Safety of nighttime elective hepatectomy for hepatocellular carcinoma patients: a retrospective study.

Purpose: This study aimed to investigate whether nighttime elective surgery influenced the short-term outcomes and prognosis of hepatocellular carcinoma (HCC) patients. Methods: The 1,339 HCC patients who underwent hepatectomy were divided into the daytime surgery group (8 a.m.-6 p.m., n = 1,105) and the nighttime surgery group (after 6 p.m., n = 234) based on the start time of surgery. The 1:2 propensity score matching (PSM) analysis was used to control confounding factors. The short-term outcomes of HCC patients in the 2 groups were compared before and after PSM. Factors associated with major complications (Clavien-Dindo grade, ≥III) and textbook oncologic outcomes (TOO) were separately identified by multivariable logistic regression based on variables screened via least absolute shrinkage and selection operator (LASSO). The Kaplan-Meier method was used to analyze overall survival (OS) and recurrence-free survival (RFS). Results: TOO was achieved after surgery in 897 HCC patients. HCC patients in the nighttime surgery group had a higher body mass index (P = 0.010). After 1:2 PSM, the baseline characteristics of patients between the 2 groups were similar. Short-term outcomes in HCC patients were comparable both before and after PSM (all Ps > 0.05), as were TOO in the 2 groups before (P = 0.673) and after PSM (P = 0.333). In our LASSO-logistic regression, nighttime surgery was not an independent factor associated with major complications or TOO. Both groups also had similar OS (P = 0.950) and RFS (P = 0.740) after PSM. Conclusion: Our study revealed the safety of nighttime elective hepatectomy for HCC patients.

The effect of switch therapy to tenofovir versus entecavir maintenance on recurrence of hepatocellular carcinoma after surgery (SWITE): study protocol for a randomized controlled trial.

BACKGROUND: Antiviral therapy has been reported to be associated with lower recurrence rate of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV) infection. While entecavir (ETV) and tenofovir disoproxil fumarate (TDF) were both recommended as first-line therapies for HBV patients, recent retrospective studies proposed a lower incidence rate of HCC occurrence or recurrence in those receiving TDF compared ETV. However, the survival benefits of switching to TDF therapy after prolonged ETV treatment before surgery remain uncertain. We delineate the rationale and design of SWITE, a randomized, open-label, phase III trial contrasting TDF switch therapy versus ETV maintenance in HBV-related HCC patients. METHODS AND ANALYSIS: This is a prospective, randomized, controlled, single-center study with two parallel groups of patients with HBV-related HCC who have received long-term ETV therapy before surgery. West China Hospital will enroll 238 patients, randomized in a 1:1 ratio to TDF switch therapy or ETV maintenance after surgery. The primary endpoint of this study is 3-year recurrence free survival (RFS), with the secondary endpoint being 3-year overall survival (OS) after curative surgery of HCC. Safety events will be diligently recorded. ETHICS AND DISSEMINATION: The study protocol aligns with the ethical guidelines of the 1975 Declaration of Helsinki. It was approved by ethics committee of West China Hospital (approval number: 2022-074) and was registered with chictr.org.cn (chiCTR2200057867). Informed consent will be obtained from all participants. The results of this trial will be published in peer-reviewed journals and presentations at national and international conferences relevant to this topic. TRIAL REGISTRATION: chiCTR2200057867 . Date of registration is March 20 2022.

PIVKA-II combined with tumor burden score to predict long-term outcomes of AFP-negative hepatocellular carcinoma patients after liver resection.

