Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Emergence agitation(EA)is a common complication after general anesthesia,especially in children and adolescents.Remifentanil,as a short-acting μ-receptor agonist,has become an important drug for the prevention and treatment of EA due to its rapid recovery and low risk of respiratory depression.This article reviews the mechanism of action and clinical research progress of remifentanil in the prevention and treatment of EA.Its mechanism of action involves the inhibition of pain signals mediated by traditional μ-receptor activation and potential new mechanism based on neural-endocrine-immune network,including regulation of microglial inflammatory pathways,and the modulation of cytokines and chemokines,etc.Clinical studies have shown that remifentanil can significantly shorten the recovery time,reduce the incidence of EA,and further optimize the analgesic effect and recovery quality by combining with other drugs(such as local anesthetics,sedatives,and opioid drugs).Future research should further explore the mechanism of action of remifentanil,optimize clinical treatment strategies,and conduct large-scale clinical trials to standardize the drug use plan,while paying attention to its long-term effects and the development of multimodal treatment plans to promote the further development of EA prevention and treatment plans.

Objective:To evaluate the effect of disulfiram on sepsis-associated encephalopathy (SAE) and the relationship with NOD-like receptor family pyrin domain-containing 3 (NLRP3)/caspase-1 signaling pathway in rats.Methods:Forty-five SPF healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-220 g, were divided into 3 groups ( n=15 each) using a random number table method: sham operation group, SAE group, and SAE+ disulfiram group (SAE+ DSF group). The SAE model was established by by using cecal ligation and puncture in anesthetized rats. SAE+ DSF group received an intraperitoneal injection of 50 mg/kg disulfiram 4 h before the cecal ligation and puncture. The survival status of rats was recorded within 72 h after surgery. Their neurobehavioral scores were assessed and recorded on days 1-3 after surgery. On the 3rd day after surgery, novel object recognition test (cognitive index) and open field test (activity distance and time in the central area) were conducted sequentially. Following the behavioral testing, the rats were anesthetized, and their hippocampi were dissected and isolated to observe the pathological changes in the hippocampal region (using HE staining) and to determine the expression of NLRP3 and caspase-1 (by Western blot) and the expression of interleukin-1beta (IL-1β), IL-18 and tumor necrosis factor-alpha (TNF-α) mRNA (by fluorescent quantitative polymerase chain reaction). Results:Compared with Sham group, the 72-h survival rate and postoperative neurobehavioral scores were significantly decreased, the activity distance and time in the central area of the open field were shortened, and the cognitive index was decreased, the expression of NLRP3, caspase-1 and IL-1β, IL-18 and TNF-α mRNA was up-regulated ( P<0.05), and the pathological damage was marked in the hippocampus in SAE group ( P<0.05). Compared with SAE group, postoperative neurobehavioral scores were significantly increased, the activity distance and time in the central area of the open field were prolonged, the cognitive index was increased, and the expression of NLRP3 and caspase-1 and IL-1β, IL-18 and TNF-α mRNA was down-regulated ( P<0.05), no significant change was found in the 72-h survival rate ( P>0.05), and the pathological damage to the hippocampus was significantly alleviated in SAE+ DSF group. Conclusions:Disulfiram can alleviate SAE in rats, and the mechanism may be related to the inhibition of the NLRP3/caspase-1 signaling pathway.

