Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

ObjectiveTo analyze the characteristics of 150 patients with spinal cord injury complicated with spasticity. MethodsA cross-sectional survey was conducted on 150 patients with spinal cord injury accompanied by spasticity from September, 2019 to December, 2024. Their age, gender, cause of injury, injury site, severity of injury, spasticity severity and other indicators were recorded. The relationships between different characteristics were analyzed, and a correlation analysis of disease duration, spasticity grade, injury level, injury severity and age were conducted. ResultsThere was no significant difference in age distribution between patients with tetraplegia and paraplegia (Z = 0.806, P = 0.420). The proportions of trauma (χ² = 3.982, P = 0.046) and tetraplegia (χ² = 10.559, P = 0.010) were higher in males than in females. Trauma was the main cause of injury in both tetraplegia and paraplegia patients; the proportion of tetraplegia was higher than paraplegia in trauma patients, while paraplegia was higher than tetraplegia in non-trauma patients (χ² = 11.885, P < 0.001). Patients with tetraplegia was dominated by incomplete injury, whereas patients with paraplegia was dominated by complete injury (χ² = 10.885, P = 0.012). Grade A injury was predominant in trauma patients (P = 0.003). Spasticity grade showed a very weak positive correlation with disease duration (r = 0.175, P = 0.032) and age (r = 0.168, P = 0.040). Injury severity showed a very weak positive correlation with age (r = 0.183, P = 0.025). ConclusionCharacteristics of patients with spinal cord injury complicated with spasticity is different with gender, cause of injury, injury level, injury severity.

ObjectiveTo explore the incidence of major low anterior resection syndrome （LARS） within six months after sphincter-preserving surgery for rectal cancer and to analyze its associated factors. MethodsClinical records， postoperative rehabilitation data and LARS scores were collected from 889 patients at 3 months postoperatively and from 844 patients at 6 months postoperatively. Patients were divided into a major LARS group and a non-major LARS group. Multivariable Logistic regression was used to analyze factors associated with major LARS at 3 and 6 months postoperatively， and the predictive value of the models was assessed using the Hosmer-Lemeshow goodness-of-fit test and the receiver operating characteristic （ROC）. ResultsAmong patients undergoing sphincter-preserving surgery for rectal cancer， 247 patients （27.8%） had major LARS at 3 months postoperatively and 181 patients （21.4%） at 6 months postoperatively. Multivariable Logistic regression showed that Kegel exercises， preoperative radiotherapy， anastomotic leakage， a tumor distance from the anal verge of ≤5 cm， and an anastomotic distance from the anal verge of ≤5 cm were independent factors for major LARS at 3 months postoperatively （P<0.05）. At 6 months postoperatively， occasional Kegel exercises during 0~3 months， Kegel exercises during 4~6 months， hydrotherapy during 4~6 months， preoperative chemotherapy， a tumor distance from the anal verge of ≤5 cm， and an anastomotic distance from the anal verge of ≤5 cm were independent factors （P<0.05）. The models at 3 and 6 months postoperatively showed goodness-of-fit test P values of 0.986 and 0.517 and area under the curve （AUCs） of 0.843 and 0.870， indicating good predictive value. ConclusionThe incidence of major LARS within six months after sphincter-preserving surgery for rectal cancer is relatively high， and greater attention should be paid to patients who receive preoperative chemoradiotherapy， develop anastomotic leakage， or have tumor and anastomotic distances from the anal verge of ≤5 cm. Patients should also be advised that early postoperative Kegel exercises and hydrotherapy may reduce the incidence of major LARS.

OBJECTIVE T o assess the in vitro antimicrobial activity of aztreonam-avibactam against metallo-β—lacta-mase(MBL)-producing carbapenem-resistant Enterobacteriaceae(CRE)using different antimicrobial susceptibility testing methods,evaluate the consistency of results based on the latest breakpoints recommended by European Committee on Antimicrobial Susceptibility Testing(EUCAST),and analyze the clinical applicability.METHODS The imipenem-or meropenem-resistant Enterobacteriaceae strains were isolated from the clinical specimens of Bei-jing Chaoyang Hospital from Jan.2019 to Mar.2023,MBL-producing CRE were selected after they were con-firmed by colloidal gold immunoassay and Sanger sequencing as the study subjects.The minimum inhibitory con-centrations(MICs)of single aztreonam and aztreonam-avibactam compounds were determined by using broth mi-crodilution method.In addition,the disk diffusion method and the gradient diffusion method were employed to further detect the in vitro susceptibility to aztreonam-avibactam.RESULTS Among the 87 strains of MBL-producing CRE that were included in the study,Escherichia coli was the most common species,accounting for 44.83％.NDM-5 was the predominant carbapenemase type,detected in 48.28％of the isolates.According to the latest EUCAST break-points,6 isolates were aztreonam-avibactam-resistant strains based on broth microdilution method,all of which were E.coli,and the resistance rate was 6.90％(6/87).However,the resistance rate that was determined by the disk diffu-sion method was significantly higher(22.99％,20/87).Among these,14 strains was within the area of technical uncer-tainty/resistant,making result interpretation difficult.In addition,the categorical agreement between the gradient diffu-sion method and the broth microdilution method reached up to 98.85％.CONCLUSIONS Aztreonam-avibactam has high antimicrobial activity against MBL-producing CRE.However,based on the latest EUCAST breakpoints,the antimicrobial susceptibility testing by the disk diffusion method results of some strains are hard to interpret.It is necessary to integrate with other methods for further validation.

