Ethics and governance of trustworthy medical artificial intelligence.

BACKGROUND: The growing application of artificial intelligence (AI) in healthcare has brought technological breakthroughs to traditional diagnosis and treatment, but it is accompanied by many risks and challenges. These adverse effects are also seen as ethical issues and affect trustworthiness in medical AI and need to be managed through identification, prognosis and monitoring. METHODS: We adopted a multidisciplinary approach and summarized five subjects that influence the trustworthiness of medical AI: data quality, algorithmic bias, opacity, safety and security, and responsibility attribution, and discussed these factors from the perspectives of technology, law, and healthcare stakeholders and institutions. The ethical framework of ethical values-ethical principles-ethical norms is used to propose corresponding ethical governance countermeasures for trustworthy medical AI from the ethical, legal, and regulatory aspects. RESULTS: Medical data are primarily unstructured, lacking uniform and standardized annotation, and data quality will directly affect the quality of medical AI algorithm models. Algorithmic bias can affect AI clinical predictions and exacerbate health disparities. The opacity of algorithms affects patients' and doctors' trust in medical AI, and algorithmic errors or security vulnerabilities can pose significant risks and harm to patients. The involvement of medical AI in clinical practices may threaten doctors 'and patients' autonomy and dignity. When accidents occur with medical AI, the responsibility attribution is not clear. All these factors affect people's trust in medical AI. CONCLUSIONS: In order to make medical AI trustworthy, at the ethical level, the ethical value orientation of promoting human health should first and foremost be considered as the top-level design. At the legal level, current medical AI does not have moral status and humans remain the duty bearers. At the regulatory level, strengthening data quality management, improving algorithm transparency and traceability to reduce algorithm bias, and regulating and reviewing the whole process of the AI industry to control risks are proposed. It is also necessary to encourage multiple parties to discuss and assess AI risks and social impacts, and to strengthen international cooperation and communication.

Critical values of monitoring indexes for perioperative major adverse cardiac events in elderly patients with biliary diseases.

BACKGROUND: Major adverse cardiac events (MACE) in elderly patients with biliary diseases are the main cause of perioperative accidental death, but no widely recognized quantitative monitoring index of perioperative cardiac function so far. AIM: To investigate the critical values of monitoring indexes for perioperative MACE in elderly patients with biliary diseases. METHODS: The clinical data of 208 elderly patients with biliary diseases in our hospital from May 2016 to April 2021 were retrospectively analysed. According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group. RESULTS: In the MACE compared with the non-MACE group, postoperative complications, mortality, hospital stay, high sensitivity troponin-I (Hs-TnI), creatine kinase isoenzyme (CK-MB), myoglobin (MYO), B-type natriuretic peptide (BNP), and D-dimer (D-D) levels were significantly increased (P < 0.05). Multivariate logistic regression showed that postoperative BNP and D-D were independent risk factors for perioperative MACE, and their cut-off values in the receiver operating characteristic (ROC) curve were 382.65 pg/mL and 0.965 mg/L, respectively. CONCLUSION: The postoperative BNP and D-D were independent risk factors for perioperative MACE, with the critical values of 382.65 pg/mL and 0.965 mg/L respectively. Consequently, timely monitoring and effective maintenance of perioperative cardiac function stability are of great clinical significance to further improve the perioperative safety of elderly patients with biliary diseases.

How to select the quantitative magnetic resonance technique for subjects with fatty liver: A systematic review.

BACKGROUND: Early quantitative assessment of liver fat content is essential for patients with fatty liver disease. Mounting evidence has shown that magnetic resonance (MR) technique has high accuracy in the quantitative analysis of fatty liver, and is suitable for monitoring the therapeutic effect on fatty liver. However, many packaging methods and postprocessing functions have puzzled radiologists in clinical applications. Therefore, selecting a quantitative MR imaging technique for patients with fatty liver disease remains challenging. AIM: To provide information for the proper selection of commonly used quantitative MR techniques to quantify fatty liver. METHODS: We completed a systematic literature review of quantitative MR techniques for detecting fatty liver, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Studies were retrieved from PubMed, Embase, and Cochrane Library databases, and their quality was assessed using the Quality Assessment of Diagnostic Studies criteria. The Reference Citation Analysis database (https:// www.referencecitationanalysis.com) was used to analyze citation of articles which were included in this review. RESULTS: Forty studies were included for spectroscopy, two-point Dixon imaging, and multiple-point Dixon imaging comparing liver biopsy to other imaging methods. The advantages and disadvantages of each of the three techniques and their clinical diagnostic performances were analyzed. CONCLUSION: The proton density fat fraction derived from multiple-point Dixon imaging is a noninvasive method for accurate quantitative measurement of hepatic fat content in the diagnosis and monitoring of fatty liver progression.