Objective To investigate the predictive value of pan-immune-inflammation value(PIV),blood urea nitrogen to albumin ratio(BAR),collateral circulation and National Institutes of Health stroke scale(NIHSS)score for disease progression and short-term prognosis in patients with acute perforating artery cerebral infarction(APACI).Methods Patients with APACI admitted to the Neurology Department of Anhui NO.2 Provincial People's Hospital from January 2019 to October 2024 were retrospectively enrolled in this study.General and clinical data,including age,gender,previous history(hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,drinking history,NIHSS scores at admission were collected.Fasting venous blood samples were collected from the patients within 24 h after admission to detect levels of neutrophils,lymphocytes,monocytes,platelets,blood urea nitrogen,and serum albumin.PIV(PIV=neutrophils × platelets × monocytes/lymphocytes)and BAR were calculated.The location of lesions and Fazekas classification of white matter lesions were evaluated using head MRI and MR angiography at admission.Collateral circulation status was assessed based on CT angiography upon admission.Disease progression was defined through comparing the NIHSS score at 72-hour after admission to the score at admission(an increase of 2 or more points in NIHSS score indicating disease progression).The patients were divided into a progression group and a non-progression group based on the increase in NIHSS score,as aforementioned.Patients follow-up was conducted through phone call or outpatient visits at 90 d after discharge.The modified Rankin scale(mRS)was used to evaluate the prognosis,with a mRS score of 0-2 indicates good prognosis,and a 3-6 indicates poor prognosis.Factors with statistically significant differences in univariate analysis were included in a multivariate Logistic regression analysis to explore the influencing factors of disease progression and poor prognosis in patients with APACI.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each indicator for disease progression and poor prognosis in patients with APACI.Results A total of 165 patients with APACI were enrolled in this study,including 121 males and 44 females,aged 27-86 years,with an average of(61±11)years.Among all patients enrolled,56 patients were included in the progression group and 109 patients in the non-progression group,124 patients showed good prognosis and 41 patients had poor prognosis.No statistically significant differences were found in age,gender,smoking history,drinking history,hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and Fazekas classification of white matter lesions between the progression group and the non-progression group(all P＞0.05).While the NIHSS score at admission,proportion of poor collateral circulation,PIV and BAR in the progression group were significantly higher than those in the non-progression group(all P＜0.05).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.177,95％CI 1.001-1.384,P=0.049),poor collateral circulation(OR,3.107,95％CI 1.216-7.939,P=0.018),high PIV(OR,1.006,95％CI 1.003-1.009,P=0.001),and high BAR(OR,1.610 × 109,95％CI 5.769 × 104-4.494 × 1013,P＜0.01)were independent risk factors of disease progression in patients with APACI.ROC curve analysis results showed that the area under the curve(AUC)of combination of PIV,BAR,collateral circulation and NIHSS score at admission for predicting disease progression in patients with APACI was 0.914(95％ CI0.861-0.952,P＜0.01),which was greater than that of each indicator(all P＜0.05).No statistically significant differences were found in smoking,drinking,hypertension,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and BAR between the poor prognosis and the good prognosis group(all P＞0.05).Compared with the good prognosis group,the poor prognosis group had significantly older age and higher proportion of patients with diabetes,NIHSS score at admission,proportion of patients with poor collateral circulation,and PIV(all P＜0.05).Moreover,the proportion of men in the poor prognosis group was lower than that in the good prognosis group(P=0.039).There was a statistically significant difference between the good prognosis group and the poor prognosis group in the Fazekas classification of white matter lesions(P＜0.01).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.345,95％CI 1.081-1.674,P=0.008),poor collateral circulation(OR,3.903,95％CI 1.061-14.355,P=0.040),and high PIV(OR,1.011,95％CI 1.005-1.017,P＜0.01)were independent risk factors of poor prognosis in patients with APACI.The AUC for predicting poor prognosis in patients with APACI through combining PIV,collateral circulation and NIHSS score at admission was 0.911(95％CI 0.857-0.950,P＜0.01),which is greater than using poor collateral circulation or NIHSS score at admission alone(both P＜0.05).However,there was no statistically significant difference in AUC between the PIV,collateral circulation and NIHSS score combined predictive model and the PIV(alone)predictive model(P＞0.05).Conclusions High PIV,high BAR,poor collateral circulation,and high NIHSS score at admission were independent risk factors of disease progression in patients with APACI.Combination of these four indices demonstrates relatively high predictive value for disease progression.In addition,high PIV,poor collateral circulation,and high NIHSS score at admission are independent risk factors of poor prognosis in patients with APACI.Joint detection of the three indices may assist in short-term prognosis evaluation of patients with APACI.