BACKGROUND: This study aimed to establish a simple prognostic scoring model based on tumor burden score (TBS) and PIVKA-II to predict long-term outcomes of α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients. METHODS: 511 patients were divided into the training cohort (n = 305) and the validation cohort (n = 206) at a ratio of 6:4. Receiver operating characteristic curves (ROC) were established to identify cutoff values of TBS and PIVKA-II. Kaplan-Meier curves were used to analyze survival outcomes. The multivariable Cox regression was used to identify variables independently associated with survival outcomes. The predictive performance of the TBS-PIVKA II score (TPS) model was compared with Barcelona clinic liver cancer (BCLC) stage and American Joint Committee on Cancer (AJCC TNM) stage. RESULTS: The present study established the TPS model using a simple scoring system (0, 1 for low/high TBS [cutoff value: 4.1]; 0, 1 for low/high PIVKA-II [cutoff value: 239 mAU/mL]). The TPS scoring model was divided into three levels according to the summation of TBS score and PIVKA-II score: TPS 0, TPS 1, and TPS 2. The TPS scoring model was able to stratify OS (training: p < 0.001, validation: p < 0.001) and early recurrence (training: p < 0.001; validation: p = 0.001) in the training cohort and the validation cohort. The TPS score was independently associated with OS (TPS 1 vs. 0, HR: 2.28, 95% CI: 1.01-5.17; TPS 2 vs. 0, HR: 4.21, 95% CI: 2.01-8.84) and early recurrence (TPS 1 vs. 0, HR: 3.50, 95% CI: 1.71-7.16; TPS 2 vs. 0, HR: 3.79, 95% CI: 1.86-7.75) in the training cohort. The TPS scoring model outperformed BCLC stage and AJCC TNM stage in predicting OS and early recurrence in the training cohort and the validation cohort. But the TPS scoring model was unable to stratify the late recurrence in the training cohort (p = 0.872) and the validation cohort (p = 0.458). CONCLUSIONS: The TPS model outperformed the BCLC stage and AJCC TNM stage in predicting OS and early recurrence of AFP-negative HCC patients after liver resection, which might better assist surgeons in screening AFP-negative HCC patients who may benefit from liver resection.

Nomogram to predict liver surgery-specific complications for hepatocellular carcinoma: A multicenter study.

BACKGROUND: Early identification of patients at risk for surgical complications enables surgeons to make better treatment decisions and optimize resource utilization. We propose to develop a nomogram for predicting the risk of moderate-to-severe liver surgery-specific complications after hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: We retrospectively enrolled HCC patients who underwent radical hepatectomy at four medical centers from January 2014 to January 2019 in southwestern China, randomly (7:3) divided into training and validation cohorts. We used least absolute shrinkage and selection operator (LASSO) logistic regression to build a nomogram model. RESULTS: The nomogram model contained 6 variables: diabetes mellitus (yes vs. no, OR: 2.32, 95% CI: 1.16-4.64, P = 0.02), major hepatectomy (yes vs. no, OR: 2.65, 95% CI: 1.64-4.27, P < 0.001), platelets (PLT, ≥100 × 103/µl vs. <100 × 103/µl, OR: 0.53, 95% CI: 0.33-0.87, P = 0.01), prothrombin time (PT, >13 s vs. ≤13 s, OR: 1.78, 95% CI: 1.04-3.05, P = 0.04), albumin-indocyanine green evaluation grade (ALICE grade, grade B vs. grade A, OR: 2.06, 95% CI: 1.17-3.61, P = 0.01), and prognostic nutrient index (PNI, >48 vs. ≤48, OR: 0.55, 95% CI: 0.33-0.92, P = 0.02). The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were 0.751 (95% CI, 0.703-0.799) and 0.743 (95% CI, 0.653-0.833) for the training and validation cohorts, respectively. Decision curve analysis (DCA) showed that the nomogram had good clinical value. CONCLUSION: We provide good preoperative predictors for the risk of moderate-to-high FABIB score complications in patients with HBV-related HCC posthepatectomy.

Prognosis after splenectomy plus pericardial devascularization vs transjugular intrahepatic portosystemic shunt for esophagogastric variceal bleeding.