Lysine Interacts with Frizzled7 to Activate ß-Catenin in Satellite Cell-Participated Skeletal Muscle Growth.

This work provided an interesting finding of lysine (Lys) control on skeletal muscle growth besides protein synthesis. According to the isobaric tag for relative and absolute quantitation and molecular docking analyses, we found both in in vivo skeletal muscle and in vitro muscle satellite cells (MuSCs) that the frizzled7 (FZD7) expression level was positively correlated with Lys levels and this was consistent with the activation of the Wnt/ß-catenin pathway. On the other hand, FZD7 inhibition suppressed the Lys-rescued Wnt/ß-catenin pathway, FZD7 knockdown caused cell proliferation, and Wnt/ß-catenin pathway restrictions could not be compensated for by Lys or Wnt3a. Furthermore, the combination between Lys and recombinant pig frizzled7 (rpFZD7) protein was confirmed by isothermal titration calorimetry. This finding displayed concrete evidence that Lys is not only a molecular block of protein synthesis but is also a ligand for FZD7 to activate ß-catenin to stimulate MuSCs in promoting skeletal muscle growth.

A "4D" systemic view on meridian essence: Substantial, functional, chronological and cultural attributes.

The term Jingluo, translated as meridian or channel, is a core component of traditional Chinese medicine (TCM) and has played a fundamental role in guiding the clinical practice of acupuncture for thousands of years. However, the essence of the meridian remains elusive and is a source of both confusion and debate for researchers. In this study, a "4D" systemic view on the essence of the meridian, namely substantial, functional, chronological, and cultural dimensions, was proposed based on a review of the ancient medical classics, recent research developments, and results from clinical practice. Previous studies have primarily focused on the substantial dimension of the meridian system, with scant interpretation about its functional domain. Neither systemic data nor evaluations have been adequately documented. Additionally, a limited but increasing number of studies have focused on the chronological and cultural dimensions. More investigations that embody the holistic concept of TCM and integrate the systemic modes and advanced techniques with dominant diseases of TCM need to be performed to obtain a more comprehensive understanding of the essence of meridians. The goal of this study is to yield useful information in understanding the essence of meridians and provide a reference and perspective for further research.

The Challenges of Ethical Review in Clinical Research of Traditional Chinese Medicine.

The ethical review of TCM (traditional Chinese medicine) clinical research in China is highly consistent with that of Western medicine, but it lacks the characteristics and culture of TCM. Compared with modern medicine, TCM has its own characteristics, such as the theory of Yin-Yang and the five elements, the treatment of syndrome differentiation, and the compatibility of prescriptions. These characteristics determine the ethical particularity of TCM clinical research. This article discusses the challenges in the ethical review of TCM clinical research, such as scientific design, efficacy evaluation, risk assessment, informed consent, and placebo use. We propose opportunities and difficulties in the ethical review of TCM clinical research and provide some relevant suggestions.

Combination of preoperative fibrinogen and D-dimer as a prognostic indicator in pancreatic ductal adenocarcinoma patients undergoing R0 resection.