Objective To investigate the predictive value of pan-immune-inflammation value(PIV),blood urea nitrogen to albumin ratio(BAR),collateral circulation and National Institutes of Health stroke scale(NIHSS)score for disease progression and short-term prognosis in patients with acute perforating artery cerebral infarction(APACI).Methods Patients with APACI admitted to the Neurology Department of Anhui NO.2 Provincial People's Hospital from January 2019 to October 2024 were retrospectively enrolled in this study.General and clinical data,including age,gender,previous history(hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,drinking history,NIHSS scores at admission were collected.Fasting venous blood samples were collected from the patients within 24 h after admission to detect levels of neutrophils,lymphocytes,monocytes,platelets,blood urea nitrogen,and serum albumin.PIV(PIV=neutrophils × platelets × monocytes/lymphocytes)and BAR were calculated.The location of lesions and Fazekas classification of white matter lesions were evaluated using head MRI and MR angiography at admission.Collateral circulation status was assessed based on CT angiography upon admission.Disease progression was defined through comparing the NIHSS score at 72-hour after admission to the score at admission(an increase of 2 or more points in NIHSS score indicating disease progression).The patients were divided into a progression group and a non-progression group based on the increase in NIHSS score,as aforementioned.Patients follow-up was conducted through phone call or outpatient visits at 90 d after discharge.The modified Rankin scale(mRS)was used to evaluate the prognosis,with a mRS score of 0-2 indicates good prognosis,and a 3-6 indicates poor prognosis.Factors with statistically significant differences in univariate analysis were included in a multivariate Logistic regression analysis to explore the influencing factors of disease progression and poor prognosis in patients with APACI.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each indicator for disease progression and poor prognosis in patients with APACI.Results A total of 165 patients with APACI were enrolled in this study,including 121 males and 44 females,aged 27-86 years,with an average of(61±11)years.Among all patients enrolled,56 patients were included in the progression group and 109 patients in the non-progression group,124 patients showed good prognosis and 41 patients had poor prognosis.No statistically significant differences were found in age,gender,smoking history,drinking history,hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and Fazekas classification of white matter lesions between the progression group and the non-progression group(all P＞0.05).While the NIHSS score at admission,proportion of poor collateral circulation,PIV and BAR in the progression group were significantly higher than those in the non-progression group(all P＜0.05).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.177,95％CI 1.001-1.384,P=0.049),poor collateral circulation(OR,3.107,95％CI 1.216-7.939,P=0.018),high PIV(OR,1.006,95％CI 1.003-1.009,P=0.001),and high BAR(OR,1.610 × 109,95％CI 5.769 × 104-4.494 × 1013,P＜0.01)were independent risk factors of disease progression in patients with APACI.ROC curve analysis results showed that the area under the curve(AUC)of combination of PIV,BAR,collateral circulation and NIHSS score at admission for predicting disease progression in patients with APACI was 0.914(95％ CI0.861-0.952,P＜0.01),which was greater than that of each indicator(all P＜0.05).No statistically significant differences were found in smoking,drinking,hypertension,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and BAR between the poor prognosis and the good prognosis group(all P＞0.05).Compared with the good prognosis group,the poor prognosis group had significantly older age and higher proportion of patients with diabetes,NIHSS score at admission,proportion of patients with poor collateral circulation,and PIV(all P＜0.05).Moreover,the proportion of men in the poor prognosis group was lower than that in the good prognosis group(P=0.039).There was a statistically significant difference between the good prognosis group and the poor prognosis group in the Fazekas classification of white matter lesions(P＜0.01).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.345,95％CI 1.081-1.674,P=0.008),poor collateral circulation(OR,3.903,95％CI 1.061-14.355,P=0.040),and high PIV(OR,1.011,95％CI 1.005-1.017,P＜0.01)were independent risk factors of poor prognosis in patients with APACI.The AUC for predicting poor prognosis in patients with APACI through combining PIV,collateral circulation and NIHSS score at admission was 0.911(95％CI 0.857-0.950,P＜0.01),which is greater than using poor collateral circulation or NIHSS score at admission alone(both P＜0.05).However,there was no statistically significant difference in AUC between the PIV,collateral circulation and NIHSS score combined predictive model and the PIV(alone)predictive model(P＞0.05).Conclusions High PIV,high BAR,poor collateral circulation,and high NIHSS score at admission were independent risk factors of disease progression in patients with APACI.Combination of these four indices demonstrates relatively high predictive value for disease progression.In addition,high PIV,poor collateral circulation,and high NIHSS score at admission are independent risk factors of poor prognosis in patients with APACI.Joint detection of the three indices may assist in short-term prognosis evaluation of patients with APACI.

