Objective To introduce the causes of accidents and the diagnosis and treatment of two patients with radiation-induced skin injury admitted to our hospital in 2023, and to provide a reference for the clinical treatment of subsequent radiation-induced skin injury. Methods The clinical treatment process of two patients with acute skin injury caused by external radiation exposure were summarized and analyzed. Results The exposure history of the two patients was reconstructed, the flaw detection scenario was simulated, the biological dose and hand skin exposure dose were estimated, and the infrared thermal imaging device was used for dynamic monitoring. A comprehensive analysis was conducted based on clinical manifestations and other data. The diagnosis of “Xie” was excessive exposure combined with acute radiation-induced skin injury on both hands (Grade IV for the right hand palm, index finger, and middle finger and Grade II for the left hand little finger). The diagnosis of “Hao” was acute radiation-induced skin injury on both hands (Grade I). The two patients received different clinical treatment measures: “Xie” was treated with both local and systemic therapies, while “Hao” was mainly treated with systemic therapy. Conclusion After systematic and effective treatment, the radiation-induced skin injuries healed in both patients.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

ObjectiveTo investigate the material basis and mechanism of action of Tuoli Xiaodu San in treating ulcerative colitis （UC） by integrating transcriptomics， network pharmacology， and experimental validation. MethodsNetwork pharmacology was initially employed to screen the active components and potential mechanisms of Tuoli Xiaodu San for treating UC. A UC mouse model was established by dextran sulfate sodium （DSS） induction. The mice were divided into the following groups： normal， model， high-dose （11.3 g·kg^-1） Tuoli Xiaodu San， low-dose （5.7 g·kg^-1） Tuoli Xiaodu San， and positive control （mesalazine， 0.4 g·kg^-1）. Intragastric administration commenced on day 1 of modeling and continued for 7 consecutive days. The disease activity index （DAI） was assessed daily. Hematoxylin-eosin （HE） staining was used to observe colonic pathological changes. Serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1 beta （IL-1β） and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay （ELISA）. Transcriptome sequencing was performed on mouse colonic tissues， and the results were integrated with network pharmacology findings for in-depth analysis of Tuoli Xiaodu San's potential mechanisms in treating UC. Finally， the expression of key genes and proteins in the identified signaling pathways were detected using Western blot and Real-time polymerase chain reaction （Real-time PCR）. ResultsThe combined analysis of network pharmacology and transcriptomics results showed that the multi-pathway network with phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway as its core was the key mechanism of Tuoli Xiaodu San in the treatment of UC. Tuoli Xiaodu San administration significantly ameliorated weight loss， diarrhea， and bloody stools in UC mice， reduced the DAI scores （P<0.05， P<0.01）， lowered the colonic histopathological scores （P<0.01）， alleviated colon shortening （P<0.01）， and downregulated serum levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）. Molecular biology experiments confirmed that Tuoli Xiaodu San significantly inhibited the mRNA and protein expression， as well as the phosphorylation levels， of PI3K， Akt， and p65 in colonic tissues （P<0.05， P<0.01）. ConclusionTuoli Xiaodu San can regulate the multi-pathway network with PI3K/Akt as its core through multi-component synergy， thereby reducing colonic inflammatory damage and exerting a therapeutic effect on UC.