BACKGROUND: Portal hypertension combined with esophagogastric variceal bleeding (EGVB) is a serious complication in patients with hepatitis B virus (HBV)-related cirrhosis in China. Splenectomy plus pericardial devascularization (SPD) and transjugular intrahepatic portosystemic shunt (TIPS) are effective treatments for EGVB. However, a comparison of the effectiveness and safety of those methods is lacking. AIM: To compare the prognosis after SPD vs TIPS for acute EGVB after failure of endoscopic therapy or secondary prophylaxis of variceal rebleeding (VRB) in patients with HBV-related cirrhosis combined with portal hypertension. METHODS: This retrospective cohort study included 318 patients with HBV-related cirrhosis and EGVB who underwent SPD or TIPS at West China Hospital of Sichuan University during 2009-2013. Propensity score-matched analysis (PSM), the Kaplan-Meier method, and multivariate Cox regression analysis were used to compare overall survival, VRB rate, liver function abnormality rate, and hepatocellular carcinoma (HCC) incidence between the two patient groups. RESULTS: The median age was 45.0 years (n = 318; 226 (71.1%) males). During a median follow-up duration of 43.0 mo, 18 (11.1%) and 33 (21.2%) patients died in the SPD and TIPS groups, respectively. After PSM, SPD was significantly associated with better overall survival (OS) (P = 0.01), lower rates of abnormal liver function (P < 0.001), and a lower incidence of HCC (P = 0.02) than TIPS. The VRB rate did not differ significantly between the two groups (P = 0.09). CONCLUSION: Compared with TIPS, SPD is associated with higher postoperative OS rates, lower rates of abnormal liver function and HCC, and better quality of survival as acute EGVB treatment after failed endoscopic therapy or as secondary prophylaxis of VRB in patients with HBV-related cirrhosis combined with portal hypertension. There is no significant between-group difference in VRB rates.

Insurance status impacts survival of hepatocellular carcinoma patients after liver resection.

BACKGROUND: This study intends to examine the effect of public insurance status on survival outcomes of HCC patients after liver resection in China. METHODS: We divided 2911 HCC patients after liver resection included in our study into the Urban Employed-based Medical Insurance group (UEBMI group, n = 1462) and the non-Urban Employed-based Medical Insurance group (non-UEBMI group, n = 1449). A propensity score matching (PSM) analysis was used to control confounding factors. Overall survival (OS) was estimated by Kaplan-Meier curves and Cox proportional hazard models based on variables screened by Lasso regression. Competing risk analysis was used to analyze cancer-specific survival (CSS). RESULTS: UEBMI group had more male patients (p = 0.031), patients in the UEBMI group were older (p < 0.001) and had lower Charlson Comorbidity Index scores (CCI score, p < 0.001). Meanwhile, patients in the UEBMI group had better liver function (albumin-bilirubin grade I [ALBI I], p < 0.001) and lower tumor burden (α-fetoprotein [AFP], p = 0.009; Barcelona Clinic Liver Cancer stage [BCLC], p = 0.026; Milan criteria, p < 0.001; tumor size, p < 0.001; microvascular invasion [MVI], p = 0.030; portal vein tumor thrombosis [PVTT], p = 0.002). More patients in the UEBMI group received laparoscopic surgery (p = 0.024) and adjuvant transarterial chemoembolization (TACE, p < 0.001). After PSM, patients in the two matched groups had similar characteristics. Patients with recurrent HCC in the UEBMI were more likely to receive curative therapy (p < 0.001) and less likely to receive supportive care (p < 0.001). HCC patients after liver resection in the non-UEBMI group had a worse OS before (p < 0.0001) and after PSM (p = 0.002). [Correction added on August 16, 2023 after first online publication. The p value has been updated in the preceding sentence.] In our Lasso-Cox risk regression model, public health insurance status was an independent factor linked with OS (non-UEBMI vs. UEBMI, hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.12-1.46; p < 0.001). In the competing risk analysis, patients in the UEBMI group had a lower cumulative incidence of CSS before (p < 0.001) and after PSM (p = 0.001), and public insurance status of HCC patients after liver resection remained independently associated with CSS (non-UEBMI vs. UEBMI; HR:1.36; 95% CI: 1.18-1.58; p < 0.001). CONCLUSIONS: Underinsured HCC patients after liver resection had worse survival outcomes. Less access to care for underinsured patients may explain the difference in survival, but the corresponding conclusions need to be further explored.

The application and prospection of augmented reality in hepato-pancreato-biliary surgery.

