1.Study on the stability of PBMCs recovered from leukocyte-depleted filter residues
Ju LIN ; Zhiqiang XIANG ; Dongfen DU ; Fang YUAN ; Miaoyu WANG ; Yue WU ; Kaiyu HUANG ; Lieyong SANG
Chinese Journal of Blood Transfusion 2025;38(5):723-733
Objective: To identify an optimal back-flush solution for leukocyte-depleted filters that maximizes peripheral blood mononuclear cell (PBMC) recovery with high viability, long-term storage stability, and sterility of the harvested residues, thereby providing a clinically translatable strategy. Methods: Three sterile bag-packaged solutions—Saline, Solvent, and Hanks' balanced salt solution (HBSS)—were used to back-flush randomly assigned leukocyte-depleted filters. Nucleated cell recovery rate and viability of the harvested residues were compared. The optimal solution identified was applied to an expanded sample set. PBMC viability and yield were evaluated after 1h vs 48h storage of the residues. PBMCs isolated from the residues were cryopreserved in liquid nitrogen for 1 month, followed by post-thaw comparisons of viability and T-cell expansion capacity. Results: The Solvent group achieved the highest and most consistent nucleated cell recovery rate. Post-flush recovery rate from filters after 400 mL whole blood processing was (21.3±1.6)% for the Solvent group, significantly higher than Saline group (19.2±6.3)% and HBSS group (11.2±5.0)%, with residues from all groups maintaining viability >90%. No biologically significant difference in residue viability was observed between 48h vs 1h storage groups (93.3±2.3)% vs (95.7±1.8)%). PBMC recovery rates from residues showed no statistical difference between 48h vs 1h storage groups [(48.2%±9.5%)vs (40.41%±8.35%), P>0.05], with (17.7±2.6)×10
cells. After 1-month cryopreservation and 10-day expansion, PBMCs isolated from 48-hour-stored residues retained (91.2±3.2)% viability and achieved a (61.9±15.9)-fold expansion. Conclusion: The bag-packaged Solvent, as a back-flush solution, enables sterile acquisition of leukocyte-depleted filter residues through closed-system tubing connections. These residues maintained PBMC viability and recovery rates after 48h storage at 2℃-8℃, with post-cryopreservation (1-month liquid nitrogen) viability and expansion capacity remaining stable. This protocol complies with blood bank regulatory criteria, addresses the concerns about the infectious window period in cell therapy raw materials, and provides a clinically translatable strategy for PBMC-based applications.
2.Study on relationships of MS4A1 gene polymorphism with blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma
Feng SHI ; Tao LIU ; He HUANG ; Caifu FANG ; Shaoxing GUAN ; Zhang ZHANG ; Zhao WANG ; Xiaojie FANG ; Zhuojia CHEN ; Shu LIU
China Pharmacy 2025;36(13):1641-1647
OBJECTIVE To explore the effects of CD20 coding gene (MS4A1) polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020, with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software, including rs1051461, rs17155034, rs4939364, and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors(demographic, clinical, and genotypic variables) in patients and the steady-state trough concentration of rituximab during the first course of treatment, followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival (PFS) and overall survival (OS). Using MS4A1 genotype and tumor stage as independent variables, Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL,which was significantly lower than 21.95 μg/mL in AA+AC carriers (P<0.05). The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers, CT+TT carriers had significantly prolonged PFS and OS (P<0.05). The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype (HR=4.406, 95%CI:1.743-11.137, P<0.05) and tumor Ⅲ&Ⅳ (HR=3.233, 95%CI: 1.413-7.399, P<0.05) were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab, and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.
3.Correlation of physical activity and screen time with anxiety and depressive symptoms among college students
Chinese Journal of School Health 2025;46(9):1303-1306
Objective:
To analyze the correlation of physical activity and screen time with anxiety and depressive symptoms among college students, so as to provide a reference for formulating intervention measures for anxiety and depressive symptoms among college students.