Objective To investigate the prevalence of Paragonimus infection in freshwater crabs from selected areas of Yunnan Province, and to perform molecular characterization and phylogenetic analysis of the isolated parasites based on the internal transcribed spacer 2 (ITS2) and cytochrome c oxidase subunit I (COI) gene sequences. Methods Freshwater crabs were collected from both local markets and natural streams in Zhaotong City, Pu’er City, Dehong Dai and Jingpo Autonomous Prefecture, Baoshan City, Honghe Hani and Yi Autonomous Prefecture and Lincang City of Yunnan Province from May to August 2025. Paragonimus metacercariae were isolated using a sieve and sedimentation method. After morphological identification of the metacercariae, the infection rate and infection intensity of Paragonimus in freshwater crabs were calculated. Then genomic DNA was extracted from an individual metacercaria, and ITS2 and COI gene fragments were amplified using a PCR assay and sequenced. The obtained sequences were aligned with those available in the GenBank database. Genetic distances were calculated with the software MEGA 11.0 based on the Kimura 2-parameter model, and phylogenetic trees were built using the neighbour-joining method. Results A total of 600 freshwater crabs were collected, with 18 positive for Paragonimus metacercariae. The prevalence of Paragonimus infection was 12.00% (18/150) in freshwater crabs from Zhaotong City, while no Paragonimus infection was detected in crabs from other five prefectures (cities). Twenty metacercariae were recovered, with an overall infection intensity of 1.11 metacercariae per crab. Morphological observation revealed two types of Paragonimus metacercariae, including 19 resembling P. skrjabini, and 1 resembling P. paishuihoensis. Ten metacercariae of distinct morphotypes were randomly selected for molecular identification, and sequence alignment and phylogenetic analysis of ITS2 and COI genes identified 9 as P. skrjabini and 1 as P. paishuihoensis. The nine ITS2 gene sequences shared 98.34% to 100.00% homology with the reference sequence of P. skrjabini (GenBank accession number: KX129924.1), and the single ITS2 gene sequence showed 100.00% homology with the reference sequence of P. paishuihoensis (GenBank accession number: OM401939.1), while its COI sequence showed 98.80% homology with the reference sequence of P. paishuihoensis (GenBank accession number: AB679288.1). Phylogenetic analysis further confirmed that the 10 sequences were clustered separately into the clades of P. skrjabini and P. paishuihoensis. Conclusions This study reports the first detection of P. paishuihoensis in freshwater crabs from Zhaotong City, Yunnan Province, and confirms P. skrjabini as the dominant Paragonimus species in this region. Molecular identification and phylogenetic analysis based on ITS2 and COI genes are effective to distinguish Paragonimus species, which provides the scientific evidence for precise control of paragonimiasis in Yunan Province.

Objective: To investigate the incidence and independent risk factors of adverse events (AEs) associated with therapeutic plasma exchange (TPE) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to provide evidence to support the safe use of TPE in clinical practice. Methods: This retrospective study included 167 allo-HSCT recipients who underwent a total of 385 TPE procedures between March 2022 and December 2023. Patients were divided into two groups according to the occurrence of TPE-related AEs. Baseline characteristics, plasma exchange parameters, and clinical features were collected. Univariate analysis and multivariable Firth logistic regression were performed to identify independent risk factors for AEs. Results: A total of 385 TPE procedures were performed in 167 allo-HSCT patients, and 33 patients (19.8%) experienced TPE-related AEs. Among the 33 patients who experienced AEs, allergic reactions were the most common (n=18, 54.5%), followed by blood pressure fluctuations (n=11, 33.3%) and hypocalcemia (n=4, 12.1%). Most AEs were classified as grade II (n=23, 69.7%), and no grade IV (fatal) events were observed. Univariate analysis demonstrated a significant difference in the incidence of AEs among different hematocrit (HCT) categories (<20%, 20%-30%, and>30%) (Fisher's exact test, P=0.022). Although the overall difference was statistically significant, none of the pairwise comparisons remained significant after Bonferroni correction (adjusted P>0.0167). Multivariable Firth logistic regression identified higher HCT levels, analyzed as a continuous variable (OR=1.07, 95% CI: 1.01-1.13, P=0.020), and TPE performed for cytokine release syndrome (CRS) (OR=9.21, 95% CI: 1.25-78.00, P=0.030) as potential independent risk factors for TPE-related AEs. Receiver operating characteristic (ROC) curve analysis showed that HCT had an AUC of 0.67 (95% CI: 0.57-0.77) for predicting AEs, with an optimal cutoff value of 24.5%, a sensitivity of 60.6%, and a specificity of 75.4%. Using this cutoff, the AEs rate was significantly higher in patients with HCT≥24.5% than in those with HCT<24.5% (37.7% vs 11.4%, P<0.001). Conclusion: A-mong allo-HSCT patients receiving TPE, allergic reactions were the predominant AEs. Higher HCT levels and TPE performed for CRS may be associated with an increased risk of AEs. HCT≥24.5% may help identify patients requiring intensified monitoring, although its discriminatory ability is moderate (AUC=0.67) and it should not be used as a standalone criterion for clinical decision-making. Findings regarding the CRS subgroup require validation in larger cohorts. Optimizing extracorporeal circuit priming and strengthening peri-procedural monitoring may help improve the safety of TPE.