Augmented Reality (AR) is one of the main forms of Extended Reality (XR) application in surgery. hepato-pancreato-biliary (HPB) surgeons could benefit from AR as an efficient tool for making surgical plans, providing intraoperative navigation, and enhancing surgical skills. The introduction of AR to HPB surgery is less than 30 years but brings profound influence. From the early days of projecting liver models on patients' surfaces for locating a better puncture point to today's assisting surgeons to perform live donor liver transplantation, a series of successful clinical practices have proved that AR can play a constructive role in HPB surgery and has great potential. Thus far, AR has been shown to increase efficiency and safety in surgical resection, and, at the same time, can improve oncological outcomes and reduce surgical risk. Although AR has presented admitted advantages in surgery, AR's application is still immature as an emerging technique and needs more exploration. In this paper, we reviewed the principles of AR and its developing history in HPB surgery, describing its significant practical applications over the past 30 years. Reviewing the past attempts of AR in HPB surgery could make HPB surgeons a better understanding of future surgery and the digital trends in medicine. The routine uses of AR in HPB surgery, as an indication of the operating room entering the new era, is coming soon.

TIDE: adjuvant tislelizumab plus donafenib combined with transarterial chemoembolization for high-risk hepatocellular carcinoma after surgery: protocol for a prospective, single-arm, phase II trial.

Background: The high recurrence rate of hepatocellular carcinoma (HCC) after surgery negatively affects the prognosis of patients. There is currently no widely accepted adjuvant therapy strategy for patients with HCC. A clinical study of effective adjuvant therapy is still needed. Methods: In this prospective, single-arm, phase II clinical trial, an adjuvant regimen of donafenib plus tislelizumab combined with transarterial chemoembolization (TACE) will be used to treat enrolled HCC patients after surgery. Briefly, patients newly diagnosed with HCC by pathological examination who underwent curative resection and had a single tumor more than 5 cm in diameter with microvascular invasion as detected by pathological examination are eligible. The primary endpoint of the study is the recurrence-free survival (RFS) rate at 3 years, and secondary endpoints are the overall survival (OS) rate and the incidence of adverse events (AEs). The planned sample size, 32 patients, was calculated to permit the accumulation of sufficient RFS events in 3 years to achieve 90% power for the RFS primary endpoint. Discussion: Vascular endothelial growth factor (VEGF) and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathways regulate the relevant immunosuppressive mechanisms of HCC recurrence. Our trial will evaluate the clinical benefit of adding donafenib plus tislelizumab to TACE in patients with early-stage HCC and a high risk of recurrence. Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2200063003.

Tenofovir vs. entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma beyond Milan criteria after hepatectomy.

BACKGROUND: Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria. METHODS: Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence. RESULTS: The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS. CONCLUSIONS: Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.

Comparison of nucleoside and nucleotide analogs in the recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection: A multicenter study.

BACKGROUND: Antiviral therapy should reduce the recurrence of hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) after surgical resection. However, there is little research on whether various antiviral drugs have different prognostic effects in patients with HBV-related HCC after curative liver resection. The present study compared the effects of nucleotide analog (NtA) and nucleoside analog (NsA) antiviral therapies after surgical resection on the prognosis of HBV-related HCC. METHODS: A total of 1303 patients with HBV-related HCC who received curative hepatectomy at five institutes between April 2014 and April 2019 were retrospectively enrolled and analyzed. Propensity matching analysis was used to compare the outcomes of HCC patients given NsA versus NtA therapy. Subgroup analysis of patients treated with entecavir (ETV) and tenofovir disoproxil fumarate (TDF) was also performed. RESULTS: Among 1303 patients, 759 (58.2%) patients developed recurrence, and 460 (35.3%) patients died. Multivariable analyses revealed that NtA therapy significantly decreased the risk of HCC recurrence (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.51-0.80; p < 0.001) and HCC-related death (HR, 0.52; 95% CI, 0.36-0.76; p = 0.001) compared to that with NsA therapy. Subgroup analysis showed that TDF treatment was associated with significantly lower rates of HCC recurrence (HR, 0.64; 95% CI, 0.49-0.83; p = 0.001) and death (HR, 0.32; 95% CI, 0.20-0.50; p < 0.001) than ETV treatment. CONCLUSIONS: Nucleotide analog treatment, but not NsA treatment, significantly reduced the risk of HCC recurrence in patients with HBV-related HCC and improved overall survival after curative hepatic resection.

