Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional’s skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.

Background Coal workers' pneumoconiosis is a serious occupational disease in China. Exhaled volatile organic compounds (VOCs) can serve as the "breath fingerprint" of internal pathological processes, which provides a theoretical basis for exhaled VOCs to be used as potential non-invasive biomarkers for early diagnosis of coal workers' pneumoconiosis. Objective To screen out the characteristic VOCs and important characteristic VOCs of exhaled air in patients with coal workers' pneumoconiosis, and to explore the potential of these VOCs as biomarkers for early non-invasive diagnosis of the disease. Methods In this study, 27 VOCs in the exhaled breath of 22 patients with stage I coal workers' pneumoconiosis, 77 workers exposed to dust, and 92 healthy controls were quantitatively detected by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Substances with P<0.05 in univariate analysis and variable importance projection (VIP) >1 in supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model were selected as the characteristic VOCs for early diagnosis of coal workers' pneumoconiosis. Age was included in the LASSO regression model as a covariate to screen out important characteristic VOCs, and the diagnostic performance was evaluated by receiver operating characteristic (ROC) curve. Spearman correlation was further used to explore the correlation between important characteristic VOCs and clinical lung function indicators. Results Through univariate analysis and OPLS-DA modeling, 8 VOCs were selected, including 2-methylpentane, 3-methylpentane, n-hexane, methylcyclopentane, n-heptane, methylcyclohexane, 4-methyl-2-pentanone, and 2-hexanone, in exhaled breath of patients with coal workers' pneumoconiosis. The concentrations of 4 VOCs, including 3-methylpentane, n-hexane, 4-methyl-2-pentanone, and 2-hexanone, showed a decreasing trend with the increase of dust exposure years. By LASSO regression, the important characteristic VOCs of the coal workers' pneumoconiosis group and the dust exposure group were n-hexane, methylcyclohexane and 4-methyl-2-pentanone, and the important characteristic VOCs of the coal workers' pneumoconiosis group and the healthy group were 2-methyl-pentane and 4-methyl-2-pentanone. The ROC analysis showed that the area under the curve (AUC) of n-hexane, methylcyclohexane, and 4-methyl-2-pentanone were 0.969, 0.909, and 0.956, respectively, and the AUC of combined diagnosis was 0.988 and its Youden index was 0.961, suggesting that these results can serve as a valuable reference for further research on early diagnosis. The Correlation analysis found that there was a positive correlation between n-hexane and lung function indicators in the important characteristic VOCs, indicating that it could indirectly reflect the obstruction of lung function ventilation, further proving that important characteristic VOCs have the potential to monitor lung function decline. Conclusion Three important characteristic VOCs selected in this study have the potential to be used as non-invasive biomarkers for early diagnosis and disease monitoring of coal workers' pneumoconiosis, and are worthy of further study and verification.

Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional’s skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.

Objective To identify risk factors associated with lymphatic leakage after laparoscopic radical prostatectomy(LRP)and to develop a machine learning-based nomogram for predicting such outcomes to support clinical prevention strategies.Methods We retrospectively analyzed perioperative data from 248 patients who underwent radical prostatectomy for prostate cancer between January 2020 and January 2024.Independent risk factors were identified through univariate and multivariate logistic regression analyses.A predictive model was developed,and its diagnostic performance was assessed by the area under the receiver operating characteristic curve(AUC).Five-fold cross-validation was performed to evaluate the model's generalizability.A nomogram was subsequently constructed to facilitate individualized risk quantification.Results Among the 248 patients,89(35.9%)developed lymphatic leakage,while 159(64.1%)did not.Independent risk factors for lymphatic leakage included intraopera-tive lymph node dissection(OR=5.415,95%CI:2.167～13.532,P<0.001),intraoperative plasma transfusion(OR=2.952,95%CI:1.524～5.718,P=0.001),and postoperative fasting duration of≥2 days(OR=1.412,95%CI:1.089～1.829,P=0.009).The predictive model showed good discrimination and calibration(AUC=0.711,95%CI:0.647～0.776,P<0.001;sensitivity:0.764;specificity:0.597).Model robustness was confirmed through five-fold cross-validation(training set AUC=0.822;test set AUC=0.829).The nomogram provided a clinically useful tool for quantifying individual risk of lymphatic leakage.Conclusions Intraoperative lymph node dissection,plasma transfusion,and postoperative fasting lasting≥2 days are independent risk factors for lymphatic leakage following radical prostatectomy.The validated predictive model demonstrates favorable clinical utility.

