ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T_1/2) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.
Humans ; Antiviral Agents/therapeutic use* ; Animals ; Male ; Adult ; Mice ; Female ; Endonucleases/antagonists & inhibitors* ; Influenza, Human/drug therapy* ; Young Adult ; Dibenzothiepins/pharmacology* ; Oseltamivir/pharmacology* ; Middle Aged ; Triazines/pharmacology* ; Thiepins/pharmacology* ; Influenza B virus/drug effects* ; Influenza A Virus, H1N1 Subtype/drug effects* ; Pyridines/pharmacology* ; Morpholines ; Pyridones

Objective:To construct a Harvard cancer index-based risk predictive model for perioperative venous thromboembolism (VTE) in elderly patients with femoral neck fracture and assess its predictive effectiveness.Methods:A retrospective cohort study was conducted to analyze the clinical data of 610 elderly patients with femoral neck fracture admitted to Peking Union Medical College Hospital between January 2013 and December 2022, including 193 males and 417 females, aged 60-99 years [(77.3±9.0)years]. The patients were divided into VTE group ( n=125) and non-VTE group ( n=485) according to occurrence of VTE during the perioperative period. The two groups were compared in terms of gender, age, body mass index, smoking status, alcohol consumption, time from fracture to admission, surgical waiting time, comorbidities, perioperative electrolyte disorders, past or present history of malignancy, past history of deep vein thrombosis (DVT) or pulmonary embolism (PE), and preoperative use of oral anticoagulants. Univariate analysis and multivariable stepwise Logistic regression analysis were conducted to evaluate and identify independent risk factors for perioperative VTE in elderly patients with femoral neck fracture. A perioperative VTE risk predictive model for elderly patients with femoral neck fracture was constructed using the Harvard cancer index: (1) assigning a risk score to each variable according to the corresponding conversion criteria of the Harvard cancer index and risk score, based on the magnitude of their ORs; (2) determining the exposure rate of each risk factor based on the population distribution observed in this study; (3) calculating the average population risk score; (4) computing the individual VTE risk score; (5) deriving the ratio (X) of each individual ′s VTE risk score to the population average. Based on the Harvard cancer index classification criteria for disease risk levels, individual VTE risk categories were determined. The predictive performance of the risk stratification was evaluated by comparing the incidence of VTE across different risk levels. The predictive performance of the model was evaluated based on sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC). The calibration of the model was assessed using the Hosmer-Lemeshow (H-L) test and internal validation was performed using the bootstrap resampling method with 1000 iterations. Results:Univariate analysis showed that gender, age, time from fracture to admission, surgical waiting time, previous cerebral infarction, stroke within the past month, Alzheimer′s disease, primary Parkinson′s syndrome, hysterectomy with bilateral adnexectomy, perioperative electrolyte disorders, history of DVT or PE, and preoperative use of oral anticoagulant drug were moderately associated with the occurrence of VTE in elderly patients with femoral neck fracture ( P<0.10). Multivariable stepwise logistic regression analysis demonstrated that female gender ( OR=2.26, 95% CI 1.34, 3.80, P<0.01), time from fracture to admission>1 day ( OR=3.70, 95% CI 2.24, 6.12, P<0.01), surgical waiting time>70 hours ( OR=2.06, 95% CI 1.29, 3.30, P<0.01), previous cerebral infarction ( OR=3.78, 95% CI 1.04, 13.76, P<0.05), stroke within the past month ( OR=11.57, 95% CI 1.21, 110.44, P<0.05), Alzheimer′s disease ( OR=3.26, 95% CI 1.12, 9.49, P<0.05), primary Parkinson ′s syndrome ( OR=3.47, 95% CI 1.22, 9.85, P<0.05), previous hysterectomy with bilateral adnexectomy ( OR=4.75, 95% CI 2.09, 10.80, P<0.01), perioperative electrolyte disorders ( OR=2.73, 95% CI 1.39, 5.35, P<0.01), and preoperative oral anticoagulant use ( OR=3.86, 95% CI 1.18, 12.67, P<0.05) were significantly associated with the occurrence of perioperative VTE in elderly patients with femoral neck fracture. Based on the above 10 risk factors, a perioperative VTE risk predictive model for elderly patients with femoral neck fracture was constructed with the Harvard cancer index. The formula was as follows: X=[10×(female gender)+25×(time from fracture to admission>1 day)+10×(surgical waiting time>70 hours)+25×(previous cerebral infarction)+50×(stroke within the past month)+25×(Alzheimer′s disease)+25×(primary Parkinson′s disease)+25×(previous hysterectomy with bilateral adnexectomy)+10×(perioperative electrolyte disorders)+25×(preoperative use of oral anticoagulant drug)]/33. Individualized VTE risk was classified into five levels: very low, low, moderate, high, and very high, with corresponding VTE rates of 4.8%, 11.8%, 14.9%, 32.3%, and 73.5%, respectively ( χ2=87.71, P<0.01). The VTE risk predictive model demonstrated an AUC of 0.74 (95% CI 0.69, 0.79, P<0.01), with a sensitivity of 63.2% and specificity of 74.8%. The H-L goodness-of-fit test indicated satisfactory model calibration ( P>0.05). The internal validation with the bootstrap method confirmed that the AUC remained 0.74. Conclusions:Female gender, time from fracture to admission>1 day, surgical waiting time>70 hours, previous cerebral infarction, stroke within the past month, Alzheimer′s disease, primary Parkinson′s syndrome, hysterectomy with bilateral adnexectomy, perioperative electrolyte disorders, and preoperative use of oral anticoagulant drug are independent risk factors for perioperative VTE in elderly patients with femoral neck fracture. Based on these factors, the perioperative VTE risk predictive model constructed using the Harvard cancer index demonstrates good clinical predictive value. Individualized VTE risk stratification can effectively identify high-, intermediate-, and low-risk populations, providing a valuable reference for tailoring anticoagulant prophylaxis strategies and enhancing postoperative surveillance.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To evaluate the efficacy and safety of telitacicept in the treatment of systemic lupus erythematosus (SLE) .Methods:The clinical data of 25 SLE patients who received standard therapy combined with telitacicept at the Department of Dermatology, Xiangya Second Hospital, Central South University, from 2021 to 2024 were retrospectively collected. Baseline demographic and clinical characteristics were analyzed. Changes in skin lesions, joint pain symptoms, complete blood count, and biochemical parameters at 4, 12, and 24 weeks of treatment were compared with baseline (week 0). The Wilcoxon signed-rank test was used to compare complement C3 and C4 levels before and after treatment, and univariate logistic regression analysis was performed to explore factors influencing the efficacy of telitacicept.Results:Among the 25 SLE patients, 3 were male (12.0%) and 22 were female (88.0%). Based on the SLE Disease Activity Index (SLEDAI) -2000 scores, 8 patients were mild, 13 were moderate, and 4 were severe. Of the 11 SLE patients with rashes before treatment, 6 achieved complete remission at 12 weeks. Among the 7 patients with joint pain before treatment, 4 experienced symptom resolution at 24 weeks. The proportion of patients with leukopenia at baseline and at 4, 12, and 24 weeks was 10/25 (40.0%), 0/24 (0), 1/22 (4.5%), and 2/19 (10.5%), respectively. The proportion of patients with thrombocytopenia was 6/25 (24.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively, and the proportion of patients with anemia was 7/25 (28.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively. At baseline, 11 out of 25 patients (44.0%) had proteinuria. At 12 weeks, the urinary protein quantification level (0.4 [0, 0.6] g/L) was significantly lower than at baseline (0.9 [0.8, 1.2] g/L). The SLE responder index-4 (SRI4) response rates at 4, 12, and 24 weeks were 14/18, 15/17, and 12/14, respectively. Complement C3 and C4 levels were significantly higher at 4, 12, and 24 weeks compared to baseline (all P < 0.001). Univariate logistic regression analysis showed that age, disease duration, glucocorticoid dosage, baseline complement C4 levels, antinuclear antibody titer, and SLEDAI-2K score did not significantly affect the efficacy of telitacicept (SRI4 response rate at 12 weeks) (all P > 0.05). No serious adverse reactions related to telitacicept were observed in patients. Conclusions:Telitacicept improved skin lesions, complement C3 and C4 levels, and anti-double-stranded DNA antibody levels in SLE patients. No association was found between the efficacy of telitacicept and baseline SLEDAI-2K scores, antinuclear antibody titers, or complement C4 levels, suggesting that telitacicept is an effective and safe treatment for SLE patients.

