Schimke immuno-osseous dysplasia (SIOD)caused by SMARCAL1 gene mutations is a rare genetic disorder characterized by multi-system involvement, including T-cell dysfunction, skeletal dysplasia, disproportionate short stature, nephrotic syndrome, and kidney failure. This multidisciplinary consultation involved a 9-year-old boy with intrauterine growth retardation, presenting with short stature, T-cell lymphopenia, proteinuria, and degenerative bone and joint disease. Treatment primarily focused on symptomatic and supportive care. Through the multidisciplinary rare disease consultation, holistic support was provided to the patient, offering comprehensive care from various specialtiesx.We also aim to use this case report to enhance clinicians′ under-standing of SIOD and improve the management and treatment of rare diseases.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Objective Clinical medical record data associated with hepatitis B-related acute-on-chronic liver failure(HBV-ACLF)generally have small sample sizes and a class imbalance.However,most machine learning models are designed based on balanced data and lack interpretability.This study aimed to propose a traditional Chinese medicine(TCM)diagnostic model for HBV-ACLF based on the TCM syndrome differentiation and treatment theory,which is clini-cally interpretable and highly accurate. Methods We collected medical records from 261 patients diagnosed with HBV-ACLF,includ-ing three syndromes:Yang jaundice(214 cases),Yang-Yin jaundice(41 cases),and Yin jaun-dice(6 cases).To avoid overfitting of the machine learning model,we excluded the cases of Yin jaundice.After data standardization and cleaning,we obtained 255 relevant medical records of Yang jaundice and Yang-Yin jaundice.To address the class imbalance issue,we employed the oversampling method and five machine learning methods,including logistic regression(LR),support vector machine(SVM),decision tree(DT),random forest(RF),and extreme gradient boosting(XGBoost)to construct the syndrome diagnosis models.This study used precision,F1 score,the area under the receiver operating characteristic(ROC)curve(AUC),and accuracy as model evaluation metrics.The model with the best classification per-formance was selected to extract the diagnostic rule,and its clinical significance was thor-oughly analyzed.Furthermore,we proposed a novel multiple-round stable rule extraction(MRSRE)method to obtain a stable rule set of features that can exhibit the model's clinical in-terpretability. Results The precision of the five machine learning models built using oversampled balanced data exceeded 0.90.Among these models,the accuracy of RF classification of syndrome types was 0.92,and the mean F1 scores of the two categories of Yang jaundice and Yang-Yin jaun-dice were 0.93 and 0.94,respectively.Additionally,the AUC was 0.98.The extraction rules of the RF syndrome differentiation model based on the MRSRE method revealed that the com-mon features of Yang jaundice and Yang-Yin jaundice were wiry pulse,yellowing of the urine,skin,and eyes,normal tongue body,healthy sublingual vessel,nausea,oil loathing,and poor appetite.The main features of Yang jaundice were a red tongue body and thickened sublin-gual vessels,whereas those of Yang-Yin jaundice were a dark tongue body,pale white tongue body,white tongue coating,lack of strength,slippery pulse,light red tongue body,slimy tongue coating,and abdominal distension.This is aligned with the classifications made by TCM experts based on TCM syndrome differentiation and treatment theory. Conclusion Our model can be utilized for differentiating HBV-ACLF syndromes,which has the potential to be applied to generate other clinically interpretable models with high accura-cy on clinical data characterized by small sample sizes and a class imbalance.

Actinomycosis is a rare chronic granulomatous disease characterized by granuloma formation and tissue fibrosis with sinus tracts,often misdiagnosed due to its similarity to many infectious and non-infectious diseases.This report presents a case of a 60-year-old female with more than 10 years history of rheumatoid arthritis who developed actinomycosis infection after long-term treatment with immunosuppressants and biologics,including methotrexate,leflunomide,and infliximab,leading to recurrent joint pain,poorly controlled rheumatoid arthritis activity,and persistent elevation of white blood cell counts.Abdominal CT revealed a pelvic mass and right ureteral dilation.Pathological examination of cervical tissue showed significant neutrophil infiltration and sulfur granules,indicating actinomycosis.The patient received 18 months of doxycycline treatment for the infection and continued rheumatoid arthritis therapy with leflunomide,hydroxychloroquine sulfate,and tofacitinib,resulting in improved joint symptoms and normalized white blood cell counts.After 2 years of follow-up,the patient remained stable with no recurrence.This case highlights the importance of clinicians being vigilant for infections,particularly chronic,occult infections from rare pathogens,in rheumatoid arthritis patients on potent immunosuppressants and biologics,advocating for early screening and diagnosis.