Methods:
In May 2024, the method of combining convenient sampling with stratified sampling was adopted to select 3 076 college students from 5 colleges in Shaoxing of Zhejiang Province. Self compiled general situation questionnaires, Screen Time Questionnaire, Selfrating Anxiety Scale and Self rating Depression Scale were used to investigate the current status of college students physical activities, screen time, anxiety and depressive symptoms, etc. Inter group comparisons were conducted by using the χ 2 test, Fisher s exact probability test, t-test or analysis of variance. A multivariate Logistic regression model was established to explore the correlations between physical activity, screen time with anxiety and depressive symptoms among college students.
Results:
The constituent ratios of mild, moderate and severe anxiety symptoms were 59.97%, 28.99% and 11.04%, respectively. The constituent ratios of mild, moderate and severe depressive symptoms were 64.96%, 29.92% and 5.12%, respectively. There were statistically significant differences in the detection rates of anxiety symptom ( χ 2=15.99) and depressive symptom ( χ 2=16.54) among college students of different grades and screen time daily (both P <0.05). There were statistically significant differences in physical activity among college students of different genders and subject types ( t/F =11.67, 11.90, both P <0.01). Multivariate Logistic regression analysis showed that when physical activity was at least 1 hour per week <3 d, a screen time <2 h/d could reduce the risk of anxiety symptoms among college students ( OR =0.57), and screen time <2, 2-<3, 3-<4 h/d could reduce the risk of depressive symptoms among college students ( OR =0.65, 0.56, 0.64); when the number of days of physical activity exercise was at least 1 h per week ≥3 d, the occurrence risks of anxiety symptom( OR =0.49, 0.58) and depressive symptom ( OR =0.36, 0.43) were reduced for students with screen time <2 and 2-<3 h/d (all P <0.05).
Conclusions
There are correlations of physical activity and screen time with anxiety and depressive symptoms among college students. Low physical activity and longer screen time are more likely to increase the risk of anxiety and depressive symptom among college students.
4.Hearing loss prevalence and burden of disease in China: Findings from provincial-level analysis.
Yu WANG ; Yang XIE ; Minghao WANG ; Mengdan ZHAO ; Rui GONG ; Ying XIN ; Jia KE ; Ke ZHANG ; Shaoxing ZHANG ; Chen DU ; Qingchuan DUAN ; Fang WANG ; Tao PAN ; Furong MA ; Xiangyang HU
Chinese Medical Journal 2025;138(1):41-48
BACKGROUND:
Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society.
METHODS:
We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China.
RESULTS:
An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015.
CONCLUSIONS
The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans
;
China/epidemiology*
;
Hearing Loss/epidemiology*
;
Prevalence
;
Middle Aged
;
Male
;
Female
;
Adult
;
Aged
;
Adolescent
;
Young Adult
;
Child
;
Child, Preschool
;
Infant
;
Aged, 80 and over
;
Cost of Illness
5.Long-term safety and effectiveness of roxadustat in Chinese patients with chronic kidney disease-associated anemia: The ROXSTAR registry.
Xiaoying DU ; Yaomin WANG ; Haifeng YU ; Jurong YANG ; Weiming HE ; Zunsong WANG ; Dongwen ZHENG ; Xiaowei LI ; Shuijuan SHEN ; Dong SUN ; Weimin YU ; Detian LI ; Changyun QIAN ; Yiqing WU ; Shuting PAN ; Jianghua CHEN
Chinese Medical Journal 2025;138(12):1465-1476
BACKGROUND:
Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China.
METHODS:
This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion.
RESULTS:
The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon.
CONCLUSIONS:
Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings.
REGISTRATION
Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans
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Male
;
Female
;
Anemia/etiology*
;
Middle Aged
;
Renal Insufficiency, Chronic/complications*
;
Glycine/adverse effects*
;
Isoquinolines/adverse effects*
;
Aged
;
Prospective Studies
;
Adult
;
Hemoglobins/metabolism*
;
Treatment Outcome
;
China
;
Registries
;
East Asian People
6.Impact and action mechanisms of obesity on male reproductive function: An update.
