OBJECTIVES: To explore the efficacy and adverse reactions of nusinersen combined with risdiplam in the treatment of spinal muscular atrophy (SMA). METHODS: A retrospective analysis was conducted on the clinical data of 10 pediatric SMA patients treated with nusinersen combined with risdiplam at the Children's Medical Center of Xiangya Hospital, Central South University. RESULTS: Among the 10 SMA patients, there were 4 with type I, 4 with type II, and 2 with type III. Nine patients initially received nusinersen monotherapy, while 1 patient received nusinersen combined with risdiplam. The median duration of combination therapy with nusinersen and risdiplam for the 10 patients was 10.5 months (range: 0.5-20.0 months), with 6 patients undergoing combination therapy for more than 6 months, showing improvements in motor and/or respiratory function. The remaining 4 patients had combination treatment durations of 0.5, 1.0, 1.3, and 4.0 months, respectively, with no significant overall improvement. After combined treatment, 5 patients experienced skin hyperpigmentation, 2 had lumbar puncture site pain, 1 experienced vomiting, 1 had increased sputum production, and 1 had reduced total sleep time. All adverse reactions were mild and did not require medical intervention. CONCLUSIONS Nusinersen combined with risdiplam demonstrates efficacy in the treatment of SMA, and no significant adverse reactions have been observed.
Humans ; Oligonucleotides/adverse effects* ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Infant ; Muscular Atrophy, Spinal/drug therapy* ; Drug Therapy, Combination ; Child ; Azo Compounds ; Pyrimidines

The patient was a girl, aged 10 years, who was admitted due to fever for 5 days and pancytopenia in peripheral blood for 2 days. Bone marrow examination showed the presence of phagocytic activity, and peripheral blood tests showed pancytopenia, an increase in ferritin, a reduction in fibrinogen, increases in triglyceride and sCD25, and a reduction in natural killer cell activity, which led to the diagnosis of hemophagocytic lymphohistiocytosis (HLH). On the day of admission, the child developed convulsions and rapidly progressed to refractory status epilepticus, which was consistent with the manifestations of febrile infection-related epilepsy syndrome. HLH was controlled after active immunotherapy, with the sequela of refractory epilepsy, and her cognitive function was essentially within normal limits. This article reports the condition of febrile infection-related epilepsy syndrome caused by HLH for the first time in China, in order to improve the awareness of this disease among clinicians.
Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Female ; Child ; Epilepsy/etiology* ; Fever/etiology* ; Epileptic Syndromes/etiology*

OBJECTIVE: To investigate the clinical characteristics and prognosis of primary pulmonary lymphoma (PPL). METHODS: The clinical data of 17 patients with PPL admitted to Gansu Provincial Hospital from January 2013 to June 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: The median age of the 17 patients was 56 (29-73) years old. There were 8 males and 9 females. According to Ann Arbor staging system, there were 9 patients with stage I-II and 8 patients with stage III-IV. There were 14 patients with IPI score of 0-2 and 3 patients with IPI score of 3-4. All 17 patients had symptoms at the initial diagnosis, most of the first symptoms were cough, and 6 patients had B symptoms.Among the 17 patients, there were 8 cases of diffuse large B-cell lymphoma (DLBCL), 5 cases of mucosa-associated lymphoid tissue (MALT) lymphoma, 1 case of gray zone lymphoma (GZL), and 3 cases of Hodgkin's lymphoma (HL). 15 patients received chemotherapy, of which 3 cases received autologous hematopoietic stem cell transplantation(ASCT) and 3 cases received radiotherapy; 2 patients did not receive treatment. The median number of chemotherapy courses was 6(2-8). The short-term efficacy was evaluated, 12 patients achieved complete remission (CR) and 3 patients achieved partial remission (PR). The age, pathological subtype, sex, Ann Arbor stage, β₂-microglobulin(β₂-MG) level, lactate dehydrogenase(LDH) level were not correlated with CR rate (P >0.05), while IPI score was correlated with recent CR rate (P < 0.05 ). The median follow-up time was 31(2-102) months. One of the 12 CR patients died of COVID-19, and the rest survived. Among the 3 patients who did not reach CR, 1 died after disease progression, while the other 2 survived. One of the 2 untreated patients died one year after diagnosis. Both the median progression-free survival (PFS) time and overall survival (OS) time of the 17 patients were both 31 (2-102) months. CONCLUSION The incidence of PPL is low, and the disease has no specific clinical manifestations, which is easily missed and misdiagnosed. The pathological subtypes are mainly MALT lymphoma and DLBCL, and the treatment is mainly combined chemotherapy. The IPI score is related to the treatment efficacy.
Humans ; Middle Aged ; Male ; Female ; Adult ; Prognosis ; Aged ; Lung Neoplasms/therapy* ; Retrospective Studies ; Neoplasm Staging ; Lymphoma/therapy* ; Lymphoma, Large B-Cell, Diffuse

