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

This study aimed to identify ideal pharmaceutical candidates featuring strong anti-HIV-1 activity and desirable drug-like characteristics. Our endeavor involved the implementation of a bioisosterism strategy, leading to the discovery of an assemblage of halogen-containing biphenyl-diarylpyrimidines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Notably, compound A12 demonstrated exceptional efficacy against both WT HIV-1 (EC₅₀ = 1.9 nmol/L) and seven mutant strains (EC₅₀ = 1.7-157 nmol/L), surpassing that of the lead compound 6 and comparable to etravirine. Furthermore, this analog exhibited minimal adverse effects with significantly reduced cytotoxicity (CC₅₀ = 195 μmol/L) and a high selectivity index (SI = 102,608), superior to those of etravirine (CC₅₀ > 4.6 μmol/L, SI > 1436) and rilpivirine (CC₅₀ = 3.98 μmol/L, SI = 3989). It displayed low inhibition of CYP (IC₅₀ = 6.99-25 μmol/L) and hERG (IC₅₀ > 40 μmol/L), indicating a safer profile compared to etravirine and rilpivirine. No acute toxicity or organ pathological damage was observed at a single dose of 2 g/kg. Additionally, A12 exhibited favorable oral bioavailability (F = 29.2%) and an extended elimination half-life (T _1/2 = 13.56 h), enabling convenient oral administration at minimal doses. These findings indicated that A12 could serve as a promising drug candidate for HIV treatment.

Ferric oxide/nitrogen-doped carbon nanomaterials(Fe2O3/N-C)with high oxidase-like activity were successfully synthesized via the wet chemistry and pyrolysis method using pyrrole and 1,2,3,4-butanetetracarboxylic acid as raw materials and ferric chloride as the oxidant.The structure and morphology of Fe2O3/N-C were characterized by the techniques including scanning electron microscopy,surface scanning elemental analysis,X-ray diffraction,X-ray photoelectron spectroscopy,and Fourier transform infrared spectroscopy.It was revealed that Fe2O3/N-C could efficiently catalyze the conversion of colorless 3,3',5,5'-tetramethylbenzidine(TMB)into blue-colored oxidized TMB(oxTMB).Based on the principle that ascorbic acid(AA)could inhibit the catalytic color-development reaction of Fe2O3/N-C on TMB,resulting in a paler color and a reduction in the absorbance of the system,a colorimetric sensor for sensitive and accurate detection of AA was constructed.The linear range of the sensor for AA detection was 0.25-30.0 μmol/L,and the detection limit was 0.1 μmol/L.Moreover,it was successfully applied to determination of AA in beverage and tablet samples with satisfactory results.

Objective To investigate the risk factors for lymph node metastasis in resectable lung adenocarcinoma by combining spatial location, clinical, and imaging features, and to construct a lymph node metastasis prediction model. Methods A retrospective study on patients who underwent chest CT at the First Affiliated Hospital of Nanjing Medical University from June 2016 to June 2020 and were surgically confirmed to have invasive lung adenocarcinoma with or without lymph node metastasis was conducted. Patients were divided into a positive group and a negative group based on the presence or absence of lymph node metastasis. Clinical and imaging data of the patients were collected, and the independent risk factors for lymph node metastasis in resectable lung adenocarcinoma were analyzed using univariate and multivariate logistic regression. A combined spatial location-clinical-imaging feature prediction model for lymph node metastasis was established and compared with the traditional lymph node metastasis prediction model that does not include spatial location features. Results A total of 611 patients were included, with 333 in the positive group, including 172 males and 161 females, with an average age of (58.9±9.7) years; and 278 in the negative group, including 127 males and 151 females, with an average age of (60.1±11.4) years. Univariate and multivariate logistic regression analyses showed that the spatial relationship of the lesion to the lung hilum, nodule type, pleural changes, and serum carcinoembryonic antigen (CEA) levels were independent risk factors for lymph node metastasis. Based on this, the combined spatial location-clinical-imaging feature prediction model had a sensitivity of 91.67%, specificity of 74.05%, accuracy of 87.88%, and area under the curve (AUC) of 0.885. The traditional lymph node metastasis prediction model, which did not include spatial location features, had a sensitivity of 76.40%, specificity of 72.10%, accuracy of 53.86%, and AUC of 0.827. The difference in AUC between the two prediction methods was statistically significant (P=0.026). Compared with the traditional prediction model, the predictive performance of the combined spatial location-clinical-imaging feature prediction model was significantly improved. Conclusion In patients with resectable lung adenocarcinoma, those with central/inner spatial location, solid density, pleural changes with wide base depression, and elevated serum CEA levels have a higher risk of lymph node metastasis.

