[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

ObjectiveTo investigate the pharmacological action and mechanism of Shuangshenling granules in treating chronic renal failure in rats，providing laboratory data to support clinical application of Shuangshenling granules. MethodSD rats （150-180 g），half males and half females in number，were used，with ten rats designated as the normal group，ten as the sham operation group，and the remaining rats undergoing chronic renal failure modeling induced by 5/6 nephrectomy. Two weeks after operation，serum creatinine （SCr） and blood urea nitrogen （BUN） levels were measured via orbital blood sampling to select successful model rats. Based on SCr values，the rats were evenly divided into the model group，Shenshuaining positive group （0.84 g·kg^-1·d^-1），and high，medium，and low dose groups of Shuangshenling granules （4.8，2.4，1.2 g·kg^-1·d^-1），with ten animals in each group. Each treatment group received drugs at 10 mL·kg^-1 via intragastric administration once daily for six weeks. At 2，4，6 weeks after administration，SCr，BUN，24-hour urine volume，total urinary protein （UTP），urinary creatinine （UCr），creatinine clearance rate （CCr），serum albumin （SAlb），and total serum protein （STP） were measured. Following the experiment，kidney tissues were dissected for pathological examination. The expression levels of autophagy-related proteins，including PTEN-induced kinase 1 （PINK1），E3 ubiquitin-protein ligase parkin （Parkin），and microtubule-associated protein 1 light chain 3B （LC3B），were detected by immunofluorescence. ResultCompared with the normal group，the model group exhibited significantly increased levels of SCr，BUN，24-hour urine volume，UTP，and UCr （P<0.01），and decreased levels of SAlb and STP （P<0.01）. CCr showed an initial increase followed by a decrease. Histopathological results revealed glomerular hyperplasia and atrophy，with varying degrees of mesangial cell reduction，blood stasis in the glomeruli，and significant widening of Bowman's capsule. Visceral parietal layer cells were displaced or absent，leading to incomplete and damaged glomeruli. A large number of protein casts were present in the proximal and distal convoluted tubules，with reduced and displaced cells，swelling in some tubules，and interstitial inflammatory exudation predominantly comprising lymphocytes and a small number of neutrophils. Compared with the model group，all dose groups of Shuangshenling granules significantly reduced levels of SCr，BUN，24-hour urine volume，UTP，and UCr （P<0.05，P<0.01） and increased SAlb and STP levels （P<0.01） at 2，4，and 6 weeks after administration. The three dose groups also improved CCr and alleviated renal pathological injury in varying degrees at 2-6 weeks after administration. Immunofluorescence results showed that the expression levels of PINK1，Parkin，and LC3B were significantly reduced in the model group compared with the normal group，whereas all dose groups of Shuangshenling granules significantly upregulated the expression levels of PINK1，Parkin，and LC3B compared with the model group. ConclusionShuangshenling granules significantly improved renal function and pathological injury in rats with chronic renal failure，likely through the upregulation of PINK1-mediated autophagy.

Objective Neuromuscular electrical stimulation(NMES)-evoked kinesthetic information in muscle spindle can be purely extracted from the mixed motor and sensory afferents using Ischemic nerve block(INB).This study aims to investigate the somatosensory cortical response evoked by NMES activating muscle spindle afferents in forearm.Methods All subjects performed four experimental tasks designed according to a 2×2 factors,including one factor of the INB state(without INB and within INB)and the other of the stimulation intensity(above and below motor threshold).During the experiment,we recorded EEG data with 64 channels and then beta event-related desynchronization(Beta ERD)were utilized quantize somatosensory cortical excitability evoked by the tasks.The subjective perception about the sensation and movement of the right hand were evaluated by a psychophysical test after the right wrist was performed by INB.Results INB significantly reduced beta ERD on the contralateral somatosensory cortex evoked by NMES above the motor threshold,and there was significant difference of NMES-evoked beta ERD values on the contralateral somatosensory cortex between above and below motor threshold.Meanwhile,contralateral dominance of NMES-evoked beta ERD on the somatosensory cortex was transferred to ipsilateral hemisphere under INB.Conclusion INB can significantly reduce NMES-evoked somatosensory cortical response above motor threshold and decrease cortical perception on the stimulus intensity,which may be due to INB resulting in rapid functional reorganization of somatosensory cortex.

