who underwent TKA at Qingdao Hospital,University of Health and Rehabilitation Sciences(Qingdao Municipal Hospital)from April 2021 to October 2022 were selected.Clini-cal data were collected on admission and within 6 months after surgery.According to the QoL assessment at 6 months after surgery,they were divided into a high-quality group(n=136)and a non-high-quality group(n=131).LASSO regression was used to screen the predictors,and multivariate Logistic regression was established to construct the predictive model of QoL of TKA patients at 6 months after surgery.Receiver operating character-istic curve(ROC curve),calibration curve and decision curve were drawn to evaluate its predictive value.Result:A total of 131(49.06%)patients had lower QoL than normal 6 months after TKA.LASSO regression selected age,surgical side,education level,duration of knee osteoarthritis(KOA),perioperative recovery,and visual analog scale(VAS)during preoperative rest as predictors.Multivariate logistic regression analysis showed that age(OR,1.08;95%CI,1.01-1.15),duration of KOA(OR,1.13;95%CI,1.05-1.22),VAS during preoperative rest(OR,1.94;95%CI,1.20-3.15),and perioperative rehabilitation(OR,0.42;95%CI,0.18-0.97)were independent risk factors for lower than normal QoL in TKA patients at 6 months after surgery(P<0.05).Statistically significant indicators in multivariate logistic regression analysis were includ-ed in the nomogram model,which underwent internal validation.The area under the ROC curve was 0.829(95%CI,0.779-0.879),indicating good predictive ability of the model.The calibration curve showed good consistency between the predicted probability and the actual probability.The decision curve analysis showed that this model is clinically applicable.Conclusion:Age,duration of KOA,VAS during preoperative rest,and perioperative rehabilitation are indepen-dent predictors of lower-than-normal QoL in TKA patients at 6 months after surgery,and the nomogram mod-el based on the above indicators had good predictive performance.