Objective:To investigate and explore the expressional condition and therapeutic role of PD-1 and CD161 in the peripheral blood of patients treated with PEG-IFN-α for chronic hepatitis B (CHB), and their correlation with the degree of decrease in hepatitis B surface antigen (HBsAg).Methods:A retrospective cohort study was conducted. CHB patients who visited the Second Affiliated Hospital of Xi'an Jiaotong University from July 2022 to December 2023 and healthy controls during the same period were included. Peripheral blood samples were collected from the IFN treatment group (31 cases), the non-IFN treatment group (30 cases), and the healthy control group (30 cases). Flow cytometry was used to detect the CD8, + PD-1, + CD161 + T lymphocytes and their subpopulations among the three groups. The proportions of cellular subpopulations were compared to analyze intergroup differences using Kruskal-Wallis and Mann-Whitney U tests. The patients in the IFN treatment group were divided into two subgroups, high-and low-level, according to the median levels of PD-1 + lymphocytes, CD8 +PD-1 +T cells, and CD161 + lymphocytes. The magnitude of HBsAg decline was compared between the two groups. Results:The proportions of PD-1 + lymphocytes and CD8 +PD-1 +T cells in the IFN treatment group were significantly higher than those in the healthy control group and the non-IFN treatment group ( P<0.001). Moreover, the proportions of PD-1 + lymphocytes [IFN treatment group 48 weeks: 24.3 (23.7, 28.0)%, non-IFN treatment group: 12.7 (10.0, 18.5)%, P<0.01] and CD8 +PD-1 +T cells [IFN treatment group 48 weeks: 29.29 (26.73, 32.98)%, non-IFN treatment group: 17.69 (9.62, 20.68)%, P<0.05] were higher in the IFN treatment group than those in the non-IFN treatment group at 48 weeks. The proportion of CD8 +CD161 +T cells was significantly lower in patients treated with IFN than in the non-IFN treatment group ( P<0.05) at 24 and 48 weeks, with no statistically significant difference with the healthy control group ( P>0.05). In the IFN treatment group, patients with high levels of PD-1 + and CD8 + PD1 lymphocytes had a significantly lower HBsAg decline compared to low-level patients, whereas no significant correlation was found between CD161 levels and HBsAg decline [PD-1 + lymphocytes: 0.15 (0.02, 0.18) log 10 IU/mL vs. 0.32 (0.13, 0.42) log 10 IU/mL, P<0.01; CD8 +PD-1 +T cells: 0.16 (0.03, 0.17) log 10 IU/mL vs. 0.34 (0.13, 0.44) log 10 IU/mL, P<0.05]. Conclusion:The proportions of CD8 +PD-1 +T cells and CD8 +CD161 +T cells were significantly regulated by PEG-IFN-α therapy in the peripheral blood of patients with CHB, revealing the important role of T cell immune activation status during antiviral treatment. The gradual decline of HBsAg is closely related to the high expression of PD-1, suggesting that PD-1 may be negatively regulated during the process of T cell exhaustion and immunological evasion.

