[Treatment of migrated lumbar intervertebral disc herniation by percutaneous spinal endoscopy through bone tunnel].

OBJECTIVE: To investigate the clinical effect of percutaneous endoscopic lumbar discectomy (PELD) through bone tunnel in the treatment of migrated lumbar intervertebral disc herniation. METHODS: The clinical data of 42 patients with migrated lumbar intervertebral disc herniation treated through PELD techniques were retrospectively analyzed from October 2015 to December 2018. There were 26 males and 16 females, aged from 39 to 71 years old with a mean of(58.55±7.16) years. There were 7 cases where the affected segment was L3,4, 24 cases of L4,5, and 11 cases of L5S1. According to modified free nucleus pulposus classification, 3 cases of type A1, 6 cases of type A2, 8 cases of type B1, 8 cases of type B2, 6 cases of type C1, and 11 cases of C2. Among these 42 cases, 22 patients were treated with transpedicular approach (transpedicular approach group), 6 cases were type A2, 6 cases were type B2 and 10 cases were type C2, and 20 cases with translaminar approach(translaminar approach group), 3 cases were type A1, 8 cases were type B1, 6 cases were type C1, 2 cases were type B2 and 1 case was type C2. The operation time, intraoperative and postoperative complications of the two groups were recorded, and the pain visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to assess the improvement of the clinical symptoms before surgery, immediately after surgery, and 12 months after surgery, and the modified Macnab evaluation system was used to evaluate the clinical efficacy. RESULTS: The operative time was from 69 to 105 min with a mean of (88.29±9.85) min;and no intraoperative complications such as neurovascular injury or dural tear were occurredin all patients. One case in the transpedicular approach group was changed to general anesthesia and translaminar approach due to local anesthesia intolerance. All the patients were followed up from 13 to 34 months, with a mean of (13.71±3.56) months. VAS and ODI were significantly improved in two groups immediately after surgery and 12 months after surgery (P<0.05). According to modified Macnab criteria, 27 cases obtained excellent results, 11 good, 3 fair, and 1 poor. There were no postoperative complications such as lumbar fractures and postoperative infections in the follow-up patients. CONCLUSION: For migrated intervertebral disc herniation, the modified nucleus pulposus classification can be used to estimate the precise target before operation, and the reasonable bone tunnel approach can be selected to obtain good results.

Distinct Effects of Ca2+ Sparks on Cerebral Artery and Airway Smooth Muscle Cell Tone in Mice and Humans.

The effects of Ca2+ sparks on cerebral artery smooth muscle cells (CASMCs) and airway smooth muscle cells (ASMCs) tone, as well as the underlying mechanisms, are not clear. In this investigation, we elucidated the underlying mechanisms of the distinct effects of Ca2+ sparks on cerebral artery smooth muscle cells (CASMCs) and airway smooth muscle cells (ASMCs) tone. In CASMCs, owing to the functional loss of Ca2+-activated Cl- (Clca) channels, Ca2+ sparks activated large-conductance Ca2+-activated K+ channels (BKs), resulting in a decreases in tone against a spontaneous depolarization-caused high tone in the resting state. In ASMCs, Ca2+ sparks induced relaxation through BKs and contraction via Clca channels. However, the integrated result was contraction because Ca2+ sparks activated BKs prior to Clca channels and Clca channels-induced depolarization was larger than BKs-caused hyperpolarization. However, the effects of Ca2+ sparks on both cell types were determined by L-type voltage-dependent Ca2+ channels (LVDCCs). In addition, compared with ASMCs, CASMCs had great and higher amplitude Ca2+ sparks, a higher density of BKs, and higher Ca2+ and voltage sensitivity of BKs. These differences enhanced the ability of Ca2+ sparks to decrease CASMC and to increase ASMC tone. The higher Ca2+ and voltage sensitivity of BKs in CASMCs than ASMCs were determined by the ß1 subunits. Moreover, Ca2+ sparks showed the similar effects on human CASMC and ASMC tone. In conclusions, Ca2+ sparks decrease CASMC tone and increase ASMC tone, mediated by BKs and Clca channels, respectively, and finally determined by LVDCCs.

Chloroquine inhibits Ca2+ permeable ion channels-mediated Ca2+ signaling in primary B lymphocytes.

BACKGROUND: Chloroquine, a bitter tastant, inhibits Ca2+ signaling, resulting in suppression of B cell activation; however, the inhibitory mechanism remains unclear. RESULTS: In this study, thapsigargin (TG), but not caffeine, induced sustained intracellular Ca2+ increases in mouse splenic primary B lymphocytes, which were markedly inhibited by chloroquine. Under Ca2+-free conditions, TG elicited transient Ca2+ increases, which additionally elevated upon the restoration of 2 mM Ca2+. The former were from release of intracellular Ca2+ store and the latter from Ca2+ influx. TG-induced release was inhibited by 2-APB (an inhibitor of inositol-3-phosphate receptors, IP3Rs) and chloroquine, and TG-caused influx was inhibited by pyrazole (Pyr3, an inhibitor of transient receptor potential C3 (TRPC3) and stromal interaction molecule (STIM)/Orai channels) and chloroquine. Moreover, chloroquine also blocked Ca2+ increases induced by the engagement of B cell receptor (BCR) with anti-IgM. CONCLUSIONS: These results indicate that chloroquine inhibits Ca2+ elevations in splenic B cells through inhibiting Ca2+ permeable IP3R and TRPC3 and/or STIM/Orai channels. These findings suggest that chloroquine would be a potent immunosuppressant.