Objective:To evaluate the effect of disulfiram on sepsis-associated encephalopathy (SAE) and the relationship with NOD-like receptor family pyrin domain-containing 3 (NLRP3)/caspase-1 signaling pathway in rats.Methods:Forty-five SPF healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-220 g, were divided into 3 groups ( n=15 each) using a random number table method: sham operation group, SAE group, and SAE+ disulfiram group (SAE+ DSF group). The SAE model was established by by using cecal ligation and puncture in anesthetized rats. SAE+ DSF group received an intraperitoneal injection of 50 mg/kg disulfiram 4 h before the cecal ligation and puncture. The survival status of rats was recorded within 72 h after surgery. Their neurobehavioral scores were assessed and recorded on days 1-3 after surgery. On the 3rd day after surgery, novel object recognition test (cognitive index) and open field test (activity distance and time in the central area) were conducted sequentially. Following the behavioral testing, the rats were anesthetized, and their hippocampi were dissected and isolated to observe the pathological changes in the hippocampal region (using HE staining) and to determine the expression of NLRP3 and caspase-1 (by Western blot) and the expression of interleukin-1beta (IL-1β), IL-18 and tumor necrosis factor-alpha (TNF-α) mRNA (by fluorescent quantitative polymerase chain reaction). Results:Compared with Sham group, the 72-h survival rate and postoperative neurobehavioral scores were significantly decreased, the activity distance and time in the central area of the open field were shortened, and the cognitive index was decreased, the expression of NLRP3, caspase-1 and IL-1β, IL-18 and TNF-α mRNA was up-regulated ( P<0.05), and the pathological damage was marked in the hippocampus in SAE group ( P<0.05). Compared with SAE group, postoperative neurobehavioral scores were significantly increased, the activity distance and time in the central area of the open field were prolonged, the cognitive index was increased, and the expression of NLRP3 and caspase-1 and IL-1β, IL-18 and TNF-α mRNA was down-regulated ( P<0.05), no significant change was found in the 72-h survival rate ( P>0.05), and the pathological damage to the hippocampus was significantly alleviated in SAE+ DSF group. Conclusions:Disulfiram can alleviate SAE in rats, and the mechanism may be related to the inhibition of the NLRP3/caspase-1 signaling pathway.

Objective To evaluate the risk of bias and reporting quality in randomized controlled trials(RCTs)of the Chinese medicine injection for acute cerebral infarction in the last five years.Methods RCTs literature on Chinese medicine injection in the treatment of acute cerebral infarction was systematically searched in CNKI,Wanfang Data,VIP,China Biology Medicine Database(CBM),PubMed,Embase and Cochrane Library from April 20,2018 to April 20,2023.The risk of bias and reporting quality of included RCTs were evaluated using the Cochrane Risk of Bias Tool(ROB 1.0)and CONSORT-CHM Formulas 2017,respectively.Results A total of 4 301 articles were retrieved,and 408 RCTs were included according to inclusion and exclusion criteria.The ROB evaluation results showed that the the majority of studies were rated as having an unclear risk of bias due to the lack of reporting on allocation concealment,blind method,trial registration information,and funding sources.The evaluation results of CONSORT-CHM Formulas 2017 showed that the number of reported papers of 17 items was greater than or equal to 50%,and the number of reported papers of 25 items was less than 10%,and most of the RCTs did not show the characteristics of TCM syndrome differentiation and treatment.Conclusion The quality of Chinese medicine injection in the treatment of acute cerebral infarction RCTs is generally low.It is recommended that researchers refer to the methodology design of RCTs and international reporting standards,improve the trial design,standardize the trial report,and highlight the characteristics of TCM syndrome differentiation and treatment.

Objective:To evaluate the relationship between the occipitocervical angle(basilar vertebral angle [O-C 2 angle], mento-pharyngeal angle [M-P angle], and cervical range of motion [CROM]) and difficult airway after occipitocervical fusion surgery in the patients. Methods:This was a retrospective study. The clinical data from patients who underwent occipitocervical fusion surgery at our hospital from March 2018 to March 2023 were retrospectively collected. Preoperative and last follow-up airway assessment data and cervical lateral X-rays were collected to measure the O-C 2 angle, M-P angle and CROM. Patients were divided into negative group (Mallampati grade Ⅰ or Ⅱ, suggesting no difficulty in intubation) and positive group (Mallampati grade Ⅲ or Ⅳ, suggesting possible difficulty in intubation) based on the last follow-up modified Mallampati classification. Results:A total of 53 patients were finally included, with 18 cases in positive group and 35 in negative group. There were no statistically significant differences in the O-C 2 angle and CROM between preoperative and last follow-up in the 53 patients ( P>0.05), and the M-P angle was significantly decreased at the last follow-up compared with that before operation ( P<0.05). Compared with negative group, O-C 2 angle and M-P angle were significantly decreased at the last follow-up ( P<0.05), and no significant change was found in CROM in positive group ( P<0.05). Compared with that before operation, the M-P angle was significantly decreased at the last follow-up in both groups, and the O-C 2 angle was significantly decreased at the last follow-up in positive group ( P<0.05). The areas under the receiver operating characteristic curves of O-C 2 angle, M-P angle and CROM in predicting difficult airway were 0.895, 0.888 and 0.519 respectively. Conclusions:The decrease in the O-C 2 angle and M-P angle after occipitocervical fusion surgery can increase the risk of difficult airway, and both can be used for airway assessment in the patients undergoing this kind of surgery.

