[Objective] To explore the predictive value of HALP score for prognosis in patients with multiple myeloma (MM). [Methods] A retrospective analysis was conducted on laboratory indicators and related clinical data of newly diagnosed multiple myeloma (NDMM) patients, treated at the Affiliated Hospital of North Sichuan Medical College from January 2016 to October 2023, prior to their first treatment. The HALP score was calculated, and the optimal cutoff value for HALP was determined using X-tile software. Survival analysis was performed using Kaplan-Meier curves for high HALP and low HALP groups. Univariate and multivariate analyses were conducted using the Cox regression model, and a forest plot was generated using Graphpad Prism to illustrate factors that may impact patient prognosis. The predictive ability of HALP score combined with β2-microglobulin and ECOG score for prognosis in MM patients was evaluated using receiver operating characteristic curve (ROC) analysis. [Results] A total of 203 MM patients were included, with the optimal cutoff value for HALP score being 29.15 (P<0.05). Among them, 101 patients were in the low HALP score group, and 102 patients were in the high HALP score group. The results of univariate and multivariate analysis using the Cox regression model showed that a HALP score <29.15 was an independent risk factor for progression-free survival (PFS) and overall survival (OS) (P<0.05). ROC curve analysis indicated that the combination of HALP score with β2-microglobulin and ECOG score had a higher predictive value for prognosis in MM patients compared to using HALP score alone. [Conclusion] The HALP score is closely related to the prognosis of patients with NDMM. A low HALP score indicates a poorer prognosis, while the combination of HALP score with β2-microglobulin and ECOG score provides a higher predictive value when assessed together.

Background A diverse cohort of patients and susceptible individuals congregate in healthcare facilities, where exposure to pathogenic microorganisms associated with respiratory infectious diseases constitutes a significant risk factor for cross-infection. Central air-conditioning ventilation systems improve some indoor environment indicators while exacerbating the risk of transmission of respiratory infectious diseases. Objective To investigate the distribution characteristics of microbial communities in the central air-conditioning ventilation systems of hospitals, providing a scientific basis for the selection of microbial indicators in hygiene standards for hospital central air-conditioning ventilation systems and for hospital risk early warning systems. Methods In October 2023, two central air-conditioning ventilation systems were selected from a Grade 3A hospital in Shanghai: one was an all-air air-conditioning system serving the waiting area on the ground floor, and the other was a fan coil plus fresh air system serving the outpatient area on the third floor. Samples from four different components of the ventilation systems—air outlets, filters, surface coolers, and condensate trays—were collected for high-throughput sequencing of the 16S rRNA gene to analyze bacterial communities. Alpha-diversity and beta-diversity analyses were performed to investigate the microbial community composition and diversity characteristics of the hospital central air-conditioning ventilation systems. Functional analysis was conducted to determine the relative abundance of bacterial functions in these systems.Results A total of 528 operational taxonomic units (OTUs) were identified, encompassing 20 bacterial phyla, 37 classes, 79 orders, 123 families, and 240 genera. The analysis revealed that the bacterial community was predominantly composed of Proteobacteria, Gemmatimonadates, Bacteroidetes, and Actinobacteria. The diversity analysis indicated that bacterial community richness and diversity were highest in the condensate trays, while no statistically significant differences (P > 0.05) were observed in the bacterial community composition among the air outlets, filters, and surface coolers. The functional analysis showed that the bacterial communities in the central air-conditioning ventilation systems primarily exhibited chemoheterotrophic, oxidative energy-dependent heterotrophic, and ureolytic functional characteristics. Conclusion The dominance of Proteobacteria suggests that this phylum exhibits strong adaptability in the central air-conditioning ventilation systems, possibly related to its ability to survive and reproduce under varying environmental conditions. The diversity analysis indicates that the condensate tray is a critical area for bacterial proliferation in the central air-conditioning ventilation systems. The similarity in environmental conditions among the air outlets, filters, and surface coolers result in similar bacterial community structures. The functional analysis reveals that the bacterial communities possess robust energy conversion and metabolic capabilities, potentially contributing to processes such as organic matter decomposition and nitrogen cycling within the central air-conditioning ventilation systems.

