ObjectiveTo investigate the liver histopathological features of HBeAg-negative patients in the indeterminate phase of low-viral-load chronic hepatitis B virus （HBV） infection. MethodsA total of 271 patients with low-viral-load HBeAg-negative chronic HBV infection who underwent liver biopsy in Department of Infectious Diseases， Affiliated Hospital of Yan’an University， from September 2013 to June 2021 were enrolled as subjects， and the degree of liver injury was compared between patients based on age， sex， presence or absence of the family history of hepatitis B， HBsAg， and alanine aminotransferase （ALT） level. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 271 patients with HBeAg-negative chronic HBV infection， 86 patients （31.73%） grade≥A2 liver inflammatory activity， 72 （26.57%） had a liver fibrosis stage of ive， and 112 （41.33%） had moderate or severe liver histological injury. The proportion of patients with grade≥A2 liver inflammatory activity in the patients with ALT>20 U/L was significantly higher than that in the patients with ALT≤20 U/L （χ²=3.938， P=0.047）. There were no significant differences in the proportion of patients with grade≥A2 liver inflammatory activity between the patients with different ages， sexes， family history of hepatitis B， HBsAg levels （all P>0.05），there were no significant differences in the proportion of patients with a liver fibrosis stage of ≥F2 between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）， and the stratified analysis of patients aged≤30 years and patients without the family history of hepatitis B showed no statistical significance between groups （all P>0.05）. There was no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）. ConclusionSignificant liver injury is observed in more than 40% of the patients with low-viral-load HBeAg-negative chronic HBV infection， and there is no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels. Even for the patients aged≤30 years who deny the family history of hepatitis B， there is still a considerable proportion of patients with liver injury， which should be taken seriously by clinicians.

To determine the optimal cultivation duration and harvest period for cultivated Notopterygium incisum and promote its industrial development, this study established a characteristic chromatographic profile of cultivated N. incisum and employed chemometrics combined with entropy-weighted grey correlation analysis to assess differences in agronomic traits and quality indicators across different cultivation years and harvest periods. By comparing with reference substances, ten common peaks were identified, including chlorogenic acid, p-coumaric acid, ferulic acid, marmesinin, nodakenin, isochlorogenic acid B, notopterol, phenethyl ferulate, isoimperatorin, and falcarindiol. The similarity between the characteristic chromatographic profiles of N. incisum at different cultivation years and the reference profile was all above 0.932. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) revealed that the quality of 1-to 3-year-old cultivated N. incisum was highly dispersed and unstable, whereas the quality of 4-year-old cultivated N. incisum remained relatively stable across different harvest periods. This suggests that the accumulation of relevant compounds in the medicinal material had reached a plateau, confirming that the optimal cultivation period for N. incisum is four years. Entropy-weighted grey correlation analysis indicated that the quality of 4-year-old cultivated N. incisum across different harvest periods ranked from highest to lowest as follows: November, December, October, August, July, and September, demonstrating that November is the optimal harvest time. The findings of this study establish the suitable cultivation duration and optimal harvest period for N. incisum, providing a scientific basis for cultivation guidance and quality standardization.
Chromatography, High Pressure Liquid/methods* ; Apiaceae/chemistry* ; Entropy ; Chemometrics/methods* ; Drugs, Chinese Herbal/chemistry* ; Principal Component Analysis ; Quality Control

As a member of the Citrus genus of the Rutaceae family, Citrus changshan-huyou(CSHY) is mainly produced in Quzhou city, Zhejiang province. Modern research shows that different medicinal parts of CSHY(immature fruit, mature fruit peel, flower buds, leaves, seeds, etc.) are abundant in flavonoids, terpenes, coumarins, phenolic acids, and volatile oils. Their pharmacological activities include respiratory system protection, liver protection, anti-inflammation, anti-hyperlipidemia, anti-hyperglycemia, and antioxidation. Based on the summarization of 374 chemical components in different medicinal parts of CSHY identified in the past 20 years, this study reviewed their pharmacological actions and mechanisms and further analyzed the current status of quality control of different medicinal parts of CSHY, aiming to provide reference for the resource development and exploitation and the quality control research of different medicinal parts of CSHY.
Citrus/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Plants, Medicinal/chemistry* ; Quality Control ; Animals

