As one of the chronic diseases with high incidence in contemporary society, cervical spondylosis has increasing patient groups who gradually present a low age, and it seriously affects social and public health. Although modern medicine has made great progress in the pathological research and clinical treatment of cervical spondylosis, patients still face gastrointestinal side effects of nonsteroidal anti-inflammatory drugs(NSAIDs), neck pain, limited mobility, upper limb numbness, and other symptoms after conservative or surgical treatment. In the theory of traditional Chinese medicine(TCM), cervical spondylosis belongs to the categories of "Bi syndrome" "stiff neck" "stiff Bi", etc. With the change of the times, the change of lifestyle, and the application of western medicine treatment, the etiology and pathogenesis of TCM in cervical spondylosis also show new characteristics. In terms of etiology and pathogenesis, it involves the invasion of wind, cold, and dampness, long-term strain, liver and kidney deficiency, Qi and blood stasis, which are associated with factors such as cervical degeneration, muscle tension and spasm, intervertebral disc herniation, and nerve root compression in modern medicine. In terms of the evolution of pathogenesis, in the early stage, wind, cold, and dampness, were more common in Xuanfu, resulting in unfavorable muscles and bones, poor flow of Qi and blood, and cervical spondylosis and radiculopathy. Medium-term phlegm stasis and internal knots, sluggish muscles and veins, and long-term weathering and fire are more likely to occur in the vertebral artery and sympathetic radiculopathy. In the later stage, the positive Qi is depleted; the true Yin is damaged, and the viscera Qi and blood are deficient, which is most common in cervical myelopathy. The strategy of treating cervical spondylosis with TCM classic formulas applies Gegen Decoction, Wutou Decoction, Qianghuo Shengshi Decoction, Mahuang Jiazhu Decoction to patients with wind, cold, and dampness. Patients with phlegm dampness and blood stasis are treated with Huoxue Xiaoling Dan, Jinlingzi Powder, Siwu Decoction, Banxia Baizhu Tianma Decoction, Shuanghe Decoction, etc. For those patients with liver, spleen, and kidney deficiency, Huangqi Guizhi Wuwu Decoction, Tianma Gouteng Decoction, Guishao Dihuang Pills, Shenling Baizhu Powder, and Lizhong Decoction are used to invigorate the spleen, nourish Qi and blood, and tonify liver and kidney. In clinical practice, the authors advocate a safe and effective treatment plan of classic formulas based on deficiency and excess, the integration of formulas and syndromes, and the combination of modern research results, so as to relieve symptoms, reduce recurrence, and reduce medical burden.
Humans ; Spondylosis/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Cervical Vertebrae/pathology*

OBJECTIVES: To study the clinical and genetic characteristics of osteopetrosis (OPT) in children. METHODS: A retrospective analysis was performed on the clinical data of 14 children with OPT. Whole-exome sequencing was used to detect pathogenic genes, and clinical phenotypes and genotypic features were summarized. RESULTS: Among the 14 children (10 males and 4 females), the median age at diagnosis was 8 months. Clinical manifestations included systemic osteosclerosis (14 cases, 100%), anemia (12 cases, 86%), infections (10 cases, 71%), thrombocytopenia (9 cases, 64%), hepatosplenomegaly (8 cases, 57%), and developmental delay (5 cases, 36%). Malignant osteopetrosis (MOP) cases had lower platelet counts, creatine kinase isoenzyme, and serum calcium levels, but higher white blood cell counts, lactate dehydrogenase, and alkaline phosphatase levels compared to non-MOP cases (P<0.05). Genetic testing identified 15 variants in 12 patients, including 8 variants in the CLCN7 gene (53%), 6 in the TCIRG1 gene (40%), and 1 in the TNFRSF11A gene (7%). Three novel CLCN7 variants were identified: c.2351G>C, c.1215-43C>T, and c.1534G>A. All four patients with TCIRG1 variants exhibited MOP clinical phenotypes. Of the seven patients with CLCN7 variants, 4 presented with intermediate OPT, 2 with benign OPT, and 1 with MOP. CONCLUSIONS Clinical phenotypes of OPT in children are heterogeneous, predominantly involving CLCN7 and TCIRG1 gene variants, with a correlation between clinical phenotypes and genotypes.
Humans ; Osteopetrosis/genetics* ; Male ; Female ; Infant ; Child, Preschool ; Retrospective Studies ; Vacuolar Proton-Translocating ATPases/genetics* ; Child ; Chloride Channels/genetics* ; Mutation ; Receptor Activator of Nuclear Factor-kappa B

OBJECTIVE: To analyze two families with inherited dysfibrinogenemia, and explore the molecular pathogenic mechanisms. METHODS: The coagulation indexes of the probands and their family members were detected. The FGA, FGB, and FGG exons and their flanking sequences were amplified by PCR, and the mutation sites were identified by sequencing. SIFT, PolyPhen2, LRT, ReVe, MutationTaster, phyloP, and phastCons bioinformatics software were used to predict the functional impact of the mutation sites. Protein structure and amino acid conservation analysis of the variant were conducted using PyMOL and Clustal X software. RESULTS: The thrombin time (TT) of the proband in family 1 was prolonged to 37.00 s, and Fg∶C decreased to 0.52 g/L. The TT of the proband in family 2 was 20.30 s, and Fg∶C was 1.00 g/L, which was lower than the normal range. Genetic analysis revealed that the proband in family 1 had a heterozygous mutation c.80T>C in FGA, resulting in the substitution of phenylalanine 27 with serine (Phe27Ser). The proband in family 2 had a heterozygous mutation c.1007T>A in FGG, resulting in the substitution of methionine 336 with lysine (Met336Lys). Bioinformatics software prediction analysis indicated that both mutations were deleterious variants. PyMOL mutation models revealed that the Aα chain mutation (Phe27Ser) in family 1 and γ chain mutation (Met336Lys) in family 2 resulted in alterations in spatial structure and reduced protein stability. Clustal X results showed that both Aα Phe27 and γMet336 were highly conserved across homologous species. CONCLUSION Heterozygous mutations of FGA gene c.80T>C and FGG gene c.1007T>A are both pathogenic variants, causing inherited dysfibrinogenemia.
Female ; Humans ; Male ; Afibrinogenemia/genetics* ; Fibrinogen/genetics* ; Heterozygote ; Mutation ; Pedigree

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Objective:To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage ⅠA lung adenocarcinoma patients.Methods:A retrospective analysis was conducted on 63 clinical stage ⅠA lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis.Results:After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations ( HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations ( HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations ( HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations ( HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations ( HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage ⅠA lung adenocarcinoma patients. Conclusions:PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage ⅠA lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.

Objective:To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage ⅠA lung adenocarcinoma patients.Methods:A retrospective analysis was conducted on 63 clinical stage ⅠA lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis.Results:After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations ( HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations ( HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations ( HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations ( HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations ( HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage ⅠA lung adenocarcinoma patients. Conclusions:PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage ⅠA lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.