Objective:To evaluate the efficacy and safety of telitacicept in the treatment of systemic lupus erythematosus (SLE) .Methods:The clinical data of 25 SLE patients who received standard therapy combined with telitacicept at the Department of Dermatology, Xiangya Second Hospital, Central South University, from 2021 to 2024 were retrospectively collected. Baseline demographic and clinical characteristics were analyzed. Changes in skin lesions, joint pain symptoms, complete blood count, and biochemical parameters at 4, 12, and 24 weeks of treatment were compared with baseline (week 0). The Wilcoxon signed-rank test was used to compare complement C3 and C4 levels before and after treatment, and univariate logistic regression analysis was performed to explore factors influencing the efficacy of telitacicept.Results:Among the 25 SLE patients, 3 were male (12.0%) and 22 were female (88.0%). Based on the SLE Disease Activity Index (SLEDAI) -2000 scores, 8 patients were mild, 13 were moderate, and 4 were severe. Of the 11 SLE patients with rashes before treatment, 6 achieved complete remission at 12 weeks. Among the 7 patients with joint pain before treatment, 4 experienced symptom resolution at 24 weeks. The proportion of patients with leukopenia at baseline and at 4, 12, and 24 weeks was 10/25 (40.0%), 0/24 (0), 1/22 (4.5%), and 2/19 (10.5%), respectively. The proportion of patients with thrombocytopenia was 6/25 (24.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively, and the proportion of patients with anemia was 7/25 (28.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively. At baseline, 11 out of 25 patients (44.0%) had proteinuria. At 12 weeks, the urinary protein quantification level (0.4 [0, 0.6] g/L) was significantly lower than at baseline (0.9 [0.8, 1.2] g/L). The SLE responder index-4 (SRI4) response rates at 4, 12, and 24 weeks were 14/18, 15/17, and 12/14, respectively. Complement C3 and C4 levels were significantly higher at 4, 12, and 24 weeks compared to baseline (all P < 0.001). Univariate logistic regression analysis showed that age, disease duration, glucocorticoid dosage, baseline complement C4 levels, antinuclear antibody titer, and SLEDAI-2K score did not significantly affect the efficacy of telitacicept (SRI4 response rate at 12 weeks) (all P > 0.05). No serious adverse reactions related to telitacicept were observed in patients. Conclusions:Telitacicept improved skin lesions, complement C3 and C4 levels, and anti-double-stranded DNA antibody levels in SLE patients. No association was found between the efficacy of telitacicept and baseline SLEDAI-2K scores, antinuclear antibody titers, or complement C4 levels, suggesting that telitacicept is an effective and safe treatment for SLE patients.

Objective:To construct a Harvard cancer index-based risk predictive model for perioperative venous thromboembolism (VTE) in elderly patients with femoral neck fracture and assess its predictive effectiveness.Methods:A retrospective cohort study was conducted to analyze the clinical data of 610 elderly patients with femoral neck fracture admitted to Peking Union Medical College Hospital between January 2013 and December 2022, including 193 males and 417 females, aged 60-99 years [(77.3±9.0)years]. The patients were divided into VTE group ( n=125) and non-VTE group ( n=485) according to occurrence of VTE during the perioperative period. The two groups were compared in terms of gender, age, body mass index, smoking status, alcohol consumption, time from fracture to admission, surgical waiting time, comorbidities, perioperative electrolyte disorders, past or present history of malignancy, past history of deep vein thrombosis (DVT) or pulmonary embolism (PE), and preoperative use of oral anticoagulants. Univariate analysis and multivariable stepwise Logistic regression analysis were conducted to evaluate and identify independent risk factors for perioperative VTE in elderly patients with femoral neck fracture. A perioperative VTE risk predictive model for elderly patients with femoral neck fracture was constructed using the Harvard cancer index: (1) assigning a risk score to each variable according to the corresponding conversion criteria of the Harvard cancer index and risk score, based on the magnitude of their ORs; (2) determining the exposure rate of each risk factor based on the population distribution observed in this study; (3) calculating the average population risk score; (4) computing the individual VTE risk score; (5) deriving the ratio (X) of each individual ′s VTE risk score to the population average. Based on the Harvard cancer index classification criteria for disease risk levels, individual VTE risk categories were determined. The predictive performance of the risk stratification was