Objective:Some patients receiving entecavir (ETV) or tenofovir alafenamide fumarate (TAF) monotherapy may develop low-level viremia. Therefore, this study aims to observe whether switching to tenofovir alafenamide fumarate (TMF) monotherapy can further improve the efficacy of antiviral therapy in patients with chronic hepatitis B with low-level viremia.Methods:Patients with chronic hepatitis B who received ETV or TAF monotherapy for over one year were chosen. The serum HBV DNA of all patients from initiation to end fluctuated between 20-2 000 IU/ml were observed. All patients who voluntarily switched to TMF to continue antiviral treatment and completed a comprehensive examination at least once every six months were selected. The primary outcome measure was the undetectable rate of HBV DNA following six and twelve months of TMF treatment, and the secondary outcome measures were the incidence of renal tubular injury and dyslipidemia. Two independent sample t-tests or U-tests were used to compare the intergroup measurement data. The intergroup comparison of count data was performed using the χ2 test or Fisher's exact probability method. Results:A total of 73 patients were included, of which 47 received ETV and 26 received TAF treatment. Among them, 33 cases were hepatitis B e antigen (HBeAg)-positive and 40 were HBeAg-negative. 69.9% (51/73) and 74.0% (54/73) of patients had HBV DNA<20 IU/ml following switching to TMF treatment for six and twelve months, respectively. Compared with HBeAg-positive patients, HBeAg-negative patients who switched to TMF treatment had a higher proportion of complete virological response (19/33 vs. 32/40, P=0.038; 18/33 vs. 36/40, P<0.001). The abnormal rate of urinary β2-microglobulin was 16.4% (12/73) after twelve months of treatment, and the proportion of patients with urinary 2-microglobulin that exceeded three times the upper limit of normal was 6.8%. The proportion of blood phosphate below the normal lower limit was 19.2% (14/73). The total cholesterol and low-density lipoprotein cholesterol levels rose compared to before therapy; however, the difference was not statistically significant. Conclusion:CHB patients receiving treatment with ETV or TAF develop low-level viremia. Therefore, switching to TMF can help most patients achieve a complete virological response and possesses good patient tolerance.

Objective:Some patients receiving entecavir (ETV) or tenofovir alafenamide fumarate (TAF) monotherapy may develop low-level viremia. Therefore, this study aims to observe whether switching to tenofovir alafenamide fumarate (TMF) monotherapy can further improve the efficacy of antiviral therapy in patients with chronic hepatitis B with low-level viremia.Methods:Patients with chronic hepatitis B who received ETV or TAF monotherapy for over one year were chosen. The serum HBV DNA of all patients from initiation to end fluctuated between 20-2 000 IU/ml were observed. All patients who voluntarily switched to TMF to continue antiviral treatment and completed a comprehensive examination at least once every six months were selected. The primary outcome measure was the undetectable rate of HBV DNA following six and twelve months of TMF treatment, and the secondary outcome measures were the incidence of renal tubular injury and dyslipidemia. Two independent sample t-tests or U-tests were used to compare the intergroup measurement data. The intergroup comparison of count data was performed using the χ2 test or Fisher's exact probability method. Results:A total of 73 patients were included, of which 47 received ETV and 26 received TAF treatment. Among them, 33 cases were hepatitis B e antigen (HBeAg)-positive and 40 were HBeAg-negative. 69.9% (51/73) and 74.0% (54/73) of patients had HBV DNA<20 IU/ml following switching to TMF treatment for six and twelve months, respectively. Compared with HBeAg-positive patients, HBeAg-negative patients who switched to TMF treatment had a higher proportion of complete virological response (19/33 vs. 32/40, P=0.038; 18/33 vs. 36/40, P<0.001). The abnormal rate of urinary β2-microglobulin was 16.4% (12/73) after twelve months of treatment, and the proportion of patients with urinary 2-microglobulin that exceeded three times the upper limit of normal was 6.8%. The proportion of blood phosphate below the normal lower limit was 19.2% (14/73). The total cholesterol and low-density lipoprotein cholesterol levels rose compared to before therapy; however, the difference was not statistically significant. Conclusion:CHB patients receiving treatment with ETV or TAF develop low-level viremia. Therefore, switching to TMF can help most patients achieve a complete virological response and possesses good patient tolerance.