Objective: To determine the clinical efficacy of platelet-rich plasma (PRP) injection combined with warm acupuncture and moxibustion for treating patients with knee osteoarthritis and cold dampness obstruction syndrome. Methods: One hundred and twenty-eight patients with knee osteoarthritis and cold dampness obstruction syndrome who visited the Rehabilitation Department and Orthopedics Department of the Second Affiliated Hospital of Anhui University of Chinese Medicine from January 2023 to March 2024 and who met the inclusion and exclusion criteria were randomly divided into an experimental (n=64) and control group (n=64) using the random number table method. The experimental group was treated with PRP injection combined with warm acupuncture and moxibustion, whereas the control group was treated with normal saline injection combined with warm acupuncture and moxibustion treatment. PRP and normal saline injections were administered once every two weeks, a total of four times. Patients were treated with warm acupuncture and moxibustion once a day, six times a week, for four consecutive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Traditional Chinese Medicine (TCM) syndrome, visual analog scale (VAS), and Lysholm scores were determined before treatment, at week 4 and week 8 of treatment, and week 16 of follow-up. Serum interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG), bone gla protein(BGP), and cartilage oligomeric matrix protein (COMP) levels were compared between the two groups before and after 8 weeks of treatment. The clinical efficacy and safety indicators between the two groups were also compared. Results: There was no statistical difference in baseline data such as gender, age, disease duration, and body mass index between the two groups of patients. Compared with before treatment, both groups showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm scores at 4, 8, and 16 weeks after treatment. After treatment, serum IL-6, MMP-3, TNF-α, and COMP levels decreased, whereas serum OPG and BGP levels increased (P<0.05). Compared with the control group, patients in the experimental group showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm score at 4, 8, and 16 weeks after treatment. Compared with the control group, patients in the experimental group showed decreased serum IL-6, MMP-3, TNF-α, and COMP levels and an increase in serum OPG and BPG levels after treatment (P<0.05). The total effective rate of the experimental group was 91.94%, higher than that of the control group (81.97%; P<0.05). Conclusion PRP injection combined with warm acupuncture and moxibustion can improve various TCM symptoms, improve knee joint function and bone metabolism, and reduce inflammation in patients with knee osteoarthritis and cold dampness obstruction syndrome.

ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases

To investigate the impact and underlying mechanism of NOP2/Sun RNA methyltransferase 2 (NSUN2) on gastric cancer progression, TCGA database was used and revealed a significant upregulation of NSUN2 expression in gastric cancer tissues. Western blot analysis revealed that NSUN2 was upregulated in gastric cancer cells compared with gastric mucosal epithelial cells. Colony formation assays demonstrated an enhanced colony-forming capacity in NSUN2-overexpressing cells. Furthermore, Transwell assays showed a marked increase in cell migration and invasion upon high NSUN2 expression. Moreover, TCGA database analysis suggested ARMC9 as a potential downstream target of NSUN2. Subsequently, MeRIP-qPCR analysis revealed that NSUN2 overexpression could increase m5C modification of ARMC9 mRNA, and reduce its degradation rate, thus enhancing protein expression. Additionally, ARMC9 overexpression augmented cellular colony formation and migratory and invasive capabilities. These findings indicate that NSUN2 promotes gastric cancer progression by elevating m5C modification of ARMC9 mRNA, increasing its stability and enhancing its expression, therefore, NSUN2 and ARMC9 may serve as potential therapeutic targets for gastric cancer.

Objective To construct and validate a risk prediction model for in-hospital death af-ter successful resuscitation in patients with cardiac arrest.Methods A retrospective study was con-ducted on 295 patients with cardiac arrest who successfully restored spontaneous circulation after car-diopulmonary resuscitation and were further treated in hospital.The patients were divided into training and validation sets using K-fold cross-validation and then grouped and compared based on whether in-hospital death occurred.A binary Logistic regression analysis was used to screen risk prediction fac-tors,and a nomogram prediction model was constructed.The model performance was evaluated and validated in the training and validation sets,respectively.Results The results of the multivariate Logistic regression analysis showed that hospitalization duration(OR=1.180;95％CI,1.080 to 1.280;P＜0.001),norepinephrine dose(OR=0.980;95％CI,0.970 to 0.990;P=0.002),ini-tial respiratory rate after resuscitation(OR=1.090;95％CI,1.030 to 1.150;P=0.004),and sinus rhythm recovery after resuscitation(OR=4.280;95％CI,1.670 to 10.980;P=0.003)were inde-pendent influencing factors for in-hospital death.A nomogram model was constructed based on these in-dependent influencing factors,and it was verified that the model had good discrimination,calibration,applicability,and rationality.Conclusion The influencing factors for in-hospital death after successful resuscitation in patients with cardiac arrest include hospitalization duration,norepinephrine dose,initial respiratory rate after resuscitation,and sinus rhythm recovery after resuscitation.The nomo-gram model constructed based on these factors can provide a reference for clinical decision-making.