BACKGROUND: Patients with malignant tumors frequently exhibit hyperactivation of the coagulation system and secondary increased fibrinolytic activity. Fibrinogen and D-dimer are common indicators that are crucial in the coagulation/fibrinolysis system. Both indicators have been verified to have predictive value in the overall survival (OS) of many patients with solid malignancies. AIM: To explore the prognostic significance of fibrinogen combined with D-dimer in pancreatic ductal adenocarcinoma (PDAC) patients undergoing radical R0 resection. METHODS: We retrospectively analyzed the clinical data of 282 patients with PDAC undergoing radical R0 resection in the Cancer Hospital, Chinese Academy of Medical Sciences, between January 2010 and December 2019. The surv_cutpoint function of R language was used to determine the optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration. Enrolled patients were further divided into the any-high group (high preoperative fibrinogen concentration and/or high preoperative D-dimer concentration) and the low-low group (low preoperative fibrinogen and D-dimer concentrations) according to the optimal cutoff values. RESULTS: The optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration were 3.31 g/L and 0.53 mg/L, respectively. Furthermore, multivariate Cox regression analysis showed that the preoperative fibrinogen concentration (HR: 1.603, 95%CI: 1.201-2.140, P = 0.001) and preoperative D-dimer concentration (HR: 1.355, 95%CI: 1.019-1.801, P = 0.036) exhibited obvious correlations with the OS of PDAC patients undergoing radical R0 resection. A prognostic analysis was further performed based on the subgroup results by using fibrinogen combined with D-dimer. The median OS duration of the low-low group (31.17 mo) was significantly longer than that of the any-high group (15.43 mo). Additionally, multivariate Cox regression analysis revealed that the degree of differentiation (P < 0.001), lymph node metastasis (HR: 0.663, 95%CI: 0.497-0.883, P = 0.005), preoperative CA19-9 level (HR: 1.699, 95%CI: 1.258-2.293, P = 0.001), adjuvant therapy (HR: 1.582, 95%CI: 1.202-2.081, P = 0.001) and preoperative combined grouping (HR: 2.397, 95%CI: 1.723-3.335, P < 0.001) were independent predictors of OS in PDAC patients undergoing radical R0 resection. CONCLUSION: Preoperative fibrinogen combined with D-dimer plays a predictive role in OS, and low preoperative fibrinogen and D-dimer concentrations can indicate prolonged OS in PDAC patients undergoing radical R0 resection.

Therapeutic experience of an 89-year-old high-risk patient with incarcerated cholecystolithiasis: A case report and literature review.

BACKGROUND: The global pandemic of coronavirus disease 2019 pneumonia poses a particular challenge to the emergency surgical treatment of elderly patients with high-risk acute abdominal diseases. Elderly patients are a high-risk group for surgical treatment. If the incarceration of gallstones cannot be relieved, emergency surgery is unavoidable. CASE SUMMARY: We report an 89-year-old male patient with acute gangrenous cholecystitis and septic shock induced by incarcerated cholecystolithiasis. He had several coexisting, high-risk underlying diseases, had a history of radical gastrectomy for gastric cancer, and was taking aspirin before the operation. Nevertheless, he underwent emergency laparoscopic cholecystectomy, with maintenance of postoperative heart and lung function, successfully recovered, and was discharged on day 8 after the operation. CONCLUSION: Emergency surgery for elderly patients with acute abdominal disease is safe and feasible during the coronavirus disease 2019 pandemic, the key is to abide strictly by the hospital's epidemic prevention regulations, fully implement the epidemic prevention procedure for emergency surgery, fully prepare before the operation, accurately perform the operation, and carefully manage the patient postoperatively.

mTORC1-Mediated Satellite Cell Differentiation Is Required for Lysine-Induced Skeletal Muscle Growth.

Skeletal muscle is the primary source of protein for humans. However, the mechanisms of skeletal muscle growth, such as nutrition control, remain unknown. Moreover, the function of lysine (Lys) in controling skeletal muscle growth has gradually demonstrated that Lys is not only substantial for protein synthesis but also a signaling molecule for satellite cell (SC) activation. In the current work, the number of differentiated SCs in the longissimus thoracis muscle and the fusion index of SCs were both governed by Lys supplementation. Meanwhile, the myogenic regulatory factors and the mammalian target of rapamycin complex 1 (mTORC1) pathway showed the same tendencies of changes as the differentiation of SCs. After Lys was resupplemented with rapamycin, the mTORC1 pathway was inhibited and the differentiation ability of SCs was suppressed. Collectively, the results showed that the mTORC1-pathway-mediated SC differentiation was required for Lys-promoted skeletal muscle growth.

Lysine-induced swine satellite cell migration is mediated by the FAK pathway.