Increasing prevalence and incidence of diabetes mellitus(DM)-the most common chronic consumptive disease worldwide-has a devastating impact on people's daily lives, particularly through the deterioration or complete loss of vision brought on by diabetic retinopathy(DR). Therefore, it is imperative to investigate the pathogenesis and effective treatment of DR. Meanwhile, Pueraria lobata is the extensively used dried root of kudzu or dried kudzu, also known as Pueraria flavonoids. Moreover, its roots are primarily composed of isoflavones, Pueroside ABC, triterpenes, and alkaloids, which can calm cardio-cerebrovascular smooth muscle and enhance microcirculation. Currently, it is widely employed for the treatment of cardio-cerebrovascular diseases, osteonecrosis, DM and its complications, neurodegenerative disorders, endometriosis and tumor diseases. Inhibiting retinal neovascularization, alleviating ischemia and hypoxia, decreasing advanced glycation end products in diabetes, raising insulin-like growth factor(IGF)expression while decreasing tumor necrosis factor-α(TNF-a)expression, decreasing vascular endothelial growth factor(VEGF)expression, reducing retinal nerve cell death, inhibiting the NOD-like receptor protein 3(NLRP3)inflammatory pathway and inhibiting ferroptosis are all mechanisms by which puerarin(Pue)has been found to protect the retina in recent studies. Thus, this article summarizes the current comprehension of the mechanism and protective effect of Pue on diabetic retina, serving as a guidepost for its future development and application.

Objective To investigate the cardiac structural and functional characteristics in the patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM),and predict the factors influencing the characteristics. Methods A total of 783 HFpEF patients diagnosed in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from April 2009 to December 2020 were enrolled in this study.Echocardiography and tissue Doppler technique were employed to evaluate cardiac structure and function.According to the occurrence of T2DM,the patients were assigned into a HFpEF+T2DM group (n=332) and a HFpEF group (n=451).Propensity score matching (PSM)(in a 1∶1 ratio) was adopted to minimize confounding effect.According to urinary albumin excretion rate (UAER),the HFpEF+T2DM group was further divided into three subgroups with UAER<20 μg/min,of 20-200 μg/min,and>200 μg/min,respectively.The comorbidities,symptoms and signs,and cardiac structure and function were compared among the groups to clarify the features of diabetes related HFpEF.Multivariate linear regression was conducted to probe the relationship of systolic blood pressure,blood glucose,glycosylated hemoglobin,and UARE with cardiac structural and functional impairment. Results The HFpEF+T2DM group had higher prevalence of hypertension (P=0.001) and coronary heart disease (P=0.036),younger age (P=0.020),and larger body mass index (P=0.005) than the HFpEF group,with the median diabetic course of 10 (3,17) years.After PSM,the prevalence of hypertension and coronary heart disease,body mass index,and age had no significant differences between the two groups(all P>0.05).In addition,the HFpEF+T2DM group had higher interventricular septal thickness (P=0.015),left ventricular posterior wall thickness (P=0.040),and left ventricular mass (P=0.012) and lower early diastole velocity of mitral annular septum (P=0.030) and lateral wall (P=0.011) than the HFpEF group.Compared with the HFpEF group,the HFpEF+T2DM group showed increased ratio of early diastolic mitral filling velocity to early diastolic mitral annular velocity (E/e') (P=0.036).Glycosylated hemoglobin was correlated with left ventricular mass (P=0.011),and the natural logarithm of UAER with interventricular septal thickness (P=0.004),left ventricular posterior wall thickness (P=0.006),left ventricular mass (P<0.001),and E/e' ratio (P=0.049). Conclusion The patients with both T2DM and HFpEF have thicker left ventricular wall,larger left ventricular mass,more advanced left ventricular remodeling,severer impaired left ventricular diastolic function,and higher left ventricular filling pressure than the HFpEF patients without T2DM.Elevated blood glucose and diabetic microvascular diseases might play a role in the development of the detrimental structural and functional changes of the heart.
Humans ; Aged ; Heart Failure/diagnosis* ; Diabetes Mellitus, Type 2 ; Stroke Volume ; Glycated Hemoglobin ; Blood Glucose ; Propensity Score ; Ventricular Function, Left ; Hypertension