Objective: To explore the potential application of PAK4-PROTAC targeted degradation drug (PpD) in renal cancer immunotherapy. Methods: TIMER 2.0 and TISIDB databases were used to analyze the relationship among PAK4 expression, tumor purity and abundance of immune cell infiltration in renal tumor microenvironment (TEM).Renal cancer cell lines OS-RC-2, 786-O and ACHN were treated with 0, 125 and 250 nmol/L PpD, and the effects of Jurkat cell co-culture on the results were investigated.The cell apoptosis was detected with flow cytometry, and the expression of programmed cell death 1 ligand 1 (PD-L1) in renal cancer cells was detected with immunoblotting. Results: The high expression of PAK4 was positively related to immune purity, and inhibited the abundance of immune killer cells in TEM, such as CD8 T cells, CD4 T cells, natural killer cells and dendritic cells.With 250 nmol/L PpD treatment, there were 21.02% apoptotic cells in OS-RC-2, 29.67% apoptotic cells in 786-O, and 15.39% apoptotic cells in ACHN, respectively.However, with the same concentration of 250 nmol/L PpD treatment, cell apoptotic rate was sharply increased to 70.13% in OS-RC-2/Jurkat, 70.68% in 780-O/Jurkat, and 60.27% in ACHN/Jurkat co-culture models, respectively. Conclusion: PpD can promote apoptosis of renal cancer cells by reducing the expression of PAK4 protein, and enhance the killing effects of immune cells on tumor cells.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To explore EEG characteristics and the therapeutic effect in children with electrical status epilepticus during slow sleep(ESES).Methods The eligible ESES cases in our center from 2014 to 2020 were included.The age at diagnosis of ESES,the duration of ESES,spike wave index(SWI)during wakefulness and the distribution of spike wave during the period of ESES,age at seizure onset,the clinical syndromes and the outcomes after treatment were analyzed.The ESES cases were divided into 4 groups according to the distribution of spike wave:focal ESES,unilateral ESES,bilateral asymmetric ESES,multiple foci ESES.The SWI during the awake stage were divided into 3 groups based on the different rates:≤20%,21%～49%,≥50%.The therapeutic outcomes were classified into three groups:satisfactory response,seizure control and ineffective.Results 50 cases were included,with 32 males and 18 females.The average onset age of ESES was 6 years and 7 months,and the average duration of ESES was 28 months.A significant correlation between the distribution of ESES and the thera-peutic effects was found,bilateral asymmetric ESES had a good therapeutic effects,while multiple foci ESES showed a poor therapeutic effects.The duration of ESES was significantly correlated with therapeutic effects,and the efficacy was worse when the duration was longer than 1 year.A significant relationship between the SWI during wakefulness of ESES and the therapeutic effects was detected,the patient with SWI≤20%during wakefulness had a good therapeutic effect.There was a negative correlation between the onset age of ESES and the duration of ESES and SWI index during wakefulness.There was a positive correlation between the duration of ESES and SWI index during wakefulness.Conclusion Our results suggest that onset age,distribution,duration and SWI during wake-fulness of ESES were correlated with therapeutic outcomes,The patient with SWI≤20%during wakefulness had a good therapeutic effect and have unfavorable outcomes with ESES last more than 1 year.The earlier onset of ESES,the longer duration of ESES and higher SWI during wakefulness will be showed..