Objective To comprehensively excavate and analyze the research status,research hotspots and future trends of the literature related to the field of acupoint catgut embedding therapy for pain treatment in the CNKI database.Methods We searched the CNKI database from its establishment to June 2022,and scientifically analyzed the authors,keywords,and institutions of the included literature of acupoint catgut embedding therapy for pain treatment through specific algorithms of Citespace to generate a visual knowledge map.Results A total of 319 documents were included for statistical analysis,the number of publications in the field of acupoint catgut embedding therapy for the treatment of pain was generally on the rise,the number of publications by various authors was on the low side,and there was a lack of co-operation between the research teams,with the main institutions being the Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,Affiliated Hospital of Youjiang Medical Universities of Nationalities and the Guangzhou University of Chinese Medicine,forming a 10-keyword clustering,and the hotspots of diseases under study were mainly mixed haemorrhoids,postoperative pain,low back and leg pain and dysmenorrhoea,etc..The main interventions were pure acupoint catgut embedding therapy and the combination of acupoint catgut embedding therapy and other acupuncture therapies,and the main research method was clinical research.Conclusion Acupoint catgut embedding therapy for the treatment of pain has a good development prospect,the future needs to deepen the clinical research,strengthen the mechanism research,pay attention to the joint use of acupoint catgut embedding therapy and other traditional Chinese medicine methods,and pay attention to the research of different thread materials.

This study was aimed at investigating the antimicrobial susceptibility and genomic characteristics of multidrug resistant diarrheagenic Escherichia coli isolated from human and food samples in Henan Province from 2017 to 2022.A total of 101 strains of multidrug resistant diarrheagenic E.coli were subjected to antimicrobial susceptibility testing with the broth di-lution method.Whole genome sequencing was performed to analyze the antimicrobial resistance genes,multilocus sequence typ-ing,and plasmid types.The sequencing data were used to construct a phylogenetic tree based on core genome single-nucleotide polymorphisms(cgSNPs).The isolates showed the highest resistance to ampicillin(87.1％),followed by tetracycline(79.2％)and nalidixic acid(64.4％).The resistance rate to cefotaxime was 38.6％.All 101 strains were classified into 60 STs,among which ST10,ST1491,and ST38 were dominant.Moreover,23 distinct plasmid replicons were identified,among which IncFIB was dominant.Diverse antimicrobial resistance genes(including quinolone,aminoglycoside,β-lactamase,and tetracycline)were identified.Insertion sequences(IS26,IS903B,and ISECP 1)were identified in upstream and downstream analysis of the gene context of the extended-spectrum β-lactamase bla CTX-M-14 and bla CTX-M-55 genes.In conclusion,multidrug resistant diarrhea-genic Escherichia coli isolated from clinical and food samples in Henan Province showed high genetic diversity and high antimi-crobial resistance.The dissemination of blaCTX-M carried by the strains was shown to be associated with the insertion sequence(IS).

Objective To analyze the prognostic significance and biological effects of cytochrome P450 family 27 subfamily A member 1(CYP27A1)in hepatocellular carcinoma(HCC),and to preliminarily explore its molecular mechanism of regulating the malignant growth of HCC.Methods The Cance Genome Atlas(TCGA)database was used to analyze the expression level of CYP27A1 and its prognostic effect on HCC patients.The samples were divided into CYP27A1 high-expression group(n=170)and low-expression group(n=170)based on the median expression of CYP27A1 in HCC,gene set enrichment analysis(GSEA)was performed to investigate gene sets associated with CYP27A1 expression.The subcellular localization of CYP27A1 was detected by immunofluorescence staining and search database.The over-expression plasmid of CYP27A1 was constructed and then transfected into the HCC cells MHCC-97H and HCCLM3 cell lines,including two groups,namely control group(transfecting empty vector)and CYP27A1 over-expression group(transfecting CYP27A1 over-expressed vector).CCK-8,flow cytometer,and reactive oxygen species(ROS)fluorescence probe were applied to detect the effects of CYP27A1 over-expression on cell viability,apoptosis and ROS levels in HCC cells.Combining bioinformatics to analyze the correlation between CYP27A1 and the expression of ROS generation-related genes and HCC proliferation-related genes.Results Compared with the normal liver tissue,the expression level of CYP27A1 mRNA in HCC tissue was significantly reduced(P<0.01).The expression of CYP27A1 was significantly correlated with sex,T stage,tumor grade and tumor stage of HCC patients(P<0.05).Compared to the CYP27A1 high-expression group,patients in CYP27A1 low-expression group had lower survival rate(P<0.01).GSEA enrichment analysis revealed that the levels of HCC stem cell-related gene clusters and HCC proliferation gene clusters were remarkably increased in CYP27A1 low-expression group.The immunofluorescence showed that CYP27A1 was mainly located in nucleus in MHCC-97H and HCCLM3,whereas CYP27A1 was mainly located in mitochondria in HepG2.CYP27A1 over-expression attenuated cell viability(P<0.01),and reduced the ROS levels(P<0.05),whereas it had no effects on the apoptosis in HCC cells(P>0.05).The expression of CYP27A1 and the expression of inhibiting ROS generation-related genes were positively correlated(P<0.05),while the expression of inhibiting ROS generation-related genes and the expression of HCC proliferation-related genes were negatively correlated(P<0.05).Conclusions The expression of CYP27A1 was decreased in HCC,and down-regulated CYP27A1 promoted cell growth by enhancing ROS generation,although the precise mechanism requires future educidation.