Lysine (Lys) is an essential amino acid for mammals in promoting protein synthesis and skeletal muscle growth. However, the underlying mechanism by which Lys governs muscle growth remains unknown. Lys is not only a material for protein synthesis but also a signaling molecule. Cell migration is a fundamental process for satellite cells (SCs) to promote muscle fiber hypertrophy and thus increase muscle mass. Nevertheless, the communication between Lys and SC has not yet attracted sufficient attention. In this study, we investigated whether Lys directly stimulates SC migration and whether this effect is mediated via the focal adhesion kinase (FAK) pathway. The results of a cell wound-healing assay and transwell assays indicated a significant inhibition of migration ability by Lys deficiency. In addition, the phosphorylation of FAK, paxillin and protein kinase B (Akt) was significantly suppressed, as were the level of integrin ß3. Fortunately, we found that increasing Lys levels from deficiency to sufficiency rescued the migration ability to the control level. Moreover, compared with those in the Lys-deficiency group, the proteins in the FAK pathways were reactivated in the Lys-resupplementation group. In conclusion, these findings indicate that the FAK pathway mediates Lys-induced SC migration.

Effects of pioglitazone hydrochloride and vitamin E on meat quality, antioxidant status and fatty acid profiles in finishing pigs.

To investigate the effects of pioglitazone hydrochloride (PGZ) and vitamin E (VE), 160 Duroc × Landrace × Large White pigs were randomly divided into a 2 × 2 factorial arrangement with 2 levels of PGZ (0 or 15 mg/kg) and 2 levels of VE (0 or 325 mg/kg) for 28 days. Each group had 5 replicates with 8 pigs, half males and half females. Feeding PGZ increased intramuscular fat and VE supplementation decreased cooking loss (P < 0.05). Feeding VE increased total polyunsaturated fatty acid (PUFA), C18:2n-6 and C18:3n-3 (P < 0.05). For 18:3n-3, the increase in C18:3n-3 due to VE was accentuated when combined with PGZ (P < 0.001). Additionally, VE tended to increase superoxide dismutase (P = 0.079) and glutathione peroxidase activity (P = 0.054). In summary, PGZ and VE had positive effects on pork quality by decreasing cooking loss and increasing intramuscular fat and antioxidant capacity, and may prove useful in improving the healthfulness of fatty acid profiles.

Dietary Supplementation with Pioglitazone Hydrochloride and Chromium Methionine Improves Growth Performance, Meat Quality, and Antioxidant Ability in Finishing Pigs.

This work was designed to investigate the synergistic effects of pioglitazone hydrochloride (PGZ) and chromium methionine (CrMet) on meat quality, muscle fatty acid profile, and antioxidant ability of pigs. Pigs in four groups were fed a basic diet or basic diet supplemented with 15 mg/kg of PGZ, 200 µg/kg of CrMet, or 15 mg/kg of PGZ + 200 µg/kg of CrMet. In comparison to the control group, the average daily feed intake, feed/gain ratio, and serum high-density lipoprotein level decreased in the PGZ + CrMet group. Dietary PGZ + CrMet supplementation increased carcass dressing percentage, intramuscular fat, and marbling score. The percentages of C18:1ω-9c, C18:2ω-6c, C18:3ω-3, and polyunsaturated fatty acid (PUFA) in the longissimus thoracis muscle were increased in the PGZ + CrMet group. Greater superoxide dismutase and glutathione peroxidase activities were observed in the PGZ + CrMet group compared to the control group. Collectively, these findings suggested that feed with PGZ and CrMet improved the growth performance and meat quality, especially for PUFA proportions and antioxidant ability.

Ischemic or toxic injury: A challenging diagnosis and treatment of drug-induced stenosis of the sigmoid colon.

A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of drug-induced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids.

Therapeutic experience of 289 elderly patients with biliary diseases.