Objective To investigae microbial community structure of lower respiratory tract in severe hospital-acquired pneumonia(SHAP)patients in intensive care unit(ICU)using metagenomic next-generation sequencing(mNGS).Methods mNGS was performed on bronchoalveolar lavage fluid(BALF)of 84 patients with SHAP.Patients were grouped based on age,smoking status,underlying diseases and duration of artificial airway.The differences in α diversity,β diversity,microbial composition and community structure of airway microbiota were compared between different groups.The differential airway microbiota associated with artificial airway were screened,and microbial co-occurrence networks was constructed to observe the interaction in microorganisms.Results Results of α diversity analysis revealed that diversity and evenness of the microbial community were higher in young adults compared to those of middle-aged patients,while microbial diversity and evenness were significantly reduced in patients with comorbid stroke.In the group of artificial airway treatment,the diversity and uniformity of microorganisms decreased as the duration of artificial airway treatment increased.The diversity was the lowest when the artificial airway treatment lasted for more than 3 days.β diversity analysis confirmed that there were significant differences in the distinct microbial community structures between the>3 days support group and the non-intubated and≤3 days support cohorts.Acinetobacter baumannii was dominant in all groups.The bacterial diversity was significantly higher in the middle-aged group,the non-smoking group,the group without artificial airway therapy,the group without diabetes mellitus,the group with artificial airway therapy≥3 days and the group with chronic lung disease than those of other groups.In particular,pseudomonas aeruginosa,corynebacterium striatum and veillonella parvula were enriched in these groups.Difference analysis showed that there were significant differences in pseudomonas aeruginosa and corynebacterium striatum between the group with artificial airway treatment>3 days,the group without artificial airway therapy and the group with artificial airway treatment≤3 days.Network co-occurrence showed that there may be synergistic or antagonistic relationships between some microorganisms.Conclusion The microbial diversity of the lower respiratory tract in patients with SHAP significantly decreases in the elderly,those with concurrent stroke and those receiving artificial airway treatment.For these groups,rational use of antibiotics should be adopted to guide precise anti-infection treatment.

Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

Objective To investigate the expression level and clinical application value of circular RNA hsa_circ_0001766 in gastric cancer(GC)tissues and serum of patients with GC.Methods The PCR amplification products from GES-1 cells of normal gastric mucosa were analyzed for the cyclic sites of hsa_circ_0001766 by the Sanger sequencing technique.The expression levels of hsa_circ_0001766 in GES-1 cells treated or untreated with RNase R(RNase R)were detected by real-time fluorescence quantitative PCR(qRT-PCR).The expression levels of hsa_circ_0001766 in GC and adjacent tissues of 73 GC patients and serum samples of 34 GC patients were also detected by qRT-PCR.The receiver operating characteristics(ROC)curve was used to evaluate the clinical diag-nostic value of hsa_circ_0001766 in GC.The correlations between hsa_circ_0001766 and clinicopathological parameters in GC patients were also analyzed.Results There was cyclic sites in hsa_circ_0001766 and RNase R had no significant impact on the expression lev-el of hsa_circ_0001766 in GES-1 cells(t=1.678,P=0.169).Compared with adjacent tissues,the expression levels of hsa_circ_0001766 in GC tissues were significantly up-regulated(U=1 360,P<0.001).Compared with healthy controls,the expres-sion levels of hsa_circ_0001766 in serum of GC patients were significantly up-regulated(U=375,P<0.001).The area under the ROC curve(AUCROC),sensitivity,and specificity of hsa_circ_0001766 in GC tissues for diagnosing GC were 0.759(95％CI:0.682-0.837,P<0.000 1),79.45％,and 68.49％,respectively.The AUCROC,sensitivity,and specificity of serum hsa_circ_0001766 in diagnosing GC were 0.773(95％CI:0.662-0.884,P<0.000 1),73.53％,and 72.12％,respectively.The expression levels of hsa_circ_0001766 in GC tissues were correlated with lymph node metastasis(x2=5.509,P=0.019)and TNM staging(x2=5.161,P=0.023).The 3-year survival rate of GC patients with high expression of hsa_circ_0001766 in GC tissues was significantly lower than that with low ex-pression(x2=3.700,P=0.037).Conclusion The hsa_circ_0001766 in GC tissues and serum of GC patients is highly expressed,and its change in the expression level is of great significance for the diagnosis and prognostic evaluation of GC patients.