OBJECTIVE: To compare clinical efficacy of transaxillary posterior margin approach and translateral margin approach for the treatment of Miller typeⅡand Ⅳ scapular fractures. METHODS: From June 2020 to June 2024, 28 patients with fresh scapular fractures (Miller typeⅡand Ⅳ) who were treated with open reduction and locked plate internal fixation were retrospectively analyzed and divided into two groups. There were 13 patients in posterior axillary margin group, including 8 males and 5 females, aged from 26 to 71 years old with an average of (39.2±6.5) years old;5 patients with typeⅡand 8 patients with type Ⅳ according to Miller classification;9 patients caused by falling down, 4 patients caused by car accident;7 patients on the right side, 6 patients on the left side;the time from injury to operation ranged from 3 to 5 days with an average of (4.07±0.86) days. There were 15 patients in lateral scapula margin group, including 10 males and 5 females, aged from 27 to 63 years old with an average of (43.6±8.5) years old;7 patients with typeⅡand 8 patients with type Ⅳ according to Miller classification;10 patients caused by falling down, 5 patients caused by car accident;6 patients on the right side, 9 patients on the left side;the time from injury to operation ranged from 3 to 5 days with an average of (4.20±0.67) days. Operative time, intraoperative blood loss, fracture healing time, glenopolar angle (GPA) immediately after operation were compared between two groups. Visual analogue scale (VAS) and Constant-Murley shoulder joint function score were used to evaluate clinical effect at 3 and 6 months after operation, respectively, and the joint motions were evaluated at 6 months after operation. RESULTS: None of patients occurred wound infection, vascular and nerve damage, loosening or rupture of internal fixation. Both groups were followed up for 8 to 12 months with an average of (9.6±1.5) months. Operative time and intraoperative blood loss of posterior axillary margin group were (76.92±5.60) min and (84.86±10.08) ml, respectively, which were better than those of lateral scapula margin group(84.67±6.93) min and(115.00±12.39) ml(P<0.05). Immediate GPA in posterior axillary margin group (36.62±0.87) °and lateral scapula margin group (36.20±0.82)°were significantly improved compared with preoperative (16.10±1.14) °, (16.20±1.20) °(P<0.05), while there was no statistical significance between two groups (P>0.05). There were no significant difference in fracture healing time and postoperative VAS at 3 and 6 months between two groups (P>0.05). Postoperative Constant-Murley score of posterior axillary margin group (75.00±4.02) was higher than that of lateral scapular margin group (70.86±4.24) at 3 months (P<0.05), while there was no significant difference between two groups at 6 months after operation (P>0.05). At 6 months after operation, joint motion of posterior axillary margin group in flexion (160.38±13.61)°, abduction (154.61±13.91)°, rotation (83.08±2.53)°, rotation (62.69±2.59) ° and extension (51.54±3.15) °, respectively, which were higher than that of lateral scapular margin group in (148.00±15.44)°, (144.00±11.05)°, (79.67±3.99)°, (57.33±4.95)°, (47.33±4.16)°(P<0.05). CONCLUSION Compared with lateral margin of scapula intermuscular space approach, Buttress approach through the posterior axillary margin for the treatment of Miller typeⅡand Ⅳ scapular fractures provides extensive intraoperative visual field exposure, stable fracture support and less surgical trauma, which could shorten operative time and reduce intraoperative blood loss, providing a new reference for the treatment of complex scapular fractures.
Humans ; Male ; Female ; Middle Aged ; Scapula/surgery* ; Adult ; Aged ; Fractures, Bone/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; Axilla/surgery*