Objective To summarize the treatment of cervical cancer patients diagnosed before 34 weeks of gestation who chose to continue pregnancy,and to provide clinical experience for improving maternal and fetal outcomes.Methods Clinical data of pregnant women with cervical cancer admitted to the Obstetrics and Gynecology Hospital,Fudan University from Jan 2013 to Feb 2024 were collected and analyzed.Treatment of patients diagnosed before 34 weeks of gestation and chose to continue pregnancy was summarized.Outcomes of patients and newborn were followed up.Results A total of 15 patients were enrolled with a median age of 34 years old.Nine cases(9/15)represented clinical symptom of abnormal vaginal bleeding,14 cases(14/15)of patients were diagnosed in the middle or late stages of pregnancy,12 cases(12/15)diagnosed with tumor size of more than 2 cm,13 patients(13/15)infected HPV type 16 or 18.The main pathological type was squamous cell carcinoma(9/15).Regarding therapy,one patient with stage Ⅰa1 was under observation and underwent a caesarean section and total hysterectomy at 35 weeks of gestation due to premature rupture of membrane and a scarred uterus.For the other patients with 14 stage Ⅰb,lymph node metastasis was excluded by pelvic lymphadenectomy or MRI,and then neoadjuvant chemotherapy was administered.Termination of pregnancy and standardized treatment for cervical cancer were provided after 34 weeks of gestation.One patient's pathology was upgraded to stage Ⅱa1 after surgery.Up to follow-up,13 out of 15 patients had survived without tumors.The average gestational age of newborns was(35.0±1.5)weeks,and the average birth weight was(2 345.33±431.44)g.Blood tests conducted one day after delivery of the newborns revealed that:8 newborns(8/15)had hypoleukocyte and one newborn(1/15)had anemia.After short-term hospitalization and supportive treatment,all newborns'progress was favorable.Conclusion For pregnant patients with stage Ⅰb cervical cancer diagnosed before 34 weeks of gestation,postponing termination to after 34 weeks of gestation through neoadjuvant chemotherapy and then giving standardized treatment for cervical cancer was safe with favorable maternal and fetal prognosis.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective To investigate the amplitude-integrated electroencephalography(aEEG)monitoring results of hospitalized neonates in plateau areas.Methods A retrospective analysis was conducted on 5 945 neonates who were admitted to the Department of Neonatology,Kunming Children's Hospital,and received aEEG monitoring from January 2020 to December 2022.According to the aEEG monitoring results,they were divided into a normal aEEG group and an abnormal aEEG group.The incidence rate of aEEG abnormalities was analyzed in neonates with various systemic diseases,as well as the manifestations of aEEG abnormalities and the consistency between aEEG abnormalities and clinical abnormalities.Results Among the 5 945 neonates,the aEEG abnormality rate was 19.28%(1 146/5 945),with an abnormality rate of 29.58%(906/3 063)in critically ill neonates and 8.33%(240/2 882)in non-critically ill neonates(P<0.05).The children with inherited metabolic diseases showed the highest aEEG abnormality rate of 60.77%(79/130),followed by those with central nervous system disorders[42.22%(76/180)]and preterm infants[35.53%(108/304)].Compared with the normal aEEG group,the abnormal aEEG group had significantly lower age and gestational age,as well as a significantly lower birth weight of preterm infants(P<0.05).Among the 1 146 neonates with aEEG abnormalities,the main types of aEEG abnormalities were sleep cycle disorders in 597 neonates(52.09%),background activity abnormalities in 294 neonates(25.65%),and epileptiform activity in 255 neonates(22.25%),and there were 902 neonates(78.71%)with abnormal clinical manifestations.The sensitivity and specificity of aEEG monitoring for brain function abnormalities were 33.51%and 92.50%,respectively.Conclusions In plateau areas,there is a relatively high rate of aEEG abnormalities among hospitalized neonates,particularly in critically ill neonates and those with smaller gestational ages and younger ages,suggesting a high risk of brain injury.Therefore,routine aEEG monitoring for the hospitalized neonates can help with the early detection of brain function abnormalities,the decision-making in treatment,and the formulation of brain protection strategies.