Objective:To investigate the diagnostic and differential diagnostic values of midbrain morphological measurements at the mammillary body level on axial cranial MRI in progressive supranuclear palsy (PSP).Methods:This cross-sectional study included 50 patients with clinically diagnosed, probable or possible PSP, admitted to Department of Neurology, Xuanwu Hospital, Capital Medical University from January 2023 to December 2024. Additionally, 44 patients with Parkinson's disease (PD), 30 patients with multiple system atrophy-cerebellar type (MSA-C), and 35 gender- and age-matched healthy controls recruited from the community were chosen. The following midbrain morphological parameters on axial cranial MRI were measured in all participants: distance from the interpeduncular fossa to the aqueduct (IF-AQ), distance from the lateral mesencephalic sulcus to the interpeduncular cistern (LS-IC), distance between the bilateral lateral mesencephalic sulci (D-BMS), cerebral peduncle angle (CPA), distance between the medial aspects of the cerebral peduncles (D-MP), and distance from the line connecting the highest points of the cerebral peduncle to the interpeduncular fossa (PP-IF). Differences in these measurements among the 4 groups were compared, and the diagnostic and differential diagnostic performances of each parameter in PSP was evaluated using receiver operating characteristic (ROC) curve.Results:The PSP group exhibited significantly shorter IF-AQ, LS-IC, and D-BMS distances compared with the other 3 groups ( P<0.05). (1) ROC curve analysis of PSP group versus non-PSP group (MSA-C patients, PD patients, and healthy controls) showed that IF-AQ had an area under the curve (AUC) of 0.977 (95% CI: 0.959-0.995, P<0.001), and at a cutoff of 10.895 mm, IF-AQ demonstrated a sensitivity of 96.0% and a specificity of 89.9% for diagnosing PSP; LS-IC had an AUC of 0.917 (95% CI: 0.868-0.966, P<0.001), and at a cutoff of 10.82 mm, LS-IC demonstrated a sensitivity of 82.0% and a specificity of 89.0% for diagnosing PSP; D-BMS had an AUC of 0.785 (95% CI: 0.704-0.866, P<0.001), and at a cutoff of 20.01 mm, D-BMS demonstrated a sensitivity of 66.0% and a specificity of 83.5% for diagnosing PSP. (2) In distinguishing PSP from MSA-C, IF-AQ achieved an AUC of 0.939 (95% CI: 0.889-0.988, P<0.001), with a sensitivity of 84.0% and a specificity of 90.0% at a cutoff of 10.385 mm; LS-IC achieved an AUC of 0.846 (95% CI: 0.756-0.936, P<0.001), with a sensitivity of 80.0% and a specificity of 76.7% at a cutoff of 10.710 mm; D-BMS achieved an AUC of 0.696 (95% CI: 0.578-0.813, P<0.001), with a sensitivity of 60.0% and a specificity of 80.0% at a cutoff of 19.810 mm. (3) In discriminating PSP from PD, IF-AQ yielded an AUC of 0.986 (95% CI: 0.970-1.000, P<0.001), with a sensitivity of 96.0% and a specificity of 89.2% at a cutoff of 10.955 mm; LS-IC achieved an AUC of 0.937 (95% CI: 0.885-0.988, P<0.001), with a sensitivity of 82.0% and a specificity of 95.5% at a cutoff of 10.820 mm; D-BMS had an AUC of 0.825 (95% CI: 0.740-0.909, P<0.001), with a sensitivity of 60.0% and a specificity of 95.5% at a cutoff of 19.820 mm. Conclusion:IF-AQ, LS-IC, and D-BMS distances on axial cranial MRI at the mamillary body level can diagnose and differentiate PSP to a certain extent, with IF-AQ enjoying the best efficacy.

