Objective To analyze the clinical manifestations and genetic etiology of three families with hereditary spastic paraplegia(HSP).Methods Gene analysis was performed on patients of the three HSP families from the Gansu Provincial Maternity and Child-care Hospital.Results The proband of family 1 was autosomal recessive spastic paraplegia type 35 caused by homozygous variant c.159_176delGGCGGGCCAGGACATCAG(p.Arg53_Ser59delinsSer)in FA2H.The proband in family 2 was autosomal recessive spastic paraplegia type 47 caused by homozygous variant c.1399G>T(p.Glu467Ter)in AP4B1,and the proband in family 3 was autosomal recessive spastic paraplegia type 11 caused by homozygous variation c.7023C>G(p.Tyr2341Ter)in SPG11.Among them,the variant c.1399G>T(p.Glu467Ter)of AP4B1 is a novel variant,that has not been reported before,according to the ACMG guidelines,the pathogenicity of this variant is pathogenic.Conclusion This study has expanded the variant spectrum of AP4B1 which provides basic data to improve clinical understanding and diagnostic capabilities of HSP patients.

Objective:To evaluate the quality of psychological distress assessment tools for cancer patients and provide evidence for clinical nurses in selecting appropriate instruments.Methods:A systematic literature search was conducted in China National Knowledge Infrastructure, VIP, Wanfang Data, China Biology Medicine disc, Embase, Cochrane Library, Medline, Web of Science, and PubMed from database inception to May 27, 2024, to identify studies on psychological distress assessment tools for cancer patients. Two reviewers independently screened the literature and extracted data based on inclusion and exclusion criteria. The quality of the included tools was evaluated using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guideline, and the quality grading was made using a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.Results:A total of 25 articles involving 21 assessment tools were included. None of the tools reported measurement error, responsiveness, or hypothesis testing. Among them, 3 instruments: Chinese version of the Cancer Distress Scales for Adolescent and Young Adults (CDS-AYA-C), Chinese version of the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), and the Chinese version of the Short Demoralization Scale (DS-Ⅱ-C) were given grade A recommendations. The remaining 18 tools received grade B recommendations.Conclusions:The CDS-AYA-C, MAX-PC, and DS-Ⅱ-C demonstrated relatively balanced measurement properties and can be temporarily recommended for assessing psychological distress in cancer patients. However, further validation of their methodological quality and psychometric properties is needed. It is also recommended to develop culturally adapted psychological distress assessment tools for cancer patients in China.

Objective:To analyze the status of registration of clinical trials of radiopharmaceuticals in China, and to provide reference for the development and clinical application of radiopharmaceuticals.Methods:By searching the clinical trial registration and information disclosure platform of the Center for Drug Evaluation of the National Medical Products Administration (NMPA), the data on clinical trials of radiopharmaceuticals registered from 2014 to 2024 were collected and analyzed for trial design, administered dose, common indications, and geographical distribution.Results:A total of 77 clinical trials were included. The Compound Annual Growth Rate for the number of projects from 2014 to 2024 was 40%. Diagnostic radiopharmaceuticals were predominantly based on 18F and 99Tc m, while therapeutic radiopharmaceuticals primarily utilized 177Lu and 90Y. All indications were concentrated in the field of oncology. Regarding trial design, non-randomized (71.4%), open-label (89.6%), and single-arm (66.2%) trials accounted for the highest proportions. Geographical distribution showed Beijing (29 trials), Shanghai (18 trials), and Jiangsu province (14 trials) as the regions with the highest concentration of clinical trials. Conclusions:Radiopharmaceutical clinical trials in China have shown rapid growth. However, research remains predominantly focused on oncology, with a relatively high proportion of early-stage trials. In order to fully utilize the potentials of radiopharmaceuticals and improve the quality of clinical trials, nuclear medicine researches should broaden therapeutic applications, implement prudently administerd dose in clinical trials, and implement optimized radiation protection procedures across all clinical trial centers.

Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

The chemical constituents from Cephalotaxus lanceolata were isolated and purified by using multiple chromatographic techniques, including octadecylsilane(ODS), silica gel, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography(HPLC). A total of 17 compounds obtained were identified by using spectroscopic methods such as nuclear magnetic resonance(NMR), mass spectrometry(MS), and ultraviolet(UV) combined with literature data. Compound 1 was a new alkaloid dimer, named cephalancetine E. The known compounds were determined as cephalancetine A(2), 11-hydroxycephalotaxine(3), 4-hydroxycephalotaxine(4), cephalotaxine(5), epicephalotaxine(6), cephalotaxine β-N-oxide(7), acetylcephalotaxine(8), cephalotine A(9), cephalotine B(10), 11-hydroxycephalotaxine hemiketal(11), 3-deoxy-3,11-epoxy-cephalotaxine(12), cephalotaxinone(13), isocephalotaxinone(14), 2,11-epoxy-1,2-dihydro-8-oxo-cephalotaxine(15), cephalotaxamide(16), and drupacine(17), respectively. Compounds 11, 12, and 15 were isolated from the Cephalotaxus genus for the first time. The biological activity was tested for compounds 1-17. The results reveal that compound 17 displays potent inhibitory activities against three human cancer cell lines(HepG-2, MCF-7, and SH-SY5Y).
Cephalotaxus/chemistry* ; Humans ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology* ; Harringtonines/pharmacology* ; Molecular Structure ; Dimerization ; Alkaloids/isolation & purification* ; Magnetic Resonance Spectroscopy

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

Objective:To analyze the status of registration of clinical trials of radiopharmaceuticals in China, and to provide reference for the development and clinical application of radiopharmaceuticals.Methods:By searching the clinical trial registration and information disclosure platform of the Center for Drug Evaluation of the National Medical Products Administration (NMPA), the data on clinical trials of radiopharmaceuticals registered from 2014 to 2024 were collected and analyzed for trial design, administered dose, common indications, and geographical distribution.Results:A total of 77 clinical trials were included. The Compound Annual Growth Rate for the number of projects from 2014 to 2024 was 40%. Diagnostic radiopharmaceuticals were predominantly based on 18F and 99Tc m, while therapeutic radiopharmaceuticals primarily utilized 177Lu and 90Y. All indications were concentrated in the field of oncology. Regarding trial design, non-randomized (71.4%), open-label (89.6%), and single-arm (66.2%) trials accounted for the highest proportions. Geographical distribution showed Beijing (29 trials), Shanghai (18 trials), and Jiangsu province (14 trials) as the regions with the highest concentration of clinical trials. Conclusions:Radiopharmaceutical clinical trials in China have shown rapid growth. However, research remains predominantly focused on oncology, with a relatively high proportion of early-stage trials. In order to fully utilize the potentials of radiopharmaceuticals and improve the quality of clinical trials, nuclear medicine researches should broaden therapeutic applications, implement prudently administerd dose in clinical trials, and implement optimized radiation protection procedures across all clinical trial centers.