Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P＜0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P＜0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective: To compare quality control (relative purity and specific activity) and process control [plasminogen (Pg) antigen recovery and potency recovery] indexes of samples before and after adding the Q chromatography step to the full chromatography process of human Pg, thereby determining whether the addition of this step could improve Pg recovery by affinity chromatography. Methods: A Q chromatography step was added before the Pg affinity chromatography in the original Pg chromatography process. The loading solution, flow through solution and eluate of Q chromatography and Pg affinity chromatography were collected. The potency of coagulation factor Ⅱ (FⅡ), Ⅶ (FⅦ), Ⅷ (FⅧ), Ⅸ (FⅨ), and Ⅹ(FⅩ) were detected by the coagulation method, the total protein content was detected by the BCA method, and the Pg potency was detected by the chromogenic substrate method. The content of specific plasma proteins was detected by immunoturbidimetry, the potency recovery of coagulation factors was calculated, and the flow direction of coagulation factors was analyzed. The recovery of different plasma protein antigens were calculated, and the distribution of impurity proteins was analyzed. The relative purity and specific activity of Pg, antigen content, and potency recovery in the target fractions were calculated and compared with the original process indicators, so as to determine the effect of adding Q chromatography on the original process. Furthermore, the reproducibility after process modification was assessed. Results: 100% of FⅡ, FⅩ, and FⅨ, 87.81% of FⅧ, and 40.44% of FⅦ in filtered plasma were removed by Q chromatography. The residual FⅦ (53.26%) and FⅧ (13.30%) in Q flow-through fraction were completely removed by Pg affinity chromatography. In both the original process (without Q-chromatography) and the modified process (with Q-chromatography), non-target plasma proteins mainly existed in the flow-through fraction of Pg affinity chromatography. The antigen recovery of IgM, ceruloplasmin (CER), and fibronectin (FNC) in Q-chromatography flow-through fraction were reduced. In contrast, antigen recovery of other plasma proteins [IgG, IgA, Pg, albumin (AlB), alpha-1-antitrypsin (AAT), and fibrinogen (Fg)] were all >90%, which were consistent with the protein composition and proportion in the original affinity chromatography loading solution. Compared with the recovery rate of Pg antigen in the original process (74.4%), the total recovery of Pg antigen in the modified process was significantly increased (89.97%). Compared with the recovery of IgG (97.48%) and Fg (95.32%) in the Pg affinity flows-through fraction of the original process, the modified process resulted in a slight reduction in the recovery of IgG (94.60%), while the recovery of Fg was not affected (95.05%). The potency recovery rate, specific activity, and relative purity of Pg after Q chromatography were 99.3%, 0.016 U/mg, and 0.15%. These values were the same as those of Pg affinity chromatography loading solution by the original process, indicating that introduction of Q chromatography did not affect subsequent Pg affinity chromatography. Compared with the recovery of Pg antigen in three batches of the original process (66.49±1.02)%, the recovery of Pg antigen in the affinity chromatography eluent of the modified process [five batches; (77.43±4.43)%] was significantly improved. Furthermore, the potency recovery was (86.80±4.28)%, the relative purity was (81.99±1.25)%, the specific activity was (8.679±1.073)U/mg, and the process was reproducible. Conclusion: The addition of Q chromatography could improve the recovery of Pg affinity chromatography in the full chromatography process.

Objective To explore the correlation between malignant tumors and serum N-terminal pro-brain natriuretic peptide(NT-proBNP)levels.Methods A total of 336 patients with malignant tumors(cancer group)who were admitted to the Department of Cardiology,Chinese PLA General Hospital and underwent coronary angiography from January 1,2009 to December 31,2020,and were newly diagnosed and had not received any anti-tumor treatment were selected.They were matched with 1 008 patients(non-cancer group)in a 1:3 ratio using propensity score matching based on gender and age.Clinical data of the patients were collected,including age,gender,serum NT-proBNP,left ventricular ejection fraction(LVEF),SYNTAX score,serum creatinine,and tumor diagnosis information.The patients were divided into 4 groups based on the quartiles of NT-proBNP levels:low-level group(NT-proBNP ≤ 61.80 pg/mL),medium-level group(61.80 pg/mL＜NT-proBNP≤ 152.95 pg/mL),high-level group(152.95 pg/mL＜NT-proBNP≤470.10 pg/mL),and very high-level group(NT-proBNP＞470.10 pg/mL).Ordered logistic regression analysis was used to analyze the correlation between malignant tumors and serum NT-proBNP.Results A total of 1 344 patients were included,with an average age of(65.78±9.18)years old,1 003 males(74.63％),LVEF of 60.00％(55.00％,64.00％),SYNTAX score of(13.84±11.63)points,and creatinine level of 76.60(66.50,88.88)μmol/L.Among the 336 cancer patients,the top 3 types of cancer were lung cancer(84 cases,25.00％),colorectal cancer(58 cases,17.26％),and gastric cancer(52 cases,15.48％).The NT-proBNP levels in the cancer group were significantly higher than those in the non-cancer group(208.45[85.75,601.83]pg/mL vs 134.35[57.18,430.23]pg/mL,P＜0.001).Ordered logistic regression analysis showed that in the unadjusted model,malignant tumors were significantly associated with higher NT-proBNP levels(OR=1.561,95％CI 1.538-1.584,P＜0.001);after adjusting for relevant factors,malignant tumors remained significantly associated with higher serum NT-proBNP levels(OR=1.384,95％CI 1.070-1.791,P=0.013).Conclusions NT-proBNP in malignant tumor patients is higher than that in non-malignant tumor patients,and there is a significant correlation between malignant tumors and serum NT-proBNP levels.

