To investigate the therapeutic effect and related mechanisms of hordenine on ovalbumin (OVA)-induced allergic rhinitis (AR) in rats, HE and AB-PAS staining were used to detect the improvement of pathological damage to the nasal mucosa induced by hordenine. ELISA was employed to detect the effect of hordenine on OVA-sIgE in serum and IL-4 in the nasal mucosa supernatant of rats. IHC and Western blot experiments were undertaken to examine the effect of hordenine on Th1/Th2 cell balance. Bioinformatics analysis was performed to predict pathways, which were verified by in vivo and in vitro experiments. The experimental results showed that hordenine could alleviate the behavioral manifestations of OVA-induced AR rats, alleviate nasal mucosal pathological damage caused by AR, and reduce the secretion of OVA-sIgE and IL-4. In addition, hordenine could regulate the Th1/Th2 balance. Bioinformatics analysis results showed that the potential pathway of action of hordenine on AR was the phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. The in vivo experimental results showed that the expression of PI3K and p-Akt proteins in the nasal mucosa of the model group rats was significantly increased (P < 0.01), and that the protein expression level was significantly decreased after the administration of hordenine, which was also confirmed by an in vitro experiment. This study suggests that hordenine may regulate Th1/Th2 cell balance through the PI3K/Akt signaling pathway, thereby exerting an alleviating effect on OVA-induced AR.

Objective To explore the clinical efficacy of repeated transcranial magnetic stimulation(rTMS)and acupuncture therapy in the treatment of chronic insomnia disorder(CID)patients.Methods A total of 80 patients with CID,who were treated at Nanchang First Hospital from January 2022 to December 2023,were selected for the study.The patients were randomly divided into control group and treatment group,with 40 cases in each group.The control group patients were treated with dexmedetomidine,while the treatment group patients received rTMS and acupuncture therapy in addition to control group.The treatment course was 4 weeks,and the sleep quality,sleep related indicators,and psychological condition improvement of both groups of patients were observed before and after treatment.Results After treatment,the Pittsburgh sleep quality index scores of both groups of patients decreased(P＜0.05);The sleep latency and number of awakenings were lower than before treatment(P＜0.05),and the total sleep time,sleep efficiency,and proportion of rapid eye movement sleep were higher than before treatment,treatment group showed more significant improvement than control group(P＜0.05).After treatment,the Hamilton anxiety and depression scale scores of both groups of patients decreased compared to before treatment,but there was no statistically significant difference in control group before and after treatment(P＞0.05).However,there was a statistically significant difference in treatment group before and after treatment(P＜0.05).Conclusion The combination of rTMS and acupuncture treatment can significantly improve the sleep quality of CID patients,while also reducing the accompanying symptoms of anxiety and depression.

Background::T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.Methods::Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.Results::The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4 + T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8 + T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8 + T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. Conclusions::Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

Hilar cholangiocarcinoma is the most common extrahepatic malignant tumor in clinic, accounting for about 50%-60% of bile duct tumors. Currently, radical surgical resection is regarded as the best treatment for early hepatic hilar cholangiocarcinoma, but, it’s early lesions have no obvious clinical symptoms. Most patients are already in the advanced stage of the disease when they are admitted to hospital. The surgical resection rate is low, and the 5-year survival rate does not exceed 25%. Locally advanced hepatic hilar cholangiocarcinoma are treated with neoadjuvant chemoradiation therapy followed by surgery, it can prolong survival time of the patient. At the same time, the recurrence rate after surgery can reach 50%-70%, and the cancer easily invades microvessels, lymphatic vessels, peripheral nerves and liver, which is one of the most challenging problems in the field of biliary surgery. Therefore, early diagnosis, perioperative management, adequate and accurate preoperative staging assessment, intraoperative standardized resection, postoperative adjuvant therapy of hilar cholangiocarcinoma, it is of great significance to improve the rate of radical surgical resection and prolong the survival time of patients.