OBJECTIVES: This study aimed to investigate the perception of dental outpatient care quality from multiple perspectives of administrators, physicians, nurses, and patients and propose nursing care quality evaluation indices that are consistent with the clinical reality to provide reference for the construction of a scientific, systematic, and comprehensive dental outpatient care quality evaluation system. METHODS: A total of 39 interviewees, including 7 administrators, 11 doctors, 11 nurses, and 10 patients, were selected for semi-structured in-depth interviews in five regionally representative tertiary-level A stomatological specialty hospitals nationwide during January-April 2024 by using a multistage sampling method. Colaizzi 7-step analysis was used to analyze and summarize the interview data. Themes were extracted on the basis of the Structure-Process-Outcome (SPO) three-dimensional quality assessment model. RESULTS: Five main themes and 15 secondary themes were extracted from three quality dimensions: structure, process, and result. The related topics of structural quality were as follows: disinfection and isolation norms, equipment and consumable management, nursing manpower ratio and nurse education structure, and emergency capability. The related topics of process quality were as follows: pre-diagnosis risk assessment, patient triage and guidance, communication and attitude, health education, humanistic care, continuous care, specialty operation, and four-hand operation. The related topics of result quality were as follows: satisfaction, adverse event management and analysis, effective complaints and disputes. CONCLUSIONS Structure quality is the foundation, process quality is the core, and result quality is the key in the evaluation of the quality of oral outpatient care. The standardization of disinfection and isolation, equipment and consumable management, allocation of reasonable nursing manpower and post capacity, implementation of high-quality nursing services, and improvement of the quality and satisfaction of medical cooperation are necessary guarantees to ensure the quality of oral outpatient care.
Humans ; Quality of Health Care ; Ambulatory Care/standards* ; Dental Care/standards* ; Outpatients

Objective:To analyze the epidemiological characteristics of drug resistance genes of carbapenemase-producing Escherichia coli (CPECO) in Henan Province Hospital of Traditional Chinese Medicine from 2021 to 2023, providing data support and theoretical basis for controlling nosocomial infections of CPECO.Methods:Using a cross-sectional study, 30 carbapenem-resistant Escherichia coli (CRECO) strains confirmed by VITEK-2 Compact identification and drug sensitivity test in the Clinical Microbiology Laboratory of Henan Province Hospital of Traditional Chinese Medicine from 2021 to 2023 were tested, using carbapenemase inhibitor enhancement test to conduct preliminary screening of carbapenemases, and colloidal gold immunochromatography and polymerase chain reaction (PCR) were used to determine the phenotypes and genotypes of common carbapenemases ( blaKPC, blaNDM, blaVIM, blaIMP, blaOXA) respectively, and the genotypes ( blaSHV, blaTEM, blaCTX) of common extended Spectrum beta-lactamases (ESBL) were confirmed using PCR. The PCR amplification products of carbapenemase and ESBL positive strains were Sanger-sequenced, and the sequencing products were compared on the Blast website to determine the exact carbapenemase and ESBL genotypes. Sequence typing (ST) was performed on CPECO using the Achtman multi-locus sequence typing scheme to determine the cloning relationship between different strains. Results:A total of 21 CPECO strains were screened. Drug sensitivity test results showed that CPECO strains showed widespread drug resistance, with the resistance rate to monocyclic (aztreonam) and trimethoprim/sulfamethoxazole being over 60%(16/21, 14/21), and the resistance rate to other antibacterial drugs being 100%. Only the sensitivity to aminoglycosides and fosfomycin remained relatively high, and no strains resistant to tigecycline and colistin were found. Colloidal gold immunochromatography detected 18 blaNDM types, 2 blaKPC types, and 1 blaIMP type. Sequencing of drug resistance gene PCR products classified 17 blaNDM-5 strains, 1 blaNDM-4 strain, 2 blaKPC-2 strain, and 1 blaIMP-4 strain, which were completely consistent with the results of screening test and colloidal gold immunochromatography. ESBL resistance gene testing showed that the detection rate of blaTEM was 42.9%(9/21), blaCTX-M was 33.3%(7/21), and blaSHV was 4.8%(1/21). The rate of blaNDM producing CPECO carrying both ESBL resistance genes was 27.8%(5/18). The MLST typing results revealed 11 sequence types (STs), including one ST155 clonal complex and nine singleton STs. Among these, there were seven strains of ST167, five strains of ST410, and one strain each of ST58, ST68, ST69, ST93, ST131, ST155, ST648, ST1114, and ST3268. Conclusion:The main resistance mechanism identified in this study for CPECO was the production of blaNDM-5 carbapenemase, with a high proportion of strains also carrying blaTEM-1D and/or blaCTX-M-15 ESBLs. MLST typing found that the epidemic strain of CPECO showed certain polymorphism, but there were clonal transmission of multiple clonal complexes between ST167 and ST410.