evaluated by comparing the incidence of VTE across different risk levels. The predictive performance of the model was evaluated based on sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC). The calibration of the model was assessed using the Hosmer-Lemeshow (H-L) test and internal validation was performed using the bootstrap resampling method with 1000 iterations. Results:Univariate analysis showed that gender, age, time from fracture to admission, surgical waiting time, previous cerebral infarction, stroke within the past month, Alzheimer′s disease, primary Parkinson′s syndrome, hysterectomy with bilateral adnexectomy, perioperative electrolyte disorders, history of DVT or PE, and preoperative use of oral anticoagulant drug were moderately associated with the occurrence of VTE in elderly patients with femoral neck fracture ( P<0.10). Multivariable stepwise logistic regression analysis demonstrated that female gender ( OR=2.26, 95% CI 1.34, 3.80, P<0.01), time from fracture to admission>1 day ( OR=3.70, 95% CI 2.24, 6.12, P<0.01), surgical waiting time>70 hours ( OR=2.06, 95% CI 1.29, 3.30, P<0.01), previous cerebral infarction ( OR=3.78, 95% CI 1.04, 13.76, P<0.05), stroke within the past month ( OR=11.57, 95% CI 1.21, 110.44, P<0.05), Alzheimer′s disease ( OR=3.26, 95% CI 1.12, 9.49, P<0.05), primary Parkinson ′s syndrome ( OR=3.47, 95% CI 1.22, 9.85, P<0.05), previous hysterectomy with bilateral adnexectomy ( OR=4.75, 95% CI 2.09, 10.80, P<0.01), perioperative electrolyte disorders ( OR=2.73, 95% CI 1.39, 5.35, P<0.01), and preoperative oral anticoagulant use ( OR=3.86, 95% CI 1.18, 12.67, P<0.05) were significantly associated with the occurrence of perioperative VTE in elderly patients with femoral neck fracture. Based on the above 10 risk factors, a perioperative VTE risk predictive model for elderly patients with femoral neck fracture was constructed with the Harvard cancer index. The formula was as follows: X=[10×(female gender)+25×(time from fracture to admission>1 day)+10×(surgical waiting time>70 hours)+25×(previous cerebral infarction)+50×(stroke within the past month)+25×(Alzheimer′s disease)+25×(primary Parkinson′s disease)+25×(previous hysterectomy with bilateral adnexectomy)+10×(perioperative electrolyte disorders)+25×(preoperative use of oral anticoagulant drug)]/33. Individualized VTE risk was classified into five levels: very low, low, moderate, high, and very high, with corresponding VTE rates of 4.8%, 11.8%, 14.9%, 32.3%, and 73.5%, respectively ( χ2=87.71, P<0.01). The VTE risk predictive model demonstrated an AUC of 0.74 (95% CI 0.69, 0.79, P<0.01), with a sensitivity of 63.2% and specificity of 74.8%. The H-L goodness-of-fit test indicated satisfactory model calibration ( P>0.05). The internal validation with the bootstrap method confirmed that the AUC remained 0.74. Conclusions:Female gender, time from fracture to admission>1 day, surgical waiting time>70 hours, previous cerebral infarction, stroke within the past month, Alzheimer′s disease, primary Parkinson′s syndrome, hysterectomy with bilateral adnexectomy, perioperative electrolyte disorders, and preoperative use of oral anticoagulant drug are independent risk factors for perioperative VTE in elderly patients with femoral neck fracture. Based on these factors, the perioperative VTE risk predictive model constructed using the Harvard cancer index demonstrates good clinical predictive value. Individualized VTE risk stratification can effectively identify high-, intermediate-, and low-risk populations, providing a valuable reference for tailoring anticoagulant prophylaxis strategies and enhancing postoperative surveillance.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To investigate and explore the expressional condition and therapeutic role of PD-1 and CD161 in the peripheral blood of patients treated with PEG-IFN-α for chronic hepatitis B (CHB), and their correlation with the degree of decrease in hepatitis B surface antigen (HBsAg).Methods:A retrospective cohort study was conducted. CHB patients who visited the Second Affiliated Hospital of Xi'an Jiaotong University from July 2022 to December 2023 and healthy controls during the same period were included. Peripheral blood samples were collected from the IFN treatment group (31 cases), the non-IFN treatment group (30 cases), and the healthy control group (30 cases). Flow cytometry was used to detect the CD8, + PD-1, + CD161 + T lymphocytes and their subpopulations among the three groups. The proportions of cellular subpopulations were compared to analyze intergroup differences using Kruskal-Wallis and Mann-Whitney U tests. The patients in the IFN treatment group were divided into two subgroups, high-and low-level, according to the median levels of PD-1 + lymphocytes, CD8 +PD-1 +T cells, and CD161 + lymphocytes. The magnitude of HBsAg decline was compared between the two groups. Results:The proportions of PD-1 + lymphocytes and CD8 +PD-1 +T cells in the IFN treatment group were significantly higher than those in the healthy control group and the non-IFN treatment group ( P<0.001). Moreover, the proportions of PD-1 + lymphocytes [IFN treatment group 48 weeks: 24.3 (23.7, 28.0)%, non-IFN treatment group: 12.7 (10.0, 18.5)%, P<0.01] and CD8 +PD-1 +T cells [IFN treatment group 48 weeks: 29.29 (26.73, 32.98)%, non-IFN treatment group: 17.69 (9.62, 20.68)%, P<0.05] were higher in the IFN treatment group than those in the non-IFN treatment group at 48 weeks. The proportion of CD8 +CD161 +T cells was significantly lower in patients treated with IFN than in the non-IFN treatment group ( P<0.05) at 24 and 48 weeks, with no statistically significant difference with the healthy control group ( P>0.05). In the IFN treatment group, patients with high levels of PD-1 + and CD8 + PD1 lymphocytes had a significantly lower HBsAg decline compared to low-level patients, whereas no significant correlation was found between CD161 levels and HBsAg decline [PD-1 + lymphocytes: 0.15 (0.02, 0.18) log 10 IU/mL vs. 0.32 (0.13, 0.42) log 10 IU/mL, P<0.01; CD8 +PD-1 +T cells: 0.16 (0.03, 0.17) log 10 IU/mL vs. 0.34 (0.13, 0.44) log 10 IU/mL, P<0.05]. Conclusion:The proportions of CD8 +PD-1 +T cells and CD8 +CD161 +T cells were significantly regulated by PEG-IFN-α therapy in the peripheral blood of patients with CHB, revealing the important role of T cell immune activation status during antiviral treatment. The gradual decline of HBsAg is closely related to the high expression of PD-1, suggesting that PD-1 may be negatively regulated during the process of T cell exhaustion and immunological evasion.

Objective:To explore the value of amide proton transfer-weighted (APTw) imaging and intravoxel incoherent motion (IVIM) imaging for diagnosing and evaluating the pathological differentiation of cervix squamous cell carcinoma (CSCC).Methods:This study was a diagnostic trial. Totally 56 patients pathologically diagnosed with CSCC at the First Hospital of Lanzhou University from October 2021 to October 2022 were retrospectively collected, as the CSCC group. And 36 female healthy volunteers who underwent physical examinations at the First Hospital of Lanzhou University from October 2021 to October 2023 were recruited as the control group. CSCC patients were divided into well-moderately differentiated ( n=34) and poorly differentiated groups ( n=22). The region of interest was placed in the lesions of CSCC group and normal cervical stroma of control group, and the quantitative parameters for asymmetric magnetization transfer ratio (MTR asym) of APTw imaging and pure diffusion coefficient (D), false diffusion coefficient (D *) and perfusion fraction (f) for IVIM were obtained. The independent sample t test was used to compare the differences in quantitative parameters between the two groups, the logistic regression model was used to establish combined parameters for the quantitative parameters with statistical significance between the two groups. The receiver operator characteristic curve was used to evaluate the diagnostic efficacy of single quantitative parameters and combined parameters to distinguish the CSCC group from the control group, and the well-moderately differentiated group from the poorly differentiated group in CSCC patients. The area under the curve (AUC) was compared using the DeLong test. Results:There were significant differences in MTR asym, D and f between CSCC group and control group ( t=-9.79, 10.09, 11.35, P<0.001). Also, significant differences were found for MTR asym and D between the well-moderately differentiated and poorly differentiated group ( t=4.11, -3.76, P<0.001). There was no significant difference in other quantitative parameters ( P>0.05). When comparing the CSCC group and control group, the AUC (95% CI) of MTR asym, D, f and combined parameter (MTR asym+D+f) were 0.887 (0.804-0.944), 0.940 (0.871-0.979), 0.968 (0.909-0.993), 0.995 (0.950-1.000). The AUC of the combined parameter was higher than those of MTR asym and D, with statistical significance ( Z=3.07, 2.06, P=0.002, 0.040). When comparing the well-moderately differentiated and poorly differentiated group, the AUC (95% CI) of MTR asym, D, and combined parameter (MTR asym+D) were 0.789 (0.660-0.887), 0.775 (0.644-0.876), 0.852 (0.731-0.932). There was no significant difference between each two AUCs ( P>0.05). Conclusion:The quantitative parameters of APTw and IVIM imaging can be used to diagnose and preliminarily evaluate the pathological differentiation of CSCC. Joint parameters can improve the diagnostic efficiency of CSCC.