Ran WEI ; Zhe-Tao LANG ; Er-Hui WANG
National Journal of Andrology 2025;31(4):357-362
The adverse effects of obesity on male reproductive function are mainly manifested as the abnormal development of the reproductive system, decrease of testosterone level, decline of sperm quality, and impact on the health of offspring, while its regulatory mechanism is far from being clarified. This paper expounds the influence of obesity on the male reproductive system in the aspects of population epidemiology and animal experiments, presents an overview on the action mechanisms of obesity from the perspectives of the hypothalamus-pituitary-testis axis, blood-testis barrier, inflammatory reaction, oxidative stress, testicular germ cell apoptosis, and impact of paternal obesity on the health of offspring, aiming to shed some light on the clinical treatment and prevention of obesity-related male reproductive dysfunction.
Male
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Obesity/physiopathology*
;
Humans
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Animals
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Hypothalamo-Hypophyseal System
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Testis/physiopathology*
;
Oxidative Stress
;
Infertility, Male/etiology*
;
Reproduction
;
Blood-Testis Barrier
7.Nomogram prediction model for factors associated with vascular plaques in a physical examination population.
Xiaoling ZHU ; Lei YAN ; Li TANG ; Jiangang WANG ; Yazhang GUO ; Pingting YANG
Journal of Central South University(Medical Sciences) 2025;50(7):1167-1178
OBJECTIVES:
Cardiovascular disease (CVD) poses a major threat to global health. Evaluating atherosclerosis in asymptomatic individuals can help identify those at high risk of CVD. This study aims to establish an individualized nomogram prediction model to estimate the risk of vascular plaque formation in asymptomatic individuals.
METHODS:
A total of 5 655 participants who underwent CVD screening at the Health Management Center of The Third Xiangya Hospital, Central South University, between January 2022 and June 2024 we retrospectively enrolled. Using simple random sampling, participants were divided into a training set (n=4 524) and a validation set (n=1 131) in an 8꞉2 ratio. Demographic and clinical data were collected and compared between groups. Multivariate logistic regression analysis was used to identify independent factors associated with vascular plaques and to construct a nomogram prediction model. The predictive performance and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves, the Hosmer-Lemeshow goodness-of-fit test, calibration plots, and decision curve analysis (DCA).
RESULTS:
The mean age of participants was 52 years old. There were 3 400 males (60.12%). The overall detection rate of vascular plaque in the screening population was 49.87% (2 820/5 655). No statistically significant differences were observed in clinical indicators between the training and validation sets (all P>0.05). Multivariate Logistic regression analysis identified age, systolic blood pressure, high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipoprotein(a), male sex, smoking history, hypertension history, and diabetes history as independent risk factors for vascular plaque in asymptomatic individuals (all P<0.05). The area under the curve (AUC) of the nomogram model for predicting vascular plaque risk were 0.778 (95% CI 0.765 to 0.791, P<0.001) in the training set and 0.760 (95% CI 0.732 to 0.787, P<0.001) in the validation set. The Hosmer-Lemeshow goodness-of-fit test indicated good model calibration (training set: P=0.628; validation set: P=0.561). The calibration curve plotted using the Bootstrap method demonstrated good agreement between predicted probabilities and actual probabilities. DCA showed that the nomogram provided a clinical net benefit for predicting vascular plaque risk when the threshold probability ranged from 0.02 to 0.99.
CONCLUSIONS
The nomogram prediction model for vascular plaque risk, constructed using readily available and cost-effective physical examination indicators, exhibited good predictive performance. This model can assist in the early identification and intervention of asymptomatic individuals at high risk for cardiovascular disease.
Humans
;
Male
;
Middle Aged
;
Female
;
Nomograms
;
Retrospective Studies
;
Risk Factors
;
Plaque, Atherosclerotic/diagnosis*
;
Aged
;
Adult
;
Physical Examination
;
Logistic Models
;
Cardiovascular Diseases/epidemiology*
;
ROC Curve
8.Mechanism of human embryonic stem cell-derived mesenchymal stem cells on alleviating brain injury after cardiopulmonary resuscitation in swine with cardiac arrest.