[Objective] To determine the feasibility of preparing plasminogen (Pg) with Fraction Ⅲ precipitation (hereinafter referred to as FⅢ-P) from low-temperature ethanol process by full chromatography (hereinafter referred to as FⅢ-P process). [Methods] The FⅢ-P was diluted with dissolution buffer at different dilution times and stirring time. The potency and antigen concentration of Pg in dissolution sample were detected and the dissolution and clarification conditions were determined. Pre-treatment of loading sample and pre-experiment of affinity chromatography were carried out on the FⅢ-P dissolution sample to judge whether the loading sample had an impact on the chromatography by observing the performance of the affinity chromatography column and to evaluate whether the affinity chromatography could achieve the purpose of purifying Pg by detecting the plasma protein antigen concentration and Pg potency of the samples in the process. Two batches of FⅢ-P process were studied step by step, and the specific activity, steps and total recovery, and the output of Pg per ton of plasma were calculated. The feasibility of preparing Pg by FⅢ-P process was evaluated by comparing with the data of full chromatography process using plasma as raw material (hereinafter referred to as plasma process). [Results] The FⅢ-P was dissolved with 10 times of dissolution buffer, stirred for 1 hour, centrifuged at room temperature of 10 000×g for 15 minutes. The supernatant was first filtered with a screen, then clarified with an 8/0.8 μm filter, and finally filtered with a 0.45/0.2 μm filter and loaded. Pre-test showed that from clarification and filtration to Pg affinity chromatography, the step recovery of activity and antigen was 39.51% and 108.64%, respectively, the antigen concentration of Pg increased by 31.16 times and the activity increased by 11.39 times after affinity chromatography, which reaching the effect of affinity chromatography purification of Pg. The results of 2 batches of step-by-step scale-up FⅢ-P process showed that the total recoveries of antigen and activity from plasma to SP chromatography of FⅢ-P process were (45.76±1.10)% and (24.15±0.59)%, respectively, which had a total loss of about 1/3 of antigen and about 2/3 of activity compared to the plasma process. The Pg specific activity of SP chromatography eluent was (4.68±0.25) U/mg, which was about half of that of plasma process, but meeted the internal standard of > 4 U/mg. The output of Pg antigen per ton of plasma in the FⅢ-P process was 68.73% of that in the plasma process, and the output of Pg activity per ton of plasma in the plasma process was 29.82% of that in the plasma process, which basically achieved the purpose of waste utilization of FⅢ-P. [Conclusion] The technical route of preparing Pg from FⅢ-P by full chromatography is feasible.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

OBJECTIVE To explore the expression changes of TLR4/MyD88/NF-κB signaling pathways in olfactory disorders.METHODS There were 40 healthy BALB/c mice who were divided into an observation group and a control group,with 20 mice in each group.Detection of Toll-like receptors(TLR4),myeloid differentiation primary response gene 88(MyD88)and nuclear factor kappa B(NF-κB)in mice using quantitative reverse transcription PCR level;Detection of TLR4,MyD88 and NF-κB by Western blot(WB)test protein content;Immunohistochemical detection of the expression of mouse olfactory marker protein(OMP).RESULTS There was no significant difference in foraging time between the two groups of mice before modeling(P>0.05),after modeling,the foraging time of the observation group mice was significantly longer than that of the control group(P<0.05);The relative mRNA expression level of TLR4,MyD88 and NF-κB in the nasal epithelium of mice in the observation group was significantly higher than that of the control group(P<0.05);The protein expression of TLR4,MyD88 and NF-κB in the nasal epithelium of mice in the observation group was significantly higher than that of the control group(P<0.05);The level of OMP protein in the nasal epithelium of the observation group was significantly lower than that of the control group(P<0.05).CONCLUSION Expression reinforcement of TLR4/MyD88/NF-κB signaling pathway in a mouse model of olfactory dysfunction.

