Objective To investigate the efficacy and safety of different optimal therapy strategies for hepatits B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients with suboptimal response to peginterferon-α-2a (peg-IFN-α-2a) at 24 weeks.Methods This open-label,single-center and prospective clinical observational study was conducted in Department of Infectious Diseases at Shanghai Changhai Hospital between January 2009 and December 2011.The cases of HBeAg-positive CHB with suboptimal response to peg-IFN-α-2a at week 24 were enrolled.Based on virological markers and patient preference,patients were treated with either peg-IFN-α-2a add-on adefovir dipivoxil (ADV) or switch-to telbivudine (LdT).Hepatitis B virus (HBV) virological and serological data were collected at week 12,24 and 48 after the initiation of optimal therapy.Adverse reactions were also monitored.Therapeutic efficacy was compared between two groups of patients before and after treatment by x2 test.Kruskall Wallis test and Mann-Whitney test were used for analysis of continuous variables.Results Among 193 HBeAg positive CHB patients treated with interferon,67 had suboptimal response and were enrolled.Forty five cases received peg IFN-α-2a add-on ADV treatment and 22 cases received switch-to LdT treatment.After 48 weeks of optimized therapy,the total tBeAg seroconversion rate was 25.3 ％.The rates of HBeAg loss,HBV DNA negative and alanine aminotransferase normalization were 26.8％,73.1％ and 83.5％,respectively.The peg-IFN-α-2a switch-to LdT strategy had better HBV DNA inhibition efficiency compared with the peg-IFN-α-2a add-on ADV strategy at week 12,24 and 48 (P=0.00,0.00 and 0.01,respectively).However,there was no significant difference of HBV DNA negative rate between two groups at week 48 (x2 =0.01,P=0.89).The obviously intolerable adverse reaction was not reported in two optimized strategy groups.Conclusions The 48-week optimized treatment for HBeAg positive CHB with suboptimal response to peg-IFN-α-2a at week 24 could achieve a higher HBeAg seroconversion rate.The switch-to LdT strategy may have better HBV DNA inhibition efficiency.Both strategies show satisfactory safety and tolerance.

Objective To investigate the dynamic changes of microglial polarization at the perihe-matoma area and provide timepoint evidence for interventing microglial polarization as well as studying the polarization mechanism after intracerebral hemorrhage ( ICH ) . Methods Healthy male Sprague Dawley (SD) rats were randomly divided into sham group,ICH-4 h,1 d,3 d,7 d and 14 d groups with 6 in each group. The rats in ICH groups were injected collagenase VII-s into the caudate nucleus to establish the in-tracerebral hematoma model and rats in sham operated group were treated with the same amount of saline. The brains were taken at 4 h,1 d,3 d,7 d,14 d in the ICH group,1 d in sham group. Microglia typeⅠ( M1, CD11b++CD86+) and microglia typeⅡ( M2,CD11b++Arg-1+) were examined by immunofluorescence and the number of M1 and M2 around hematoma were analyzed. Results ( 1) The M1 and M2 were both ob-served at 4 h after ICH and a small quantity of branches were still presented on M1. ( 2) M1 took the main position in acute stage (1~3 d),early subacute stage(3~7 d) and chronic stage (>14 d) after ICH.The number of M2 was elevated transiently in superacute (<24 h) and late subacute stage (7 d).The number of M2 (31.40±1.69) was more than M1 (21.43±1.81) at 4 h after ICH ( t=- 4.085, P=0.002),and the number of M2 (116.25±5.06) significantly exceeded M1 (85.75±7.32) again on day 7 ( t=-0.690, P=0.001). Conclusion M1 is in a dominant position in acute,early subacute and chronic stages after ICH;M2 is dominant in superacute and late subacute stages. Investigating the mechanism of M2 formation at acute period ( such as 4 h) or late subacute stage ( such as 7 d) ,and inhibiting M1 formation in the early subacute stage ( 1~3 d) have important significance for clinical treatment of ICH.