AIM: To present clinical characteristics, diagnosis and treatment strategies in elderly patients with biliary diseases. METHODS: A total of 289 elderly patients with biliary diseases were enrolled in this study. The clinical data relating to these patients were collected in our hospital from June 2013 to May 2016. Patient age, disease type, coexisting diseases, laboratory examinations, surgical methods, postoperative complications and therapeutic outcomes were analyzed. RESULTS: The average age of the 289 patients with biliary diseases was 73.9 ± 8.5 years (range, 60-102 years). One hundred and thirty-one patients (45.3%) had one of 10 different biliary diseases, such as gallbladder stones, common bile duct stones, and cholangiocarcinoma. The remaining patients (54.7%) had two types of biliary diseases. One hundred and seventy-nine patients underwent 9 different surgical treatments, including pancreaticoduodenectomy, radical resection of hilar cholangiocarcinoma and laparoscopic cholecystectomy. Ten postoperative complications occurred with an incidence of 39.3% (68/173), and hypopotassemia showed the highest incidence (33.8%, 23/68). One hundred and sixteen patients underwent non-surgical treatments, including anti-infection, symptomatic and supportive treatments. The cure rate was 97.1% (168/173) in the surgical group and 87.1% (101/116) in the non-surgical group. The difference between these two groups was statistically significant (χ2 = 17.227, P < 0.05). CONCLUSION: Active treatment of coexisting diseases, management of indications and surgical opportunities, appropriate selection of surgical procedures, improvements in perioperative therapy, and timely management of postoperative complications are key factors in enhancing therapeutic efficacy in elderly patients with biliary diseases.

The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus.

PURPOSE: To further improve the effectiveness and prognosis of primary hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), the current status of treatment for HCC with PVTT was reviewed. METHODS: A Medline search was undertaken to identify articles using the keywords "HCC", "PVTT" and "therapy". Additional papers were identified by a manual search of the references from the key articles. RESULTS: PVTT, as a common complication of HCC, was divided into type I ∼ IV. The therapeutic approach is mainly composed of five types: surgical resection, regional interventional therapy, radiotherapy, combination therapy, targeted therapy. All of these therapeutic approaches were separately evaluated in detail. CONCLUSIONS: For those resectable tumors, the better choice for treatment of HCC with PVTT should be hepatectomy and removal of PVTT. For those unresectable tumors, TACE (especially the super-selective TACE) has been the preferred palliative treatment, the other regional interventional therapy and/or radiotherapy could improve the therapeutic effects. The multidisciplinary treatments may further improve the quality of life and prolong the survival period for the HCC patients associated with PVTT.

Preparation of magnetic resonance probes using one-pot method for detection of hepatocellular carcinoma.

AIM: To prepare the specific magnetic resonance (MR) probes for detection of hepatocellular carcinoma (HCC) using one-pot method. METHODS: The carboxylated dextran-coated nanoparticles were conjugated with anti-α-fetoprotein (anti-AFP) or anti-glypican 3 (anti-GPC3) antibodies through 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS)-mediated reaction to synthesize the probes. The physical and chemical properties of the probes were determined by transmission electron microscopy (TEM) and dynamic light scattering, and the relaxivity was compared to uncombined ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) using a 1.5T clinical MR scanner. The binding efficiency of the antibodies to nanoparticles was measured with an ultraviolet-visible spectrophotometer. In addition, the probes were incubated with targetable cells in vitro. RESULTS: The superparamagnetic MR probes (anti-GPC3-USPION probe and anti-AFP-USPION probe) were synthesized using one-pot method. Their mean hydrodynamic diameter was 47 nm with a broader slight size distribution. The coupling efficiency of carboxylated dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) with anti-GPC3 or anti-AFP antibody was 15.9% and 88.8%, respectively. Each of the USPIO nanoparticles may bind 3 GPC3 antibodies or 12 AFP antibodies. The statistical analysis showed no significance (P > 0.05) in shortening the T1 and T2 values when comparing the USPIO-AFP or USPIO-GPC3 to USPIO. Analysis of TEM images revealed that anti-GPC3-USPION probes and anti-AFP-USPION probes could specifically enter into the HepG2 cell by combining with the GPC3 receptors or AFP receptors, whereas the HepG2 cell sample incubated with USPIONs showed no or few nanoparticles in the cytoplasm. CONCLUSION: The synthesized probes using one-pot method can be used for in vitro experimental study and have potential clinical application in MR imaging for detection of hepatocellular carcinomas.

Superparamagnetic iron oxide-enhanced magnetic resonance imaging for focal hepatic lesions: systematic review and meta-analysis.