OBJECTIVE: To screen out the key metabolites related to diabetic foot (DF) by integrating genome-wide association studies (GWAS) and metabolome genome-wide association studies (mGWAS). METHODS: The literature databases such as PubMed and China national knowledge infrastructure(CNKI), as well as genomics databases such as PAN UKBB, FinnGen, and IEU Open GWAS were systematically retrieved from database estobilishment to November 2024 on DF-related single nucleotide polymorphisms and genome-wide association studies. DF-single nucleotide polymorphism-metabolite network was constructed by mGWAS package and mGWAS-Explorer platform. The causal relationship between key factors was evaluated by two-sample Mendelian randomization. The genetic correlation between DF and 575 metabolites (source:IEU Open GWAS) was evaluated by linkage disequilibrium score regression. In vitro experiments were conducted to induce injury of human umbilical vein endothelial cells with 30 mM glucose and intervene with 20 μM γ-tocopherol. Changes in cell migration, scratch healing and tube formation function were detected. RESULTS: Twenty-senen literatures on single nucleotide polymorphism literatures and 3 studies on GWAS were included. Genetic analysis results showed DF-related single nucleotide polymorphisms were enriched in vascular endothelial dysfunction-related pathways (such as fluid shear stress and atherosclerosis). The results of metabolic network analysis screened out 19 associated metabolites, among which 12 such as γ -tocopherol and pyruvate had significant genetic correlations with DF. Mendelian randomization suggested matrix metalloproteinase-9(MMP-9) might be a potential driver of DF (β=0.658, P=0.063 8), and the occurrence of DF could reduce the level of high-density lipoprotein (β=-0.002, P=0.015 2). The results of in vitro experiments confirmed that γ -tocopherol could improve endothelial dysfunction induced by high glucose, specifically manifested as an increase in the number of cell migrations, improvement in the scratch healing rate, and recovery of tubule formation ability (P<0.05). CONCLUSION DF has a genetic basis centered on vascular endothelial dysfunction, and its occurrence can lead to further metabolic disorders. The key single nucleotide polymorphism loci integrated provided molecular markers for the risk stratification of foot ulcers in diabetic patients. In addition, γ -tocopherol has demonstrated clinical application potential as a therapeutic drug for DF by significantly improving the function of vascular endothelial cells in a high-glucose environment.
Humans ; Diabetic Foot/drug therapy* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Genomics ; Metabolomics ; Metabolome

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms. Testosterone, as one of the most critical sex hormones, is essential for the development of the reproductive system, maintenance of reproductive function, and the overall health of males. The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes. Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis. We also examined the specific effects of these genes on the occurrence, development, and treatment of common male diseases, including late-onset hypogonadism, erectile dysfunction, male infertility, and prostate cancer.
Testosterone/metabolism* ; Humans ; Male ; Circadian Clocks/genetics* ; Circadian Rhythm Signaling Peptides and Proteins/metabolism* ; Circadian Rhythm/physiology* ; Hypogonadism/metabolism* ; Erectile Dysfunction/metabolism* ; Infertility, Male/metabolism* ; Prostatic Neoplasms/metabolism* ; Men's Health

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female

Children with bronchopulmonary dysplasia (BPD) often exhibit severe respiratory problems and significant pulmonary dysfunction during school age and adulthood. Exercise tests show a decline in cardiopulmonary function and physical performance in children with BPD, who also have a higher incidence of pulmonary hypertension. These children generally perform poorly in terms of intelligence, language, and motor development. As they age, the risk of neurodevelopmental disorders increases, and health-related quality of life is also affected. This article reviews the prognosis of the respiratory system, physical capacity, cardiovascular system, nervous system, and health-related quality of life in children with BPD, aiming to improve the management of these patients and enhance their subsequent quality of life.
Humans ; Bronchopulmonary Dysplasia/complications* ; Prognosis ; Quality of Life ; Child

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