Feng GE ; Jiefeng XU ; Jinjiang ZHU ; Guangli CAO ; Xuguang WANG ; Meiya ZHOU ; Tiejiang CHEN ; Mao ZHANG
Chinese Critical Care Medicine 2025;37(2):133-139
OBJECTIVE:
To investigate the mechanism of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC) in alleviating brain injury after resuscitation in swine with cardiac arrest (CA).
METHODS:
Twenty-nine healthy male large white swine were randomly divided into Sham group (n = 9), cardiopulmonary resuscitation (CPR) group (n = 10) and hESC-MSC group (n = 10). The Sham group only completed animal preparation. In CPR group and hESC-MSC group, the swine model of CA-CPR was established by inducing ventricular fibrillation for 10 minutes with electrical stimulation and CPR for 6 minutes. At 5 minutes after successful resuscitation, hESC-MSC 2.5×106/kg was injected via intravenous micropump within 1 hour in hESC-MSC group. Venous blood samples were collected before resuscitation and at 4, 8, 24, 48 and 72 hours of resuscitation. The levels of neuron specific enolase (NSE) and S100B protein (S100B) were detected by enzyme linked immunosorbent assay (ELISA). At 24, 48 and 72 hours of resuscitation, neurological deficit score (NDS) and cerebral performance category (CPC) were used to evaluate the neurological function of the animals. Three animals from each group were randomly selected and euthanized at 24, 48, and 72 hours of resuscitation, and the hippocampus tissues were quickly obtained. Immunofluorescence staining was used to detect the distribution of hESC-MSC in hippocampus. Immunohistochemical staining was used to detect the activation of astrocytes and microglia and the survival of neurons in the hippocampus. The degree of apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL).
RESULTS:
The serum NSE and S100B levels of brain injury markers in CPR group and hESC-MSC group were significantly higher than those in Sham group at 24 hours of resuscitation, and then gradually increased. The levels of NSE and S100B in serum at each time of resuscitation in hESC-MSC group were significantly lower than those in CPR group [NSE (μg/L): 20.69±3.62 vs. 28.95±3.48 at 4 hours, 27.04±5.56 vs. 48.59±9.22 at 72 hours; S100B (μg/L): 2.29±0.39 vs. 3.60±0.73 at 4 hours, 2.38±0.15 vs. 3.92±0.50 at 72 hours, all P < 0.05]. In terms of neurological function, compared with the Sham group, the NDS score and CPC score in the CPR group and hESC-MSC group increased significantly at 24 hours of resuscitation, and then gradually decreased. The NDS and CPC scores of hESC-MSC group were significantly lower than those of CPR group at 24 hours of resuscitation (NDS: 111.67±20.21 vs. 170.00±21.79, CPC: 2.33±0.29 vs. 3.00±0.00, both P < 0.05). The expression of hESC-MSC positive markers CD73, CD90 and CD105 in the hippocampus of hESC-MSC group at 24, 48 and 72 hours of resuscitation was observed under fluorescence microscope, indicating that hESC-MSC could homing to the damaged hippocampus. In addition, compared with Sham group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of CPR group were significantly increased, and the proportion of neurons was significantly decreased at 24, 48 and 72 hours of resuscitation. Compared with CPR group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of hESC-MSC group decreased and the proportion of neurons increased significantly at 24 hours of resuscitation [proportion of astrocytes: (14.33±1.00)% vs. (30.78±2.69)%, proportion of microglia: (12.00±0.88)% vs. (27.89±5.68)%, apoptotic index: (12.89±3.86)% vs. (52.33±7.77)%, proportion of neurons: (39.44±3.72)% vs. (28.33±1.53)%, all P < 0.05].
CONCLUSIONS
Application of hESC-MSC at the early stage of resuscitation can reduce the brain injury and neurological dysfunction after resuscitation in swine with CA. The mechanism may be related to the inhibition of immune cell activation, reduction of cell apoptosis and promotion of neuronal survival.