Objective:To evaluate the reliability of a region-locked 3D-printed template combined with a bi-directional matching scheme in assistance of screw placement for thoracolumbar fractures.Methods:From January 2019 to March 2023, 52 patients with thoracolumbar fracture were treated at Department of Orthopedics, The People's Hospital of Liyang. They were 29 males and 23 females, with an age of (58.2±13.3) years. They were divided into a template group and a free-hand group according to the different screw placements. In the template group of 25 cases, a region-locked 3D-printed template combined with a bi-directional matching scheme was used to assist the pedicle positioning; in the free-hand group of 27 cases, the free hand screw placement was assisted only by image data and C-arm fluoroscopy. The operation time, intraoperative fluoroscopy frequency, intraoperative blood loss, complications, and placement accuracy were compared between the 2 groups. Visual analogue scale (VAS), Oswestry disability index (ODI), and anterior height ratio of the injured vertebra were compared between preoperation, 1 week postoperation, and the final follow-up, as well as between the 2 groups.Results:There were no statistically significant differences in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All patients were followed up for (11.2±4.2) months. The differences were not statistically significant between the 2 groups in intraoperative blood loss, rate of complications, VAS or ODI at preoperation, 1 week postoperation, or the final follow-up, or in anterior height ratio of the injured vertebra ( P>0.05). In the template group, the operation time [(80.1±18.5) min] was significantly longer than that in the free-hand group [(69.4±16.6) min], the intraoperative fluoroscopy frequency [2 (2, 3) times] significantly lower than that in the free-hand group [3 (3, 4) times], and the placement accuracy [98.4% (127/129)] significantly higher than that in the free-hand group [91.8% (112/122)] (all P<0.05). All patients showed significant improvements in VAS, ODI and anterior height ratio of the injured vertebra at postoperative 1 week compared with the preoperative values, and the improvements at the last follow-up were significantly larger than those at postoperative 1 week ( P<0.05). No injury to the spinal cord, nerve root or blood vessel was observed postoperatively. Conclusions:In the treatment of thoracolumbar fractures, the screw placement assisted by a region-locked 3D-printed template combined with a bi-directional matching scheme is better than free-hand screw placement in terms of improved accuracy and reduced fluoroscopy, but the former incurs longer operative exposure than the latter. There is no significant difference between the 2 methods of screw placement in clinical efficacy.

Objective To investigate the distribution and imaging manifestations of extrapulmonary bronchogenic cyst(BC)and to make differential diagnosis.Methods The data of 32 patients with extrapulmonary BC confirmed by pathology were collected.The lesion location,CT and MRI findings were analyzed and summarized.All patients underwent plain CT scan,and 27 of them underwent enhanced CT scan.Three patients underwent MRI plain and enhanced scan.Results Of the 32 patients,24 cases were mediastinal BC including 20 cases in the anterior mediastinum and other 4 cases in the posterior mediastinum.8 cases were ectopic BC,including 2 cases in the upper chest wall,4 cases in the gastric cardia,1 case in the greater curvature of the stomach,and 1 case in the left adre-nal gland.All lesions were single with clear boundary.The lesions were mainly round in shape(22 cases),and a few were flat/"D"shape(10 cases).There were no significant differences in the included signs between mediastinal BC and ectopic BC(P＞0.05).Nodular calcification of cyst wall was found in 2 cases.There were 4 cases with CT value＜20 HU and other 28 cases with CT value≥20 HU.The enhanced CT scan in 27 cases showed non-or mild enhancement.MRI showed hypointensity on T1WI in 2 cases,isointensity on T1WI in 1 case,hyperintensity on T2WI in 3 cases,and obvious enhancement on T1WI enhanced scan in 1 case.In addition,30 cases(93.7％)were misdiagnosed as thymic cyst(8 cases),thymoma(12 cases),neurogenic tumor(4 cases),ganglioneuroma(4 cases)and gastric stromal tumor(2 cases).Conclusion Extrapulmonary BC is rare,and most of the lesions are located near the central axis of the body with no obvious enhancement and sometimes cyst wall calcification,which has certain value for clinical diagnosis.