Objective To analyze the influencing factors of plastic bronchitis in children with Mycoplasma pneumoniae infection and put forward targeted prevention suggestions. Methods The clinical data of children with Mycoplasma pneumoniae infection who were admitted to Chengdu Third People's Hospital from September 2022 to February 2024 were retrospectively analyzed . According to whether plastic bronchitis occurred, they were divided into plastic group (n=118) and non-plastic group (n=184), and the differences between the two groups were compared and analyzed. Univariate and multivariate logistics regression analysis equations were used to analyze the independent influencing factors of plastic bronchitis in children with mycoplasma pneumoniae infection. Results Among the 302 children with Mycoplasma pneumoniae infection , 118 cases were diagnosed with plastic bronchitis. Analysis showed that the children’s age, duration of fever, hospital stay, pleural effusion rate, number of bronchoscopic lavage, allergy history, endoscopic mucosal erosion rate, WBC, NE%, LY%, CRP, LDH, PCT and D-D were the single factors influencing the occurrence of plastic bronchitis in children with mycoplasma pneumoniae infection. Binary logistics regression analysis revealed that age (OR=2.137, P=0.033, 95% CI: 1.132-16.603), allergy history （OR=3.028, P=0.014, 95% CI: 1.261-864), NE% (OR=2.395, P=0.031, 95% CI: 1.087-5.274), CRP (OR=3.864, P=0.004, 95% CI: 1.563-3.864), PCT (OR=4.125, P=0.001, 95% CI: 1.793-3.864), and D-D (OR=3.920, P=0.002, 95% CI: 1.632-3.864) were independent risk factors for plastic bronchitis in children with mycoplasma pneumoniae infection (P<0.05). Conclusion Age, allergy history, NE%, CRP, PCT and D-D are independent risk factors for plastic bronchitis in children with mycoplasma pneumoniae infection . It is necessary to take clinical intervention measures to reduce the occurrence risk.

Aim To systematically analyze the risk factors for comorbid ischemic cardiovascular and cerebrovas-cular diseases using principal component analysis.It seeks to identify key risk factors influencing comorbidity and to con-struct a predictive model to serve as a screening tool for the prevention and management of comorbidities.Methods This retrospective study included patients diagnosed with coronary artery disease from December 1,2009 to June 30,2020,at the First Affiliated Hospital of Xinjiang Medical University,using data from the hospital's integrated coronary heart dis-ease prevention platform.Patients were divided into two groups:those with both cardiovascular and cerebrovascular disea-ses and those with only coronary artery disease based on inclusion and exclusion criteria.Clinical indicators during hospi-tal admission were collected.The sample was randomly divided into a modeling set and a validation set in a 7∶3 ratio.In the modeling set,principal component analysis was used to explore the distribution differences in risk factors between the comorbid group and the single-disease group.By analyzing factor load contributions,the most significant variables were i-dentified.Logistic regression was then used to construct a predictive model,and a nomogram was generated.The model's predictive ability and robustness were evaluated in the validation set.Results A total of 11 808 participants were included,with 2 781(23.6%)in the comorbid group and 9 027(76.4%)in the coronary heart disease-only group.Compared with the single-disease group,the comorbid group had a higher average age,a greater proportion of females,and higher systolic blood pressure levels at admission(P<0.001).Additionally,thelevelsof hemoglobin,platelet distri-bution width,low density lipoprotein,and blood sodium were significantly higher in the comorbid group(P<0.05).A total of 8 265 participants were randomly assigned to the modeling set.Principal component analysis identified seven key factors with factor load contributions greater than 5:sodium level,systolic blood pressure,diastolic blood pressure,age,hemoglobin concentration,platelet distribution width,and total bilirubin level.Using these factors,a nomogram was con-structed via Logistic regression.The nomogram's area under the receiver operating characteristic curve for predicting co-morbid ischemic cardiovascular and cerebrovascular diseases was 0.630(95%CI:0.600～0.768,P<0.001).A total of 3 543 participants were randomly assigned to the validation set.In the validation set,the receiver operating characteristic curve was 0.628.Conclusion Elevated sodium level,higher systolic and diastolic blood pressure at admission,older age,increased hemoglobin concentration,higher platelet distribution width,and lower total bilirubin level are risk factors for comorbid ischemic cardiovascular and cerebrovascular diseases.The nomogram constructed has clinical value for screening patients with such comorbidities.