Objective:To explore the genetic etiology of a child with Renpenning syndrome (RS), and review the literature on the clinical characteristics and gene mutations of RS.Methods:A child with RS (patient 1) who was diagnosed and treated in the Pediatric Intensive Care Unit of the Third Affiliated Hospital of Zhengzhou University in November 2023 was selected as the research object. The medical history, family history, physical examination, cerebrospinal fluid examination, echocardiography, brain magnetic resonance imaging (MRI), brain magnetic resonance angiography, cardiac coronary CT angiography and intelligence quotient (IQ) score of child 1 were retrospectively collected. Peripheral venous blood samples were collected from patient 1, his parents, sister and brother, respectively. Genomic DNA was extracted from the child and his family members, and three-whole exome sequencing (Trios-WES) was performed. Sanger sequencing was used to verify the pedigree. Bioinformatics softwares (Mutation Taster, REVEL, SIFT, PolyPhen-2, GERP+ +, SWISS-MODEL) were applied. The pathogenicity of the detected variants was rated according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the ACMG Guidelines). " PQBP1 gene" " Renpenning syndrome" " PQBP1 gene" " Renpenning syndrome" were used as keywords in Chinese and English, respectively. Case reports of patients with RS caused by PQBP1 gene variants were retrieved from Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed database. The clinical features and gene variants of RS caused by PQBP1 gene variants were summarized and analyzed. This study was reviewed by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Approval No. 2024-334-01). Results:The patient 1, a 12-year-old boy, was admitted to the hospital due to fever and disturbance of consciousness. Cerebrospinal fluid test showed viral encephalitis caused by human herpesvirus 7 infection. The main clinical manifestations were unusual facies (microcephaly, long narrow face, microphthalmos, superior oblique palpebral fissure, hypertelorism of inner canthus, bulbous nasal columella) and mental retardation. Auxiliary examination showed than patient 1 had atrial septal defect, nodular heterotopia in the posterior horn of the left ventricle, angiodysplasia, and low IQ. The disease began in infancy, and there was no family history of related diseases. A hemizygous deletion, c. 459_462del (p.Arg153SerfsTer41), was identified in exon 5 of the PQBP1 gene in patient 1, which was inherited from his mother by Sanger sequencing. The results of bioinformatics analysis showed that the mutation was harmful. This variant was rated as pathogenic (PVS1+ PS4+ PM2_Supporting+ PP3) according to ACMG Guidelines. According to the literature search strategy set in this study, a total of 13 cases of RS were retrieved, involving 16 cases of RS patient caused by PQBP1 gene mutation (patients 2-17), including patient 1, a total of 17 cases of RS. Among the 17 patients, 16 male patients had hemizygous mutations in the X chromosome PQBP1 gene, and 1 female patient had heterozygous mutations, including 12 deletion frameshift nonsense mutations, 3 point missense mutations, and 2 duplication mutations. Except for two fetuses, all patients had special facial features and low IQ to varying degrees. Ten patients had abnormal development of one or more organs such as eyes, heart, brain, etc. Conclusion:The main clinical manifestations of RS are developmental delay, long narrow face, bulbous nose, microcephaly, and may be accompanied by heterotopia of gray matter of ventricle and congenital heart disease. The c. 459_462del (p.Arg153SerfsTer41) variant of the PQBP1 gene is the genetic basis of patient 1 in this study.

Objectives:To investigate the incidence of tyrosine kinase inhibitor (TKI) withdrawal syndrome and psychological issues, and their associated factors, in patients with chronic-phase chronic myeloid leukemia (CML-CP) after TKI discontinuation.Methods:We retrospectively analyzed the clinical data of CML-CP patients who discontinued TKI therapy at Peking University People's Hospital after September 2012. Logistic regression models were used to identify independent factors associated with the occurrence of TKI withdrawal syndrome and psychological issues.Results:A total of 158 patients were included, of whom 92 (58%) were female. The median age at discontinuation was 50 ( IQR, 35-60) years. With a median follow-up of 25 ( IQR, 11-49) months, the 4-year rate of sustained major molecular response (MMR) was 60% (95% CI: 51%-70%) . Fifty-one (32%) patients experienced TKI withdrawal syndrome at a median of 1.3 ( IQR, 0.5-2.0) months after TKI discontinuation. Fifty-one (32%) patients reported psychological issues such as anxiety. These concerns stemmed from fears of fluctuating BCR::ABL1 levels or disease relapse, and, for those who discontinued TKI for pregnancy, worries about adverse fetal effects and/or the fetus inheriting CML. Multivariable analyses revealed that older age at discontinuation [ P=0.003 when adjusting for TKI therapy duration; P=0.002 when adjusting for deep molecular response (DMR) duration], longer TKI therapy duration ( P=0.010) , and longer DMR duration before discontinuation ( P=0.005) were significantly associated with a higher risk of TKI withdrawal syndrome; a university degree or higher ( P=0.010) and TKI discontinuation due to pregnancy or adverse events ( P=0.001) were significantly associated with psychological issues after discontinuation. The occurrence of TKI withdrawal syndrome or psychological issues had no impact on the probability of major molecular response loss after discontinuation. Conclusion:TKI withdrawal syndrome and psychological issues are common in CML patients who discontinue TKI therapy. Older age at discontinuation and longer TKI therapy duration or DMR duration are significantly associated with TKI withdrawal syndrome. Higher education level and TKI discontinuation due to pregnancy or adverse events are significantly associated with psychological issues.