A three-dimensional study of the atlantodental interval in a normal Chinese population using reformatted computed tomography.

The atlantodental interval has been usually used for the evaluation of atlantoaxial instability. However, the asymmetry of the lateral atlantodental interval is occasionally found in healthy individuals. Controversy therefore exists as to the clinical significance of this asymmetry in patients after trauma. The purpose of this study was to determine the normal range of atlantodental intervals in normal individuals using reformatted computed tomography. In this study, C1-C2 vertebrae were imaged in 230 adult patients by a Lightspeed Vct CT (General Electric, CT, USA) with a slice thickness of 0.625 mm. After reformatting the original images, the anterior atlantodental interval (AADI) and lateral atlantodental interval (LADI) were measured. The AADI was found to be 1.83 ± 0.46 mm (0.9-3.4 mm) in males and 1.63 ± 0.43 mm (0.5-3.2 mm) in females. The AADI was significantly greater in males than in females (p < 0.05). The 95% confidence interval for AADI was 1.75-1.90 mm in males and 1.54-1.72 mm in females. No statistically significant differences were found between males and females in the left and right LADI, and LADI asymmetry. The left LADI was found to be 3.38 ± 0.87 mm (1.7-6.0 mm), and the right LADI was 3.42 ± 0.84 mm (1.7-5.9 mm) in males, while the left LADI was 3.30 ± 0.73 mm (1.5-5.3 mm) and the right LADI was 3.37 ± 0.92 mm (1.7-5.9 mm) in females. The 95% confidence interval for left LADI was 3.23-3.52 and 2.94-3.25 mm, and for right LADI was 3.27-3.56 and 3.18-3.56 mm in males and females, respectively. The mean asymmetry of LADI was 0.76 ± 0.66 mm (0.0-3.5 mm) in males and 0.73 ± 0.70 mm (0.0-3.7 mm) in females. The 95% confidence interval for LADI asymmetry was 0.65-0.87 mm in males and 0.59-0.88 mm in females. Most of the population was found to have an asymmetry ranging between 0.1 and 2.0 mm. The current study shows that LADI asymmetry is common in patients without any cervical spine abnormalities. LADI asymmetry may be a normal anatomic variant and there is no evidence to confirm that LADI asymmetry is a sensitive or specific indicator of traumatic atlantoaxial instability. Radiologists and clinicians should be aware of this normal range of asymmetry when interpreting CT scans of the atlantoaxial region.

Thoracic pedicle morphometry in different body height population: a three-dimensional study using reformatted computed tomography.

STUDY DESIGN: A three-dimensional study of the thoracic pedicle (T1-T12) morphometry in Chinese patients with different body height, using reformatted computed tomography (CT). OBJECTIVE: To quantify the dimensions of the thoracic pedicles and to analyze the relationship between body height and thoracic pedicle parameters. SUMMARY OF BACKGROUND DATA: The thoracic pedicle morphometry has been studied extensively in different populations using various techniques. Previous studies have shown a significantly smaller size of the thoracic pedicles in women than in men and in Asians than in Caucasians. Some authors postulated that it is the body height that contributes to the variation in the pedicle size. To our knowledge, however, no study has specifically analyzed the relationship between body height and thoracic pedicle parameters in detail. METHODS: In this study, T1 to T12 vertebrae were imaged in 126 Chinese patients by a Lightspeed Vct CT (General Electric, Bridgeport, Connecticut, USA). After reformatting the original images, the following parameters were calculated: outer pedicle width, outer pedicle height and pedicle cortical thickness of the pedicle isthmus, pedicle length, and transverse pedicle angle. All measured data were statistically analyzed by the independent t test and Pearson correlation test using SPSS software (SPSS Inc, Chicago, IL). RESULTS: The thoracic pedicle parameters were significantly smaller in women than in men except for the transverse pedicle angles and the pedicle cortical thickness. The percentage of outer pedicle widths less than 4.5 mm was extremely high at T3 to T9 in females and T4 to T7 in males. There was a much higher percentage of pedicle width of 4.5 mm or lesser, 4.0 mm or lesser, and 3.5 mm or lesser when body height was less than 160 cm. Body height is probably one of the main factors that contribute to the variation in pedicle size since a significant positive correlation was observed between pedicle size and body height. CONCLUSION: Body height is probably one of the main factors that contribute to the variation in pedicle size among different ethnic and sex groups. Transpedicular procedures using a 4.5-mm screw may not be applicable to much of the Chinese population at the upper and middle thoracic segments, especially for patients less than 160 cm in height. A reformatted CT evaluation is routinely recommended not only for choosing the proper screw but also for determining the feasibility of a true transpedicular procedure.