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

‍ ObjectiveTo investigate the value of preoperative fibrosis 4 score （FIB-4） combined with prognostic nutritional index （PNI） in predicting recurrence after radiofrequency ablation （RFA） for early-stage hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for the clinical data of 365 patients with the initial diagnosis of early-stage HCC who underwent RFA at Tianjin Third Central Hospital from January 2013 to December 2017， and a statistical analysis was performed for recurrence and survival. The receiver operating characteristic （ROC） curve was plotted for FIB-4 and PNI with postoperative tumor recurrence as the positive event， and their optimal cut-off values were selected. FIB-4 and PNI were graded and combined as FIB-4-PNI score， based on which the patients were divided into 0-point group with 207 patients， 1-point group with 93 patients， and 2-point group with 65 patients. The chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier survival analysis and the log-rank test were used to compare the recurrence-free survival （RFS） and overall survival （OS） between groups， and the Cox regression model was used to investigate the influencing factors for RFS and OS. ResultsThe 1-， 3-， and 5-year RFS rates of all patients were 79.2%， 49.8%， and 34.3%， respectively， with a median RFS of 35 months， while the 1-， 3-， and 5-year OS rates of all patients were 98.9%， 86.9%， and 77.3%， respectively. There were significant differences in cumulative RFS and OS rates between the patients with different levels of FIB-4， PNI， and FIB-4-PNI （RFS rate： χ²=17.890， 29.826， and 32.397， all P<0.001； OS rate： χ²=16.896， 21.070， and 26.121， all P<0.001）. The multivariate Cox regression analysis showed that history of diabetes （hazard ratio ［HR］=1.418， 95% confidence interval ［CI］： 1.046‍ ‍—‍ ‍1.922， P=0.024）， two tumors （HR=1.516， 95%CI： 1.094‍ ‍—‍ ‍2.101， P=0.012）， three tumors （HR=2.146， 95%CI： 1.278‍ ‍—‍ ‍3.604， P=0.004）， FIB-4-PNI 1 point （HR=1.875， 95%CI： 1.385‍ ‍—‍ ‍2.539， P<0.001）， and FIB-4-PNI 2 points （HR=2.35， 95%CI： 1.706‍ ‍—‍ ‍3.236， P<0.001） were independent risk factors for RFS， while two tumors （HR=1.732， 95%CI： 1.005‍ ‍—‍ ‍2.983， P=0.048）， three tumors （HR=3.511， 95%CI： 1.658‍ ‍—‍ ‍7.433， P=0.001）， FIB-4-PNI 1 point （HR=2.094， 95%CI： 1.230‍ ‍—‍ ‍3.565， P=0.006）， and FIB-4-PNI 2 points （HR=3.908， 95%CI： 2.306‍ ‍—‍ ‍6.624， P<0.001） were independent risk factors for OS. ConclusionFIB-4-PNI score can be used as an independent predictive factor for recurrence and overall survival time after RFA for early-stage HCC， and it can be combined with tumor features to predict postoperative recurrence and survival.