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

OBJECTIVES: To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis. METHODS: Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed. RESULTS: A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P<0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P>0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×10⁹/L at diagnosis was an influencing factor for 5-year OS rate in children with JMML (P<0.05). CONCLUSIONS The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.
Child ; Humans ; Male ; Female ; Child, Preschool ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Prognosis ; Genetic Testing ; Mutation ; Hematopoietic Stem Cell Transplantation

Abstract: Objective　To investigate the relationship between the body mass index (BMI) levels and the negative conversion time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid in adult coronavirus disease 2019 (COVID-19) patients and the asymptomatic persons. Methods　Asymptomatic infected patients and confirmed COVID-19 patients admitted to Chengdu Public Health Clinic Center from February 2021 to November 2021 were dynamically included. The epidemiological and clinical characteristics of the objects were collected, and the SARS-CoV-2 nucleic acid testing of the objects during their hospitalization was continuously monitored, and the negative nucleic acid conversion time was recorded. The t test or Wilcoxon rank sum test, χ2 test or Fisher's exact probability method examine were used to distribute characteristics of each group of variables and the connection between different variables, respectively. Then the variables showed differences in distribution (P<0.05) between different BMI groups were included in the multivariate Cox proportional risk regression model. Results　A total of 253 subjects ranged from 18 to 63 years old, with M(P25, P75) age of 37.0 (30.0, 47.0) years old, were included in this study. The male to female ratio was 4.16 to 1. The BMI was (23.97±3.33) kg/m2. 50.59% (128/253) of the objects were overweight or obese, and 78.13% (100/128) were overweight. The negative time of SARS-CoV-2 nucleic acid conversion of all subjects ranged from 1 to 71 days, with M(P25, P75) of 7.0 (2.0, 18.0) days (P<0.001). The negative time of SARS-CoV-2 nucleic acid conversion of the normal weight or the thin, and the overweight or obese were 5.00 (2.00, 19.00) and 8.00 (2.00, 17.75) days respectively. The results of multivariate Cox's proportional hazards regression model showed that the BMI levels may not be associated with the negative conversion time of SARS-CoV-2 nucleic acid (HR=1.090, 95%CI: 0.843-1.410, P=0.510). Conclusions　Adult asymptomatic persons and confirmed COVID-19 patients are mainly middle-aged and young males, and overweight or obesity is relatively common. Overweight or obesity cannot be considered as an independent factor influencing the negative conversion time of SARS-CoV-2 nucleic acid.

OBJECTIVE: To observe the levels of soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death ligand 1 (sPD-L1) in peripheral blood of lymphoma patients, and reveal their clinical significances. METHODS: The peripheral blood specimens and clinical data of 64 newly diagnosed lymphoma patients and 30 healthy volunteers were collected. The levels of sPD-1 and sPD-L1 were detected by enzyme-linked immunosorbent assay (ELISA), and their correlations with clinical characteristics of the patients including pathological type, stage, lactate dehydrogenase (LDH) level, T cell subsets were analyzed. RESULTS: The levels of both sPD-1 and sPD-L1 in peripheral blood of lymphoma patients were higher than those of normal controls (P <0.05). There were no significant differences in sPD-1 and sPD-L1 levels in peripheral blood between Hodgkin lymphoma and non-Hodgkin lymphoma patients. Different pathological subtypes of lymphoma had different levels of sPD-1. The level of sPD-1 in patients with T-cell lymphoma was higher than that in patients with B-cell lymphoma (P =0.001). The levels of both sPD-1 and sPD-L1 in patients with Ann Arbor stage III and IV were higher than those in patients with stage I and II (P <0.05). The level of sPD-L1 in patients with abnormally increased LDH was higher than that in patients with normal LDH (P =0.001), but there was no significant difference in sPD-1 level. T cell subset analysis showed that the level of sPD-L1 was negatively correlated to CD4⁺ T cell content (r =-0.265). CONCLUSION The levels of sPD-1 and sPD-L1 in peripheral blood of lymphoma patients are related to the pathological type, Ann Arbor stage, LDH content and T cell subsets, and will be potential biomarkers in predicting the prognosis of lymphoma.
Humans ; Clinical Relevance ; Prognosis ; T-Lymphocyte Subsets/metabolism* ; Lymphoma, T-Cell, Peripheral ; Enzyme-Linked Immunosorbent Assay ; B7-H1 Antigen/metabolism*