Objective:To investigate the regulatory effect of transient receptor potential cation channel subfamily C member 3 (TRPC3) on the retina in oxygen-induced retinopathy (OIR) mice and biological behavior of human retinal vascular endothelial cells (HREC).Methods:A total of 32 healthy SPF grade 7-day-old C57BL/6 mice were selected and randomly divided into a control group and an OIR group by the random number table method, with 16 mice in each group.The control group received no special treatment, and the OIR model was established in the OIR group.On postnatal day 17 (PN17), the success of the model establishment was verified by immunofluorescence staining of the retinal patch.The in vitro cultured HREC were divided into a normal control group, a transfection reagent group, and a si-TRPC3 group.The normal control group received no special treatment, while the transfection reagent group and the si-TRPC3 group were transfected with transfection reagent or transfection reagent + si-TRPC3.The relative expression of TRPC3 mRNA was detected by real-time quantitative fluorescence PCR.The relative expressions of TRPC3, transcription factor NF-E2 related factor (Nrf2), and superoxide dismutase (SOD) proteins were determined by Western blot.HREC were further divided into a normal control group, a vascular endothelial growth factor (VEGF) group, a si-TRPC3 group, and a Pyr3 (TRPC3 channel inhibitor) group, which were cultured in complete medium, medium containing 20 ng/ml VEGF recombinant protein, medium containing 20 ng/ml VEGF recombinant protein (si-TRPC3 transfection for 72 hours), and medium containing 20 ng/ml VEGF recombinant protein+ 1 μmol/L Pyr3 for 48 hours, respectively.The proliferation ability of HREC was detected using cell counting kit 8 (CCK-8). The horizontal and vertical migration ability of cells were detected by cell scratch assay and transwell assay, respectively.This study followed the 3R principles of animal welfare and was approved by the Ethics Committee of Hebei Eye Hospital (No.2023LW04). Results:Pathological neovascular clusters with strong fluorescent staining appeared in the retina of OIR mice on PN17.The relative expressions of TRPC3 mRNA and protein in the retina of OIR mice were 2.057±0.244 and 1.517±0.290, respectively, significantly higher than 0.983±0.033 and 0.874±0.052 of control group ( t=6.165, 3.094; both at P<0.05). The relative expression levels of TRPC3 mRNA and protein were significantly lower, and the relative expression levels of Nrf2 and SOD proteins were higher in the si-TRPC3 group than in the normal control and transfection reagent groups, and the differences were statistically significant (all at P<0.05). The CCK-8 experiment results showed that the cell absorbance value was higher in the VEGF group than in the normal control group, and lower in the si-TRPC3 and Pyr3 groups than in the VEGF group, with statistically significant differences (all at P<0.05). The results of the cell scratch experiment showed that the lateral migration rate of VEGF group cells was higher than that of normal control group, while the lateral migration rate of si-TRPC3 group and Pyr3 group cells was lower than that of VEGF group, and the differences were statistically significant (all at P<0.05). The transwell experiment results showed that the number of stained cells in the VEGF group was higher than that in the normal control group, and the number of stained cells in the si-TRPC3 group and Pyr3 group was lower than that in the VEGF group, with statistically significant differences (all at P<0.05). Conclusions:Hypoxia induces increased TRPC3 expression in OIR mouse retina, and downregulation of TRPC3 inhibits HREC proliferation and migration.The mechanism is related to the activation of the Nrf2-related oxidative stress pathway.

Objective To investigate the inhibitory effects and mechanisms of α-hederin,an active ingredient in Fruc-tus Akebiae,on hepatocellular carcinoma(HCC)cells.Methods HCC cells were divided into four groups and treated with α-hederin(0,10,20,and 30 μmol·L-1)for 24 h and 48 h,respectively.MTT assays were used to detect the cell proliferation rate,flow cytometry(FCM)was used to detect the apoptotic rate,transcriptomics was used to screen signaling pathways in α-hederin-treated HCC cells,RNA interference was exploited to verify the underlying signaling pathway,and real-time quantitative PCR(qRT-PCR)and Western blotting(WB)were used to detect expression changes of the mRNA and protein of TP53(p53),PMAIP1(Noxa),and apoptosis-associated proteins,Caspase9 and Caspase3.Results α-Hederin induced apoptosis by activa-ting apoptosis-associated proteins,PARP,Caspase9 and Caspase3.Transcriptomics,qRT-PCR,and WB results also showed that α-hederin increased the mRNA and protein expression of p53 and Noxa.Furthermore,α-hederin inhibited the protein degradation of p53 and Noxa,reversing the apoptosis decrease in p53/Noxa siRNA-knocked-down HCC cells.In vivo results showed that α-hederin inhibited the growth of HCC tumors.Conclusion α-hederin may induce the apoptosis of HCC cells by activating and stabilizing the p53/Noxa signaling pathway.