AIM: To evaluate the performance of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) in the detection and characterization of focal hepatic lesions (FHLs). METHODS: This meta-analysis compared relevant studies that were identified by searching PubMed, EMBASE, and the Cochrane Library databases for articles published between January 1988 and September 2014 and that met the following criteria: (1) SPIO-enhanced MRI was conducted to identify FHLs and data were sufficient for pooled analysis using Meta-DiSc 1.4; (2) hepatocellular carcinomas (HCCs) were differentiated from other FHLs; (3) well-differentiated HCCs (WD-HCCs) were contradistinguished from dysplastic nodules; and (4) WD-HCCs were compared with moderately and poorly differentiated HCCs (MD- and PD-HCCs, respectively). RESULTS: The data obtained from 15 eligible studies yielded a sensitivity of 85% and a specificity of 78% for differentiating between HCCs and other FHLs. The sensitivity was unchanged and the specificity was increased to 87% when non-HCC malignancies were excluded. Comparative analyses between WD-HCCs and MD- and PD-HCCs from seven studies showed a sensitivity of 98% and a specificity of 50% for the diagnosis of MD- and PD-HCCs, and the area under the summary receiver operating characteristics (sROC) curve was 0.97. A comparison between WD-HCCs and dysplastic nodules revealed a sensitivity of 50% and a specificity of 92% for the diagnosis of WD-HCCs and the area under the sROC curve was 0.80. CONCLUSION: SPIO-enhanced MRI is useful in differentiating between HCCs and other FHLs.

Abnormal mitochondrial function impairs calcium influx in diabetic mouse pancreatic beta cells.

BACKGROUND: Abnormal insulin secretion of pancreatic beta cells is now regarded as the more primary defect than the insulin function in the etiology of type 2 diabetes. Previous studies found impaired mitochondrial function and impaired Ca(2+) influx in beta cells in diabetic patients and animal models, suggesting a role for these processes in proper insulin secretion. The aim of this study was to investigate the detailed relationship of mitochondrial function, Ca(2+) influx, and defective insulin secretion. METHODS: We investigated mitochondrial function and morphology in pancreatic beta cell of diabetic KK-Ay mice and C57BL/6J mice. Two types of Ca(2+) channel activities, L-type and store-operated Ca(2+) (SOC), were evaluated using whole-cell patch-clamp recording. The glucose induced Ca(2+) influx was measured by a non-invasive micro-test technique (NMT). RESULTS: Mitochondria in KK-Ay mice pancreatic beta cells were swollen with disordered cristae, and mitochondrial function decreased compared with C57BL/6J mice. Ca(2+) channel activity was increased and glucose induced Ca(2+) influx was impaired, but could be recovered by genipin. CONCLUSION: Defective mitochondrial function in diabetic mice pancreatic beta cells is a key cause of abnormal insulin secretion by altering Ca(2+) influx, but not via Ca(2+) channel activity.

Effects and mechanisms of store-operated calcium channel blockade on hepatic ischemia-reperfusion injury in rats.

AIM: To further investigate the important role of store-operated calcium channels (SOCs) in rat hepatocytes and to explore the effects of SOC blockers on hepatic ischemia-reperfusion injury (HIRI). METHODS: Using freshly isolated hepatocytes from a rat model of HIRI (and controls), we measured cytosolic free Ca(2+) concentration (by calcium imaging), net Ca(2+) fluxes (by a non-invasive micro-test technique), the SOC current (I(SOC); by whole-cell patch-clamp recording), and taurocholate secretion [by high-performance liquid chromatography and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays]. RESULTS: Ca(2+) oscillations and net Ca(2+) fluxes mediated by Ca(2+) entry via SOCs were observed in rat hepatocytes. I(SOC) was significantly higher in HIRI groups than in controls (57.0 ± 7.5 pA vs 31.6 ± 2.7 pA, P < 0.05) and was inhibited by La(3+). Taurocholate secretion by hepatocytes into culture supernatant was distinctly lower in HIRI hepatocytes than in controls, an effect reversed by SOC blockers. CONCLUSION: SOCs are pivotal in HIRI. SOC blockers protected against HIRI and assisted the recovery of secretory function in hepatocytes. Thus, they are likely to become a novel class of effective drugs for prevention or therapy of HIRI patients in the future.