Effects of Ca^(2+) channel blockers on store-operated Ca^(2+) channel currents of Kupffer cells after hepatic ischemia/reperfusion injury in rats

AIM： To study the effects of hepatic ischemia/ reperfusion （I/R） injury on store-operated calcium channel （SOC） currents （Isoc） in freshly isolated rat Kupffer cells, and the effects of Ca^2＋ channel blockers, 2-aminoethoxydiphenyl borate （2-APB）, SK＆F96365, econazole and miconazole, on Isoc in isolated rat Kupffer cells after hepatic I/R injury.METHODS： The model of rat hepatic I/R injury was established. Whole-cell patch-clamp techniques were performed to investigate the effects of 2-APB, SK＆F96365, econazole and miconazole on Isoc in isolated rat Kupffer cells after hepatic I/R injury.RESULTS： I/R injury significantly increased Isoc from -80.4±25.2pA to -159.5±34.5pA （^bp 〈 0.01, n = 30）. 2-APB （20, 40, 60, 80, 100 pmol/L）, SK＆F96365 （5, 10, 20, 40, 50 pmol/L）, econazole （0.1, 0.3, 1, 3, 10 μmol/L） and miconazole （0.1, 0.3, 1, 3, 10 μmol/L） inhibited Isoc in a concentration-dependent manner with IC50 of 37.41 μmol/L （n = 8）, 5.89 μmol/L （n = 11）, 0.21 μmol/L （n = 13）, and 0.28 μmol/L （n = 10）. The peak value of Isoc in the I-V relationship was decreased by the blockers in different concentrations, but the reverse potential of Isoc was not transformed. CONCLUSION： SOC is the main channel for the influx of Ca^2＋ during hepatic I/R injuries. Calcium channel blockers, 2-APB, SK＆F96365, econazole and miconazole,have obviously protective effects on I/R injury, probably by inhibiting Isoc in Kupffer cells and preventing the activation of Kupffer cells.

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 ultravioletvisible spectrophotometer.In addition, the probes were incubated with targetable cells in vitro.RESULTS: The superparamagnetic MR probes(antiGPC3-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 USPIOGPC3 to USPIO.Analysis of TEM images revealed that anti-GPC3-USPION probes and anti-AFP-USPION probes could specifically enter into the Hep G2 cell by combining with the GPC3 receptors or AFP receptors, whereas the Hep G2 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 superpara-magnetic 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 Pub Med, 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-DiS c 1.4;(2) hepatocellular carcinomas(HCCs) were differentiated from other FHLs;(3) well-differentiated HCCs(WDHCCs) were contradistinguished from dysplastic nodules; and(4) WD-HCCs were compared with moderately and poorly differentiated HCCs(MD- and PDHCCs, 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(sR OC) 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 sR OC curve was 0.80.CONCLUSION: SPIO-enhanced MRI is useful in differentiating between HCCs and other FHLs.

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 (chi(2) = 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.

Measuring Ca^(2+) influxes of TRPC1-dependent Ca^(2+) channels in HL-7702 cells with Non-invasive Micro-test Technique

AIM： To explore the possibility of using the Noninvasive Micro-test Technique （NMT） to investigate the role of Transient Receptor Potential Canonical 1 （TRPC1） in regulating Ca^2＋ influxes in HL-7702 cells, a normal human liver cell line.METHODS： Net Ca^2＋ fluxes were measured with NMT, a technology that can obtain dynamic information of specific/selective ionic/molecular activities on material surfaces, non-invasively. The expression levels of TRPCl were increased by liposomal transfection, whose effectiveness was evaluated by Western-blotting and single cell reverse transcription-polymerase chain reaction.RESULTS： Ca^2＋ influxes could be elicited by adding 1 mmol/L CaCl2 to the test solution of HL-7702 cells. They were enhanced by addition of 20 μmol/L noradrenalin and inhibited by 100 μmol/L LaCl3 （a non-selective Ca^2＋ channel blocker）; 5 μmol/L nifedipine did not induce any change. Overexpression of TRPCl caused increased Ca^2＋ influx. Five micromoles per liter nifedipine did not inhibit this elevation, whereas 100 μmol/L LaCI3 did.CONCLUSION： In HL-7702 cells, there is a type of TRPCl-dependent Ca^2＋ channel, which could be detected v/a NMT and inhibited by La^3＋.

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.

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 druginduced 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 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.

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 Ddimer(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.

Current Status of Surgical Treatment of Biliary Diseases in Elderly Patients in China

To the Editor： According to the Chinese National Bureau of Statistics in October 1999, the population aged ≥60 years reached 10% of the total population, indicating that China was entering into an aging society, By the end of 2017, the population aged ≥60 years was 240,900,000, accounting for 17.3% of the total population. With the rapidly aging population, binary diseases in elderly patients have become frequent in China, with a morbidity rate of 8-11%. Due to lowered stress response, defense ability, and immunity, biliary diseases in elderly patients are characterized by an increase in coexisting diseases, rapid progression, poor surgical tolerance, high surgical risk, frequent postoperative complications, and high mortality. Thus, it is important to explore effective treatment methods in elderly patients with biliary diseases. Based on our clinical experience in the treatment of elderly patients with biliary diseases,[1] along with previous studies, this report presented the current status of surgical treatment of elderly patients with biliary diseases in China.[2]

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“4 D”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.