ObjectiveTo investigate the mechanism by which Bushao Tiaozhi capsules （BSTZ） ameliorate hyperlipidemia based on untargeted metabolomics and targeted bile acid quantification. MethodsA rat model of hyperlipidemia was established with a high-fat diet. The rats were randomized into five groups： normal control， model， atorvastatin calcium （1.8 mg·kg^-1）， and low-dose （2.88 g·kg^-1） and high-dose （5.76 g·kg^-1） BSTZ groups. All treatments were administered for four consecutive weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by biochemical assays. Hepatic histopathological changes were evaluated via hematoxylin-eosin （HE） staining， and lipid droplet deposition was assessed by oil red O staining. Integrated untargeted metabolomics and targeted bile acid quantification were employed to investigate BSTZ-induced alterations in hepatic metabolic profile and bile acid profile. Additionally， correlation analyses were conducted between differential bile acids and lipid parameters to identify key bile acids. ResultsCompared with the normal control group， the model group exhibited elevated serum TC， TG， and LDL-C levels （P<0.01） and a reduced HDL-C level （P<0.01）， along with marked hepatic steatosis and extensive lipid droplet deposition. Compared with the model group， all BSTZ treatment groups showed decreased TC， TG， and LDL-C levels （P<0.01） and increased HDL-C levels （P<0.01）， accompanied by notably alleviated hepatic steatosis and lipid deposition. Untargeted metabolomics and targeted bile acid quantification revealed that BSTZ significantly remodeled the hepatic bile acid profile， characterized by elevated levels of secondary bile acids （DCA， HDCA， TDCA， and TLCA） and reduced levels of primary bile acids （CDCA and TCDCA）. Correlation analyses further demonstrated strong associations between differential bile acids and lipid parameters： elevated secondary bile acids were negatively correlated with serum TC， TG， and LDL-C levels， whereas primary bile acids were positively correlated with these parameters. ConclusionBSTZ can ameliorate dyslipidemia and hepatic lipid accumulation in hyperlipidemic rats by regulating hepatic bile acid homeostasis， which provides metabolic clues for subsequent mechanism validation.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

Purpose: This study aimed to evaluate the contrast-enhanced ultrasound with Sonazoid (Sonazoid-CEUS) features of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: In this retrospective study, patients who underwent surgical resection and were histopathologically diagnosed with NAFLD or cirrhosis-related HCC were included. All patients received Sonazoid-CEUS examinations within 1 week prior to hepatic surgery. The enhancement patterns of HCC lesions were evaluated and compared between the two groups according to the current World Federation for Ultrasound in Medicine and Biology guidelines. Multivariate logistic regression analysis was used to assess the correlations between Sonazoid-CEUS enhancement patterns and clinicopathologic characteristics. Results: From March 2022 to April 2023, a total of 151 patients with HCC were included, comprising 72 with NAFLD-related HCC and 79 with hepatitis B virus (HBV) cirrhosis–related HCC. On Sonazoid-CEUS, more than half of the NAFLD-related HCCs exhibited relatively early and mild washout within 60 seconds (54.2%, 39/72), whereas most HBV cirrhosis–related HCCs displayed washout between 60 and 120 seconds (46.8%, 37/79) or after 120 seconds (39.2%, 31/79) (P<0.001). In the patients with NAFLD-related HCC, multivariate analysis revealed that international normalized ratio (odds ratio [OR], 0.002; 95% confidence interval [CI], 0.000 to 0.899; P=0.046) and poor tumor differentiation (OR, 21.930; 95% CI, 1.960 to 245.319; P=0.012) were significantly associated with washout occurring within 60 seconds. Conclusion Characteristic Sonazoid-CEUS features are useful for diagnosing HCC in patients with NAFLD.

Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.