Animals
;
Heart Arrest/therapy*
;
Cardiopulmonary Resuscitation
;
Swine
;
Humans
;
Male
;
Human Embryonic Stem Cells/cytology*
;
Mesenchymal Stem Cell Transplantation
;
Mesenchymal Stem Cells/cytology*
;
Phosphopyruvate Hydratase/blood*
;
Brain Injuries/therapy*
;
S100 Calcium Binding Protein beta Subunit
;
Apoptosis
;
Disease Models, Animal
9.Metagenomic Next-Generation Sequencing-Assisted Diagnosis of Japanese Spotted Fever: Report of One Case.
Yong-Chun RUAN ; Yi-Qing ZHOU ; Hai-Wang ZHANG ; Jie ZHOU ; Jin-Nan DUAN ; Xiao-Jing ZHANG ; L I MING-HUI
Acta Academiae Medicinae Sinicae 2025;47(1):146-149
Japanese spotted fever(JSF)is an infectious disease caused by Rickettsia japonica,with nonspecific clinical symptoms and a high risk of misdiagnosis.We reported a case of JSF,in which Rickettsia japonica was detected in blood cells by metagenomic next-generation sequencing.The patient recovered after treatment with doxycycline.This report provides a reference for the clinical diagnosis and treatment of JSF.
Humans
;
High-Throughput Nucleotide Sequencing
;
Metagenomics
;
Rickettsia/isolation & purification*
;
Spotted Fever Group Rickettsiosis/microbiology*
10.Association between the non-treatment threshold or upper limit of normal of alanine aminotransferase and liver pathological injury in patients with chronic hepatitis B virus infection and a persistently low level of alanine aminotransferase
Ming SHU ; Suwen JIANG ; Airong HU ; Qin CHEN ; Jialan WANG ; Menghan JIN ; Haojin ZHANG ; Shiqi YANG ; Shiyang FAN
Journal of Clinical Hepatology 2025;41(10):2044-2053
ObjectiveTo investigate the significance of different non-treatment thresholds or upper limits of normal (ULN) of alanine aminotransferase (ALT) in evaluating significant liver pathological injury in patients with chronic hepatitis B virus (HBV) infection, and to provide guidance for clinical diagnosis and treatment. MethodsThis study was conducted among 733 patients with chronic HBV infection who were hospitalized in Ningbo No. 2 Hospital from January 2015 to December 2023 and underwent liver biopsy and histopathological examination, and all patients had a persistent ALT level of ≤40 U/L and positive HBV DNA (>30 IU/mL). According to the treatment threshold or ULN of ALT, the patients were divided into group 1 with 575 patients (≤35 U/L for male patients, ≤25 U/L for female patients), group 2 with 430 patients (≤30 U/L for male patients, ≤19 U/L for female patients), group 3 with 443 patients (≤27 U/L for male patients, ≤24 U/L for female patients), group 4 with 446 patients (≤25 U/L), group 5 with 158 patients (>35 U/L for male patients, >25 U/L for female patients), and group 6 with 145 patients (>30 — ≤35 U/L for male patients, >19 — ≤25 U/L for female patients). Groups 2, 5, and 6 were compared to analyze the severity of liver pathological injury in patients with different ALT levels and the constituent ratio of patients with significant liver pathological injury, and groups 1, 2, 3, and 4 were compared to investigate the value of different ULN or non-treatment thresholds of ALT in determining liver inflammation grade (G), liver fibrosis stage (S), and the treatment indication based on liver pathology. The independent-samples t test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test or the Tambane’s test was used for further comparison between two groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups; a Ridit analysis was used for comparison of ranked data. A multivariate Logistic regression analysis (forward stepwise) was performed with whether liver pathology met the treatment indication (≥G2 and/or ≥S2) as the dependent variable and related factors with a significant impact on the dependent variable (P <0.05) as the independent variable. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC), as well as sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio, was used to assess the diagnostic value of different non-treatment thresholds of ALT. ResultsAmong the 733 patients, 259 (35.33%) had ≥G2 liver inflammation, 211 (28.79%) had ≥S2 liver fibrosis, and 306 (41.75%) had treatment indication (≥G2 and/or ≥S2). There was a significant difference in liver inflammation grade (G0 — G4) between groups 2, 5, and 6 (χ2=22.869, P <0.001), and there were also significant differences in the constituent ratios of patients with ≥G2 or ≥G3 liver inflammation between the three groups (χ2=21.742 and 14.921, P<0.001 and P=0.001). There was a significant difference in liver fibrosis stage (S0 — S4) between groups 2, 5, and 6 (χ2=16.565, P<0.001), and there were also significant differences in the constituent ratios of patients with ≥S2, ≥S3 or S4 liver fibrosis between the three groups (χ2=13.264, 13.050, and 6.260, P=0.001, 0.001, and 0.044). There were significant differences between groups 2, 5, and 6 in the constituent ratios of patients with or without treatment indication based on liver pathology (χ2=20.728, P<0.001). There were significant differences between groups 2, 5, and 6 in the constituent ratio of male patients (χ2=24.836, P<0.05), age (F=5.710, P<0.05), ALT (F=473.193, P<0.05), aspartate aminotransferase (AST) (F=107.774, P<0.05), ALT/AST ratio (F=40.167, P<0.05), γ-glutamyl transpeptidase (GGT) (H=15.463, P<0.05), aspartate aminotransferase-to-platelet ratio index (APRI) (H=63.024, P<0.05), and LIF-5 (5 indicators for liver inflammation and fibrosis) (H=46.397, P<0.05). In groups 1 — 4, compared with the patients without treatment indication, the patients with treatment indication had a significantly lower constituent ratio of patients with positive HBeAg, significantly lower levels of platelet count (PLT) and HBV DNA, and significantly higher age, ALT, AST, GGT, APRI, FIB-4, and LIF-5 (all P<0.05). The Logistic regression analysis showed that age (odds ratio [OR]=1.044, 95% confidence interval [CI]: 1.025 — 1.063, P<0.001), GGT (OR=1.022, 95%CI: 1.007 — 1.038, P=0.003), and HBV DNA (OR=0.839, 95%CI: 0.765 — 0.919, P<0.001) were influencing factors for treatment indication based on liver pathology in group 1; HBeAg (OR=1.978, 95%CI: 1.269 — 3.082, P=0.003), age (OR=1.048, 95%CI: 1.025 — 1.071, P<0.001), GGT (OR=1.016, 95%CI: 1.001 — 1.031, P=0.041), and PLT (OR=0.995, 95%CI: 0.991 — 1.000, P=0.049) were influencing factors in group 2; age (OR=1.040, 95%CI: 1.014 — 1.066, P=0.002), ALT (OR=1.047, 95%CI: 1.005 — 1.092, P=0.029), HBV DNA (OR=0.817, 95%CI: 0.736 — 0.907, P<0.001), and LIF-5 (OR=7.382, 95%CI: 1.151 — 47.330, P=0.035) were influencing factors in group 3; age (OR=1.054, 95%CI: 1.031 — 1.077, P<0.001), ALT (OR=1.061, 95%CI: 1.016 — 1.107, P=0.008), and HBV DNA (OR=0.825, 95%CI: 0.743 — 0.917, P<0.001) were influencing factors in group 4. The diagnostic performance for identifying ≥G2 liver inflammation, ≥S2 liver fibrosis, and treatment indication in groups 1 — 4 had an AUC of >0.7; group 1 showed the lowest sensitivity (28.76%) and the highest specificity, positive predictive value, positive likelihood ratio, and negative likelihood ratio in judging treatment indication; group 2 had the highest sensitivity and negative predictive value and the lowest negative likelihood ratio; groups 3 and 4 had similar diagnostic indicators. ConclusionIn patients with chronic HBV infection and a persistently low ALT level, the severity of liver histopathological injury and the constituent ratio of significant liver histopathological injury decrease with the reduction in ALT level. A higher non-treatment threshold or ULN of ALT can help to identify the patients requiring treatment (with a higher specificity), while a lower non-treatment threshold or ULN of ALT can help to identify the patients who do not require treatment (with a higher sensitivity).


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