Reformatted computed tomographic evaluation of the thoracic pedicle in a Chinese population for the surgical application of transpedicular screw placement.

PURPOSE: To study the transverse thoracic pedicle diameter of a Chinese population and to determine the feasibility and safety of transpedicular screw fixation. METHODS: The authors studied the transverse pedicle diameter of the T1-T12 of the thoracic spine in a Chinese population using reformatted computed tomography. The data were compared with Caucasians and other Asians. RESULTS: The mean outer pedicle widths of the thoracic spine from T1 to T12 were 8.43, 6.65, 5.20, 4.44, 4.50, 4.87, 5.04, 5.32, 5.66, 6.65, 8.08 and 8.27 mm in males and 7.91, 6.03, 4.55, 3.91, 4.05, 4.31, 4.39, 4.60, 5.13, 5.67, 7.21 and 7.50 mm in females, respectively. Female patients have smaller dimensions compared with male patients. A significant percentage of patients have an outer pedicle width of less than 4.5 mm from T3 to T8, which is not suitable for transpedicular screw fixation with a 3.5 mm screw. CONCLUSIONS: The results of this study suggest that transpedicular screw fixation may not be suitable for the mid-thoracic regions in most Chinese females and that modified pedicle screw techniques or modified type of fixation is required in these patients. CT evaluation is a must before this procedure is performed.

SSFSE sequence functional MRI of the human cervical spinal cord with complex finger tapping.

PURPOSE: Functional MR imaging of the human cervical spinal cord was carried out on volunteers during alternated rest and a complex finger tapping task, in order to detect image intensity changes arising from neuronal activity. METHODS: Functional MR imaging data using single-shot fast spin-echo sequence (SSFSE) with echo time 42.4 ms on a 1.5 T GE Clinical System were acquired in eight subjects performing a complex finger tapping task. Cervical spinal cord activation was measured both in the sagittal and transverse imaging planes. Postprocessing was performed by AFNI (Analysis of Functional Neuroimages) software system. RESULTS: Intensity changes (5.5-7.6%) were correlated with the time course of stimulation and were consistently detected in both sagittal and transverse imaging planes of the cervical spinal cord. The activated regions localized to the ipsilateral side of the spinal cord in agreement with the neural anatomy. CONCLUSION: Functional MR imaging signals can be reliably detected with finger tapping activity in the human cervical spinal cord using a SSFSE sequence with 42.4 ms echo time. The anatomic location of neural activity correlates with the muscles used in the finger tapping task.

Characterization of vacuolar-ATPase and selective inhibition of vacuolar-H(+)-ATPase in osteoclasts.

V-ATPase plays important roles in controlling the extra- and intra-cellular pH in eukaryotic cell, which is most crucial for cellular processes. V-ATPases are composed of a peripheral V(1) domain responsible for ATP hydrolysis and integral V(0) domain responsible for proton translocation. Osteoclasts are multinucleated cells responsible for bone resorption and relate to many common lytic bone disorders such as osteoporosis, bone aseptic loosening, and tumor-induced bone loss. This review summarizes the structure and function of V-ATPase and its subunit, the role of V-ATPase subunits in osteoclast function, V-ATPase inhibitors for osteoclast function, and highlights the importance of V-ATPase as a potential prime target for anti-resorptive agents.

Osteoclast and its roles in calcium metabolism and bone development and remodeling.