Objective:To investigate the characteristics of distribution and drug resistance of urinary bacteria in the mid-stream urine of patients with infectious stones.Methods:The retrospective study analyzed the clinical data of 254 patients with infectious stones in the First Affiliated Hospital of Guangzhou Medical University from September 2016 to September 2018. All patients were treated with PCNL. Overall, there were 101 male and 153 female patients, with the mean age of(51.5±12.3) years, and the mean stone burden of 1443.5(660.8, 2837.5) mm2. There were 58 (22.8%) patients with hypertension, 17(6.7%) patients with diabetes and 195(76.8%)with hydronephrosis. The mid-stream urine samples were obtained for bacterial culture and susceptibility test, and the results of urine culture and antimicrobial susceptibility were recorded and analyzed.Results:Of 254 patients involved in this study, 89(35.0%) were positive and 165 (65.0%) were negative for urinary bacterial culture of the mid-stream. The proportion of patients with positive urine bacterial culture of the mid-stream who had positive urine leucocytes, positive urine nitrite and postoperative pyrexia were 86.5%(77/89), 64.0%(57/89), 25.8%(23/89), respectively, which was higher than that of patients with negative urine bacterial culture of the mid-stream [50.3%(83/165), 14.5%(24/165), 14.5%(24/165), P<0.05]. Four teen kinds of bacteria were detected from the mid-stream urine, and the three bacteria with the highest detection rate in turn were Escherichia coli of 38.2%(34/89), Proteus mirabilis of 15.7%(14/89), and Pseudomonas aeruginosa of 11.2%(10/89). The results of this study showed that three common bacteria had high resistance to drug including Cefazolin, Cefuroxime, Cefuroxime ester, Ampicillin and Co-trimoxazole (all resistance rate>40%). The resistance rates of Escherichia coli and Pseudomonas aeruginosa to Ciprofloxacin and Levofloxacin were higher than or equal to 40%. The resistance rates of Escherichia coli and Proteus mirabilis to meropenem, imipenem, ertapenem, piperacillin/tazobactam and amikacin were all lower than 10%. In addition, the resistance rates of Escherichia coli to nitrofurantoin and tigecycline and Proteus mirabilis to tobramycin, aztreonam and cefoxitin were all less than 10%. The resistance rates of Pseudomonas aeruginosa to ceftazidime, cefepime, gentamicin and aztreonam were less than 10%. Conclusions:The highest detection rate of urinary bacteria in culture of the mid-stream with infectious stones are Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa, all of which showed high resistance to Ampicillin, Cotrimoxazole, and some cephalosporins. Escherichia coli and Pseudomonas aeruginosa showe high resistance to Ciprofloxacin and Levofloxacin, and all of the three bacteria have low resistance rates to some β-Lactamase inhibitor complex and carbapenems, suggesting a reference for clinical empirical medical treatment.

Objective To investigate the changes in neutrophil immunophenotypes in neonates with late-onset sepsis and their clinical significance.Methods A total of 42 neonates with late-onset sepsis were enrolled prospectively as sepsis group from Children's Hospital of Fudan University from January 2015 to October 2016,which included 26 preterm infants and 16 term infants.Another 33 neonates without infectious diseases consisting of 20 preterm infants and 13 term infants were selected as control group.According to the severity of sepsis,neonates in the sepsis group were further divided into severe (n=11)and mild sepsis (n=31) subgroups.Expression of CD16 and CD62L on neutrophils was measured by flow cytometry to determine the distribution of neutrophil subsets in neonatal peripheral blood.Differences in the distribution of neutrophil subsets between the two groups and two subgroups were compared using Wilcoxon rank-sum test.Multivariate logistic regression analysis was used to investigate the relationship between neutrophil subsets and the severity of neonatal sepsis.Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of neutrophil subsets for the severity of sepsis.Results Four neutrophil subsets were identified in neonatal peripheral blood,including early-stage neutrophils (CD16-/CD62L-),immature neutrophils (CD16-/CD62L+),mature neutrophils (CD16+/CD62L+) and activated neutrophils (CD16+/CD62L-).Activated [preterm:61.1％ (20.2％-79.4％),term:47.6％ (15.2％-70.1％)] and mature neutrophils [preterm:35.7％ (19.9％-75.8％),term:52.0％ (25.6％-82.8％)] were the dominant subsets in the control group.In preterm infants,the proportion of early-stage [3.5％ (1.7％-9.4％) vs 1.9％ (0.6％-4.0％),Z=-2.501,P=0.012] and immature neutrophils [6.3％ (0.7％-45.5％) vs 0.4％ (0.3％-0.7％),Z=-3.878,P＜0.001] were higher,but that of activated neutrophils [8.3％ (2.3％-49.2％) vs 61.1％ (20.2％-79.4％),Z=2.991,P=0.002] were lower in the sepsis group than those in the control group;same differences were found in the absolute counts of each neutrophil subsets.Among term infants,more immature neutrophils were found in the sepsis group than those in the control group [49 (18-200) vs 13 (5-36)/μl,Z=-2.193,P=0.028].The proportion and the absolute counts of early-stage and immature neutrophils in the severe sepsis subgroup were all higher than those in the mild cases [early-stage neutrophils:5.8％ (3.4％-17.8％) vs 3.0％ (1.4％-7.3％),304 (137-1478) vs 158 (53-321)/μl;immature neutrophils:23.0％ (6.3％-47.0％) vs 0.9％ (0.5％-6.8％),1003 (487-2818) vs 85 (18-275)/μl;all P＜0.05].Multivariate logistic regression analysis showed that the proportion of early-stage neutrophils was associated with the severity of sepsis (OR=1.2,95％CI:1.0-1.4,P=0.012).In addition,the diagnostic value of the proportion of early-stage neutrophils for severe sepsis was the highest when the cut-off value was 3.3％,with the area under the ROC curve was 0.7 (95％CI:0.6-0.9),sensitivity of 81.8％ (95％CI:48.2％-97.7％) and specificity of 62.3％ (95％CI:42.2％-78.2％).Conclusions There are four neutrophil subsets in the peripheral blood of neonates and autoactivation of neutrophils may exist.With the onset of sepsis,neutrophil subsets react differently between preterm and term infants.The proportion of early-stage neutrophils may be correlated with the severity of neonatal sepsis,which may have a predictive value for severe sepsis.