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Objective To investigate the level of glycosylated albumin (GA) in liver cirrhosis patients with different Child-Pugh classes and its application value in predicting liver function. Methods A total of 486 patients with liver cirrhosis who were hospitalized in Tianjin Third Central Hospital from January 1 to December 31, 2019, were enrolled, among whom 227 patients had liver cirrhosis without diabetes and 259 patients had liver cirrhosis with diabetes. The patients were divided into groups according to Child-Turcotte-Pugh (CTP) score, and fasting blood glucose, glycosylated hemoglobin, and percentage of GA (GA%) were measured. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between three groups, and the Dwass-Steel-Critchlow-Fligner test was used for further comparison between two groups. Scatter plots and fitting curves were plotted for CTP score and GA% to evaluate the association between them and calculate the cut-off value. Results For the cirrhosis patients without diabetes, there were significant differences between the patients with different Child-Pugh classes in GA% ( χ 2 =24.809, P < 0.001), fasting blood glucose ( χ 2 =11.899, P =0.003), and glycosylated hemoglobin ( χ 2 =13.607, P =0.001); further pairwise comparison showed that there was a significant difference in GA% between Child-Pugh class A/B liver cirrhosis patients without diabetes and Child-Pugh class C liver cirrhosis patients ( P < 0.05), Child-Pugh class A patients had a significantly higher level of fasting blood glucose than Child-Pugh class B patients ( P < 0.05), and Child-Pugh class A patients had a significantly higher level of glycosylated hemoglobin than Child-Pugh class B/C patients ( P < 0.05). For the patients with liver cirrhosis and diabetes, there were significant differences between the patients with different Child-Pugh classes in GA% ( χ 2 =10.734, P =0.005) and fasting blood glucose ( χ 2 =16.295, P < 0.001); further pairwise comparison showed that Child-Pugh class C liver cirrhosis patients with diabetes had a significantly lower GA% than Child-Pugh class A/B patients ( P < 0.05) and Child-Pugh class A patients had a significantly lower fasting blood glucose level than Child-Pugh class B patients ( P < 0.05). The fitting curve showed that GA% increased with the increase in CTP score in the liver cirrhosis patients without diabetes, reached the highest value at the CTP score of 6.5, and then started to decrease, with the lower value at the CTP score of 11.5, which showed a curvilinear relationship; in the liver cirrhosis patients with diabetes, GA% first increased and then decreased with the increase in CTP score, with a cut-off value of 8. Conclusion GA% first increases and then decreases along with the progression of liver cirrhosis. There is a significant difference in GA between liver cirrhosis patients with different Child-Pugh classes, suggesting that the reduction in GA is closely associated with liver function decompensation in end-stage liver cirrhosis.

Intestinal flora imbalance plays a certain role in the development and progression of liver cancer, while probiotics have a certain impact on liver cancer, both of which are the focus of clinical research. This article introduces the mechanism of action of intestinal flora imbalance in the pathogenesis of liver cancer and the preventive effect of probiotics against liver cancer. Intestinal flora imbalance can participate in the pathological process of liver cancer by activating Toll-like receptor 4, regulating the level of metabolites, producing endotoxin, and inducing bacterial translocation and intestinal bacterial overgrowth, while probiotics can effectively prevent liver cancer by maintaining enterohepatic circulation, enhancing immune function, promoting the reproduction of intestinal probiotics, and reducing the toxicity of carcinogens, which can be further studied as the focus of subsequent liver cancer prevention in clinical practice.

Objective:To analyze the risk factors of death within two years of the patients with liver cirrhosis after transjugular intrahepatic portosystemic shunt(TIPS), and to explore the predictive value of 6 common clinical evaluation systems on the risk of death after TIPS.Methods:TIPS clinical data from 132 patients with liver cirrhosis were analyzed retrospectively. According to the 2-year clinical outcome after TIPS, the patients were divided into the death group and the survival group. Logistic regression was used to analyze the risk factors of death within 2 years after TIPS. According to the scores of CTP, MELD, MELD Na, BioCliM, FIB-4, and ALBI evaluation systems, the prediction efficiency of death risk of the six evaluation systems was evaluated by using the receiver operating characteristic (ROC) curves and the area under the curve (AUC).Results:During the 2-year follow-up period after TIPS, the age, urea nitrogen level, platelet count, and proportion of hepatic encephalopathy in the death group were higher than those in the survival group one month after TIPS, and the serum sodium level was lower than those in the survival group (all P<0.05). Multivariate analysis showed that the elderly and hepatic encephalopathy one month after operation were independent risk factors for death (all P<0.05). At 1 week after the surgery, there were significant differences in CTP, MELD, and MELD-Na scores between the survival group and the death group (all P<0.05). One week after operation, the AUC of ROC of CTP, MELD, MELD-Na, and ALBI scores were 0.685, 0.721, 0.805, and 0.658 respectively, and the optimal critical values were 8.5, 12.99, 14.51 and -1.52 respectively. Conclusions:The elderly and the occurrence of hepatic encephalopathy one month after TIPS are independent risk factors for the death of liver cirrhosis patients after TIPS. The evaluation of CTP, MELD, MELD-Na, and ALBI one week after TIPS can predict the death risk of decompensated liver cirrhosis patients within 2 years after TIPS, and MELD-Na has the best predictive effect.