Objective:To investigate the effect of Yiqi Shengqing Formula on neuronal damage in ischemic stroke(IS)rats by regulating brain-derived neurotrophic factor(BDNF)-extracellular regulated protein kinase(ERK)-cyclic adenosine monophosphate-responsive element binding protein(CREB)signal pathway.Methods:IS rat model was prepared by modified thread suppository method,and randomly divided into model group,low dose Yiqi Shengqing Formula(3 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)+empty load group,high dose Yiqi Shengqing Formula(6 g/kg)+BDNF knockdown group,with 10 rats in each group,another 10 healthy rats were set as sham operation group.After intervention with Yiqi Shengqing Formula and plasmid,neural function of rats in each group was scored with Longa scoring method;Morris water maze test was used to detect cognitive impairment of rats in each group;Nissl staining was used to detect the number of neurons in ischemic peripheral brain tissue and hippocampus of rats in each group;synaptic morphology of ischemic peripheral brain tissue was detected by silver staining;levels of TNF-α and IL-8 in brain tissue and serum of rats in each group were measured by ELISA;expressions of BDNF-ERK-CREB signal pathway related proteins in rat brain were detected by Western blot.Results:Compared with sham operation group,synaptic morphology of ischemic peripheral brain tissue in model group was severely damaged,retention time in target quad-rant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased significantly(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased significantly(P<0.05).Compared with model group,synaptic morphological damage of ischemic peripheral brain tissue in rats in low dose Yiqi Shengqing Formula group and high dose Yiqi Shengqing Formula group was alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were decreased(P<0.05).Compared with low dose Yiqi Shengqing Formula group,damage of synaptic morphology in ischemic peripheral brain tissue of rats in high dose Yiqi Shengqing Formula group was further alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were further increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were further reduced(P<0.05).Compared with high dose Yiqi Shengqing Formula group,synaptic morphological damage of ischemic peripheral brain tissue in high dose Yiqi Shengqing Formula+BDNF knockdown group was aggravated,retention time in target quadrant,times of crossing the platform,number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased(P<0.05);there was no significant changes in each index of rats in high dose Yiqi Shengqing Formula+empty load group(P>0.05).Conclusion:Yiqi Shengqing Formula can inhibit the neuroinflammation of IS rats by activating BDNF-ERK-CREB signal,thereby reducing the damage of its neurons and improving its neural function.

OBJECTIVE T o assess the in vitro antimicrobial activity of aztreonam-avibactam against metallo-β—lacta-mase(MBL)-producing carbapenem-resistant Enterobacteriaceae(CRE)using different antimicrobial susceptibility testing methods,evaluate the consistency of results based on the latest breakpoints recommended by European Committee on Antimicrobial Susceptibility Testing(EUCAST),and analyze the clinical applicability.METHODS The imipenem-or meropenem-resistant Enterobacteriaceae strains were isolated from the clinical specimens of Bei-jing Chaoyang Hospital from Jan.2019 to Mar.2023,MBL-producing CRE were selected after they were con-firmed by colloidal gold immunoassay and Sanger sequencing as the study subjects.The minimum inhibitory con-centrations(MICs)of single aztreonam and aztreonam-avibactam compounds were determined by using broth mi-crodilution method.In addition,the disk diffusion method and the gradient diffusion method were employed to further detect the in vitro susceptibility to aztreonam-avibactam.RESULTS Among the 87 strains of MBL-producing CRE that were included in the study,Escherichia coli was the most common species,accounting for 44.83％.NDM-5 was the predominant carbapenemase type,detected in 48.28％of the isolates.According to the latest EUCAST break-points,6 isolates were aztreonam-avibactam-resistant strains based on broth microdilution method,all of which were E.coli,and the resistance rate was 6.90％(6/87).However,the resistance rate that was determined by the disk diffu-sion method was significantly higher(22.99％,20/87).Among these,14 strains was within the area of technical uncer-tainty/resistant,making result interpretation difficult.In addition,the categorical agreement between the gradient diffu-sion method and the broth microdilution method reached up to 98.85％.CONCLUSIONS Aztreonam-avibactam has high antimicrobial activity against MBL-producing CRE.However,based on the latest EUCAST breakpoints,the antimicrobial susceptibility testing by the disk diffusion method results of some strains are hard to interpret.It is necessary to integrate with other methods for further validation.

Very-late-onset schizophrenia-like psychosis(VLOSLP)is considered the most common mental disorder in the elderly following dementia and depression, and its clinical symptomatology is different from that of schizophrenia with onset around the average age.The diagnostic classification system and prognosis of VLOSLP are very complicated, and it is still controversial whether it should be classified as a prodromal symptom of dementia or as a type of late-onset schizophrenia.This article reviewed studies concerning the epidemiology, clinical features, diagnosis, prognosis, and neuroimaging of VLOSLP, hoping to provide value as a reference for future clinical research and treatment.