Objective To study the pharmacokinetics of raltitrexed using different ways of drug delivery, including femoral venous infusion, hepatic artery perfusion, hepatic artery injection of lipiodol suspension, hepatic artery perfusion followed by embolization with Gelfoam. Methods According to the administration way of raltitrexed, a total of 40 New Zealand rabbit models with VX2 liver tumor were randomly divided into group A (femoral venous perfusion), group B (hepatic arterial perfusion), group C (hepatic artery injection of lipiodol suspension), and group D(hepatic artery perfusion followed by embolization with Gelfoam). Drug concentration in plasma were determined by using LC-MS/MS method and the pharmacokinetic parameters were calculated. Results After administration of raltitrexed, the Tmax was 5 minutes in all 4 groups. In group A, B, C and D, the values were (5.88±1.39), (7.31±2.60), (9.86±5.10) and (7.19±2.27) respectively, with group C having the longest t1/2 value, which was significantly different with that of group A (P＜0.05); the (ng·ml-1·h-1) values were (2 056.40± 139.17), (1 389.21±180.28), (911.84±105.62) and (1 133.41±181.42)respectively, with the value of group A being obviously higher than that of group B, C and D (P＜0.05) and the value of group C being the lowest; the AUC0-t(ng· ml-1·h-1) values were (5 482.72±1 007.07), (4 156.99±1 475.77), (2 785.13±1 107.36) and (3 903.64±947.25) respectively, with the value of group A being remarkably higher than that of group B, C and D (P＜0.05) and the value of group C being the lowest. Conclusion Compared with the femoral vein infusion way, the ways of hepatic artery infusion, hepatic artery lipiodol suspension injection and hepatic artery perfusion followed by embolization with Gelfoam may promote more raltitrexed to deposit in the tumor area, thus, the curative effect is enhanced, the drug concentration in plasma is lowered and the side effects are alleviated.

Primary liver cancer is the fifth most common cancer and the third leading cause of cancer death worldwide.MicroRNAs(miRNAs)are small non-coding RNA molecules that downregulate gene expression by binding to the 3'-untranslated region of target miRNAs.MiRNAs function as tumor sup-pressors or oncogenes by regulating oncogene or tumor suppressor gene expression and their related signaling pathways involved in liver cancers including hepatocellular carcinoma,cholangiocarcinoma,and hepatoblastoma.In this review,we provide a systematic evaluation of the relationship between miRNAs and liver cancers,and describe the potential applications of miRNAs in liver cancer diagnosis and treatment.

Objective To explore the possible mechanism of Jianyi Recipe for improving the function of islet cells from the aspects of synthesis,secretion and inactivation of glucagon-like peptide-1 (GLP-1).Methods The diabetic rat model was established by feeding with high-lipid food combined with injection of streptozotocin (STZ).The rats were randomly divided into model group,Jianyi Recipe group,and normal group.The treatment for the rats lasted for 4 weeks.The blood glucose level was detected by the rapid blood glucose meter.The plasma levels of GLP-1 and insulin were detected by Luminex liquid phase protein chip technology.Pancreatic duodenal homeobox-1 (PDX-1) mRNA expression level was detected by quantitative real-time fluorescence polymerase chain reaction (PCR).The level of GLP-1 in ileum L cells was detected by immunohistochemistry,and dipeptidyl peptidase Ⅳ (DPP-Ⅳ)level was detected by enzyme-linked immunosorbent assay.Results Jianyi Recipe could decrease the levels of fasting blood glucose and postprandial glucose (P ＜ 0.05),promote the secretion of insulin (P ＜ 0.05),and increase PDX-1 mRNA expression level in the pancreas of the diabetic rats.Compared with the model group,plasma GLP-1 level,and ileal GLP-1 positive expression area and integrated optical density were increased (P ＜ 0.05) in Jianyi Recipe group,while the differences of serum DPP-Ⅳ levels were insignificant between the two groups (P＞ 0.05).Conclusion Jianyi Recipe maybe regulate the synthesis and secretion of GLP-1 to promote PDX-1 gene expression and insulin secretion,so as to reduce blood glucose in diabetic rats.