Chloroquine Inhibits Ca(2+) Signaling in Murine CD4(+) Thymocytes.

BACKGROUND/AIMS: Bitter-tasting chloroquine can suppress T cell activation by inhibiting Ca(2+) signaling. However, the mechanism of inhibition remains largely unclear. METHODS: In this study, CD4(+) T cells were isolated from the thymus, and the calcium content of CD4(+) thymocytes was measured using fura-2 AM and a TILL imaging system. Pyrazole-3 (Pyr3), thapsigargin (TG), and caffeine were used to assess the effects of chloroquine on the intracellular Ca(2+) content of CD4(+) T cells. RESULTS: In murine CD4(+) thymocytes, chloroquine decreased the TG-triggered intracellular Ca(2+) increase in a dose-dependent manner. In the absence of chloroquine under Ca(2+)-free conditions (0 mM Ca(2+) and 0.5 mM EGTA), TG induced a transient Ca(2+) increase. After restoration of the extracellular Ca(2+) concentration to 2 mM, a dramatic Ca(2+) increase occurred. This elevation was completely blocked by chloroquine and was markedly inhibited by Pyr3, a selective antagonist of transient receptor potential C3 (TRPC3) channel and stromal interaction molecule (STIM)/Orai channel. Furthermore, the TG-induced transient Ca(2+) increase under Ca(2+)-free conditions was eliminated in the presence of chloroquine. Chloroquine also blocked the dialyzed inositol-1,4,5-trisphosphate (IP3)-induced intracellular Ca(2+) increase. However, chloroquine was not able to decrease the caffeine-induced Ca(2+) increase. CONCLUSION: These data indicate that chloroquine inhibits the elevation of intracellular Ca(2+) in thymic CD4(+) T cells by inhibiting IP3 receptor-mediated Ca(2+) release from intracellular stores and TRPC3 channel-mediated and/or STIM/Orai channel-mediated Ca(2+) influx.

Liver stiffness measurement-based scoring system for significant inflammation related to chronic hepatitis B.

OBJECTIVES: Liver biopsy is indispensable because liver stiffness measurement alone cannot provide information on intrahepatic inflammation. However, the presence of fibrosis highly correlates with inflammation. We constructed a noninvasive model to determine significant inflammation in chronic hepatitis B patients by using liver stiffness measurement and serum markers. METHODS: The training set included chronic hepatitis B patients (n = 327), and the validation set included 106 patients; liver biopsies were performed, liver histology was scored, and serum markers were investigated. All patients underwent liver stiffness measurement. RESULTS: An inflammation activity scoring system for significant inflammation was constructed. In the training set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.964, 91.9%, and 90.8% in the HBeAg(+) patients and 0.978, 85.0%, and 94.0% in the HBeAg(-) patients, respectively. In the validation set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.971, 90.5%, and 92.5% in the HBeAg(+) patients and 0.977, 95.2%, and 95.8% in the HBeAg(-) patients. The liver stiffness measurement-based activity score was comparable to that of the fibrosis-based activity score in both HBeAg(+) and HBeAg(-) patients for recognizing significant inflammation (G ≥3). CONCLUSIONS: Significant inflammation can be accurately predicted by this novel method. The liver stiffness measurement-based scoring system can be used without the aid of computers and provides a noninvasive alternative for the prediction of chronic hepatitis B-related significant inflammation.

Enhanced HBsAg synthesis correlates with increased severity of fibrosis in chronic hepatitis B patients.

BACKGROUND AND AIMS: Little is known about whether low serum HBsAg levels result from impaired HBsAg synthesis or a reduced number of hepatocytes caused by advanced liver fibrosis. Therefore, we investigated the capacity for HBsAg synthesis in a cross-sectional cohort of treatment-naïve chronic hepatitis B patients. METHODS: Chronic hepatitis B patients (n = 362) were enrolled; liver biopsies were performed and liver histology was scored, and serum HBsAg and HBV DNA levels were investigated. In the enrolled patients, 183 out of 362 have quantitative serum HBsAg levels. Tissue HBsAg was determined by immunohistochemistry. RESULTS: A positive correlation between serum HBsAg and HBV DNA levels was revealed in HBeAg(+) patients (r = 0.2613, p = 0.0050). In HBeAg(+) patients, serum HBsAg and severity of fibrosis were inversely correlated (p = 0.0094), whereas tissue HBsAg levels correlated positively with the stage of fibrosis (p = 0.0280). After applying the mean aminopyrine breath test as a correction factor, adjusted serum HBsAg showed a strong positive correlation with fibrosis severity in HBeAg(+) patients (r = 0.5655, p<0.0001). The adjusted serum HBsAg values predicted 'moderate to severe' fibrosis with nearly perfect performance in both HBeAg(+) patients (area under the curve: 0.994, 95% CI: 0.983-1.000) and HBeAg(-) patients (area under the curve: 1.000, 95% CI: 1.000-1.000). CONCLUSIONS: Although serum HBsAg levels were negatively correlated with fibrosis severity in HBeAg(+) patients, aminopyrine breath test-adjusted serum HBsAg and tissue HBsAg, two indices that are unaffected by the number of residual hepatocytes, were positively correlated with fibrosis severity. Furthermore, adjusted serum HBsAg has an accurate prediction capability.