ObjectiveTo investigate the effects of the imbalance between regulatory T cells (Treg) and T helper 17 cells (Th17) in patients with chronic hepatitis B virus (HBV) infection.MethodsThe serum concentration of Treg/Th17 differentiation-related cytokines in 34 patients with chronic hepatitis B (CHB),20 patients with HBV related acute on chronic liver failure (ACHBLF),and 20 healthy controls (NC) were measured by enzyme-linked immunosorbent assay (ELISA) and proportion of peripheral Th17 and Treg cells were analyzed by flow cytometry.Numeration data was analyzed by Fisher's exact propability method and measurement data was tested by one-factor analysis of variance or Turkey multiple comparison.Results The levels of Th17 differentiation-related cytokines,II-1β (3.97±2.85) pg/mL,IL-6 (12.75±-8.87) pg/mL,and IL-21 (360.0±335.7) pg/ mL in patients with ACHBLF were significantly increased than those in NC,which were (1.87 ±0.94) pg/mL(q=4.559,P＜0.01),(5.28±0.72) pg/mL(q=7.309,P＜0.01) and (46.68±20.17) pg/mL(q=6.946,P＜0.01 ),respectively.The proportion of Th17 increased markedly in patients with ACHBLF than that in NC(q=3.972,P＜0.05).However,compared to NC and patients with ACHBLF,the Treg differentiation-related cytokine,TGF-β,in patients with CHB,increased significantly (q=4.536 and 5.323,respectively; both P＜0.01).And the population of Treg also increased markedly in CHB patients.The level of IL-17A which was the characteristic effector cytokine of Th17 was the highest in patients with ACHBLF.The peripheral Th17 cell proportion was positively correlated with the level of serum total bilirubin in patients with ACHBLF (γ=0.74,P＜0.01).Conclusions Th17 and Treg imbalance including cytokine profiles and cell numbers exists in patients with chronic HBV infection.The Th17 are active in patients with ACHBLF and Treg are active in patients with CHB.

Objective:To evaluate the clinical efficacy of a single-session implantation of spinal cord electrical stimulation with neurophysiological monitoring a spinal cord electrical stimulator under general anesthesia with neurophysiological monitoring for the treatment of high-risk diabetic foot.Methods:The clinical data of seven patients with high-risk diabetic foot who underwent spinal cord electrical stimulation in neurosurgery ward nine of Tianjin Huanhu Hospital from May 2022 to May 2023 were collected. The operation was performed under general anesthesia with the "C" arm X ray machine guidance and neurophysiological monitoring. The arterial diameter and peak flow rate of lower extremity, lower extremity skin temperature (calf skin temperature, foot skin temperature), visual analog scale (VAS), continuous distance of movement, blood glucose level and toe wound were compared between patients before and after surgery.Results:A total of seven patients with high-risk diabetic foot were included. The diameters and peak flow rates of femoral artery, popliteal artery, anterior tibial artery, posterior tibial artery and dorsal foot artery in both lower limbs were significantly improved after surgery. All patients had different degrees of lower limb pain before operation. After operation, VAS score decreased significantly (1.1±0.9 vs. 6.8±3.4), the pain was significantly relieved, and the calf skin temperature and foot skin temperature were significantly higher than those before surgery [calf skin temperature (℃): 33.3±0.9 vs. 30.9±0.7, foot skin temperature (℃): 31.4±0.8 vs. 29.1±0.6], fasting blood glucose and postprandial blood glucose were significantly lower than those before surgery [fasting blood glucose (mmol/L): 7.6±1.4 vs. 10.5±1.2, postprandial blood glucose (mmol/L): 9.3±2.3 vs. 13.5±1.1], the differences were statistically significant (all P < 0.01). The lower limb movement of all seven patients was significantly improved after surgery, including one patient who needed wheelchair travel before surgery, and one patient who had intermittent claudication before surgery. Among them, one patient needed wheelchair travel and one patient had intermittent claudication before surgery. All patients could walk normally at 2 weeks after operation. Among the seven patients, two patients had the diabetic foot wound ulceration before surgery, which could not heal for a long time. One month after surgery, blood flow around the foot wound recovered and the healing was accelerated. The wound was dry and crusted around the wound, and the wound healed well. Conclusion:For diabetic high-risk foot patients who are intolerant to diabetic peripheral neuralgia and local anesthesia spinal cord electrical stimulation test, one-time implantation of spinal cord electrical stimulator under general anesthesia under neurophysiological monitoring can effectively alleviate peripheral neuralgia and other diabetic foot related symptoms, improve lower limb blood supply, and reduce the risk of toe amputation. Clinical practice has proved the effectiveness of this technique, especially for the early treatment of diabetic high-risk foot patients.