Objective:To explore the correlation between serum levels of interleukin-9 (IL-9), platelet activating factor (PAF), total immunoglobulin E (IgE), interferon γ (IFN-γ), and interleukin-4 (IL-4) in patients with chronic spontaneous urticaria (CSU).Methods:Sixty CSU active phase patients admitted to the First Affiliated Hospital of Hebei North University from March 2018 to March 2019 were selected and included in the CSU active phase group. Based on the 7-day Urticaria Activity Score (UAS7), they were divided into three groups: 15 mild group, 25 moderate group, and 20 severe group; And 19 patients who entered the quiescent phase of the disease after 28 days of standardized antihistamine treatment were included in the CSU quiescent phase group. Another 30 healthy subjects who participated in the physical examination at the same time at our hospital′s physical examination center were selected to be included in the healthy control group. 5 ml of fasting elbow vein blood was collected from CSU active and stationary patients, as well as healthy subjects. The serum levels of IL-9, PAF, total IgE, IFN-γ, and IL-4 were detected using enzyme-linked immunosorbent assay. Pearson correlation test was used to analyze the correlation between serum IL-9, PAF levels and total IgE, IFN-γ, and IL-4 levels in CSU active patients.Results:The serum levels of IL-9, PAF, total IgE, and IL-4 in the CSU active phase group were higher than those in the CSU stationary phase group and healthy control group (all P<0.05), and the serum IFN-γ levels were lower than those in the CSU stationary phase group and healthy control group (all P<0.05). There was no statistically significant difference in the levels of the above indicators between the healthy control group and the CSU stationary group (all P>0.05). The serum levels of IL-9, PAF, total IgE, and IL-4 in the severe group were significantly higher than those in the mild and moderate groups (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild and moderate groups (all P<0.05); The serum levels of IL-9, PAF, total IgE, and IL-4 in the moderate group were significantly higher than those in the mild group (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild group ( P<0.05). Pearson correlation analysis showed that serum IL-9 and PAF levels were positively correlated with serum total IgE and IL-4 levels in CSU active phase patients (IL-9: r=0.726, 0.870, PAF: r=0.788, 0.795, all P<0.01), and negatively correlated with serum IFN-γ levels (IL-9: r=-0.831, PAF: r=-0.816, all P<0.01). Conclusions:The serum levels of IL-9 and PAF in patients with active CSU are elevated and correlated with total IgE, IFN-γ, and IL-4 levels, suggesting that IL-9 and PAF may be related to the occurrence and development of CSU.

Objective:To summarize clinical features of Kaposi′s sarcoma with a single skin lesion as the initial manifestation, and to analyze causes of its misdiagnosis.Methods:Data were retrospectively collected from 12 patients with Kaposi′s sarcoma with a single skin lesion as the initial manifestation in the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2020 to January 2022. Clinical and histopathological features and causes of misdiagnosis were analyzed.Results:Among the 12 patients, 10 were males and 2 were females; 9 were of Uyghur nationality, and 3 were of Kazakh nationality; their ages ranged from 20 to 76 years, and 10 patients were aged ≥ 60 years. Skin lesions were mostly located on the feet (8 cases), including the lateral edge of the foot (3 cases), the sole of the foot (2 cases), the ankle (1 case), the dorsal side of the third toe (1 case), and the interdigital regions between the third and fourth toes (1 case) ; skin lesions were also observed on the fibular side of the right lower limb (2 cases), on the right side of the dorsal tongue (1 case), and on the dorsal side of the right little finger (1 case). The skin lesions manifested as purple-red nodules in 9 cases, dark-red nodules in 2 cases, and purple-red plaques in 1 case, with maximum diameters of 0.5 - 3.0 (1.9 ± 0.83) cm. Skin lesions were accompanied by pain in 6 cases and by pruritus in 1 case. Histopathologically, skin lesions manifested as the proliferation of vascular endothelial cells, which could form obvious vascular cavity, or presented as a large number of proliferative spindle cells depending on the degree of tumor differentiation; immunohistochemical study showed that all the 12 patients were positive for human herpes virus 8; immunohistochemical staining of CD34 and CD31 was performed in 11 and 4 patients respectively, all the 11 patients were positive for CD34, and all the 4 patients were positive for CD31. Among the 11 patients presenting with nodules, 6 were initially misdiagnosed with skin infection, 2 with hemangioma, 2 with cutaneous squamous cell carcinoma, and 1 with dermatofibroma; the 1 patient presenting with plaques was initially misdiagnosed with psoriasis; 8 patients were first diagnosed in the department of dermatology, 3 in the department of burns, and 1 was first diagnosed in the department of maxillofacial surgery.Conclusion:The Kaposi′s sarcoma initially manifesting as a single skin lesion was more common in males aged over 60 years, usually occurred on the feet, especially on the lateral edge of the foot, and mainly manifested as purple-red nodules; half of the patients were accompanied by pain; it was frequently misdiagnosed as skin infection in clinical practice, but histopathological examination could be helpful for its differential diagnosis.

The occurrence and development of human malignancies is often accompanied by epigenetic changes, and DNA methylation is one of the most common epigenetic modification. Methylation events are often discovered in the early stage of gynecologic neoplasia. The methylation detection protocol based on liquid biopsy technology has made important progress in the screening and prognosis assessment of gynecologic tumors. The reliability of methylation detection in micro-noninvasive samples from multiple sources is similar to or better than that of traditional protocols and strategies. This article reviews the progress of methylation detection in screening, diagnosis and monitoring of gynecologic tumors, and discusses its value in the present and future diagnosis and treatment of gynecologic tumors.