Osteoclasts are multinucleated cells responsible for bone resorption and play important roles in normal skeletal development, in the maintenance of its integrity throughout life, and in calcium metabolism. During bone resorption, the cytoskeleton of osteoclasts undergoes extensive reorganization, with polarization and formation of ruffled borders to secrete acid and formation of sealing zone to prevent leakage. The differentiation and function of osteoclasts are in turn regulated by osteoblasts, stromal cells, and bone. They are also subjected to negative feedback regulation by extracellular and intracellular calcium concentrations.

Interleukin-1 beta induction of neuron apoptosis depends on p38 mitogen-activated protein kinase activity after spinal cord injury.

AIM: Interleukin-1 beta (IL-1beta) has been implicated as an extracellular signal in the initiation of apoptosis in neurons and oligodendrocytes after spinal cord injury (SCI). To further characterize the apoptotic cascade initiated by IL-1beta after SCI, we examined the expression of IL-1beta, p38 mitogen-activated protein kinase (p38 MAPK) and caspase-3 after SCI, and further investigated whether p38 MAPK was involved in neuron apoptosis induced by IL-1beta. METHODS: Adult rats were given contusion SCI at the T-10 vertebrae level with a weight-drop impactor (10 g weight dropped 25.0 mm). The expression levels of IL-1beta, p38 MAPK and caspase-3 after SCI were assessed with Western blots, immunohistochemistry staining, and real time reverse transcription polymerase chain reactions (RT-PCR). Neuron apoptosis was assessed with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method. RESULTS: Increased levels of IL-1beta and p38 MAPK were observed soon after injury, with a peak in expression levels within 6 h of injury. By 24 h after injury, caspase-3 expression was markedly increased in the injured spinal cord. TUNEL-positive cells were first observed in the lesioned area 6 h after SCI. The largest number of TUNEL-positive cells was observed at 24 h post-SCI. Intrathecal injection of the IL-1 receptor antagonist IL-1Ra significantly reduced expression of p38 MAPK and caspase-3, and reduced the number of TUNEL-positive cells. Moreover, intrathecal injection of an inhibitor of p38 MAPK, SB203580, also significantly reduced the expression of caspase-3, and reduced the number of TUNEL-positive cells in the injured spinal cord. CONCLUSION: The p38MAPK signaling pathway plays an important role in IL-1beta mediated induction of neuron apoptosis following SCI in rats.

Expression of c-fos in gastric myenteric plexus and spinal cord of rats with cervical spondylosis.

AIM: To determine the expression of c-fos in gastric myenteric plexus and spinal cord of rats with cervical spondylosis and its clinical significance. METHODS: A cervical spondylosis model was established in rats by destroying the stability of cervical posterior column, and the cord segments C(4-6) and gastric antrum were collected 3, 4 and 5 mo after the operation. Rats with sham operation were used as controls. c-fos neuronal counter-staining was performed with an immunohistochemistry method. Every third sections from C(4-6) segments were drawn. The 10 most labeled c-fos-immunoreactive (Fos-IR) neurons were counted, and the average number was used for statistical analysis. The mean of Fos-IR neurons in myenteric plexus was calculated after counting Fos-IR neurons in 25 ganglia from each antral preparation, and expressed as a mean count per myenteric ganglion. RESULTS: There were a few c-fos-positive neurons in the cervical cord and antrum in the control group. There was an increased c-fos expression in model group 3, 4 and 5 mo after operation, whereas there was no significant increase in c-fos expression in the control group at 3, 4 and 5 mo. More importantly, there was a significant difference in c-fos expression between rats followed up for 3 mo and those for 5 mo in the model group (11.20+/-2.26 vs 27.68+/-4.36, P<0.05, for the cervical cord; and 11.3+/-2.3 vs 29.3+/-4.6, P<0.05, for the gastric antrum). There was no significant difference between rats followed up for 3 mo and those for 4 mo and between rats followed up for 4 mo and those for 5 mo in the model group. CONCLUSION: c-fos expression in gastric myenteric plexus was dramatically associated with that in the spinal cord in rats with cervical spondylosis, suggesting that the gastrointestinal function may be affected by cervical spondylosis. If this hypothesis is confirmed by further studies, functional gastrointestinal diseases such as functional dyspepsia and irritable bowel syndrome could be explained by neurogastroenterology.