Objective To explore the causal relationship between rheumatoid arthritis(RA)and iron deficiency a-nemia(IDA)in European population by two-sample Mendelian randomization analysis.Methods The single nu-cleotide polymorphisms(SNPs)of RA and IDA were analyzed using public genome-wide association studies(GWAS).The inverse variance weighting method(IVW)was used as the main analysis method to evaluate the causal effect of RA on IDA.MR-Egger method,weighted median method(WM),weighted model method and simple model method were used as regression supplements to evaluate the robustness of sensitivity analysis results.The het-erogeneity function was used to calculate the P-value to test the heterogeneity,and the intercept term intercept was used to test the level pleiotropy.Results In the FINNGEN database at the genome-wide level,strong-related SNPs that removed linkage disequilibrium and met the P＜5.0 × 10-8 by Mendelian randomization analysis were select-ed.After integrating exposure and outcome data,31 SNPs were obtained as the final effective instrumental variables.IVW showed that RA was a risk factor for IDA(the risk of IDA in RA patients was 1.064 times higher than that in non-RA patients,OR=1.064,95％CI:1.028-1.103).The weighted median method and MR-Egger method re-sults supported the positive correlation between RA and IDA.The intercept value was close to 0,indicating that there was no horizontal pleiotropy between exposure and outcome.The heterogeneity function's P＜0.05 indicated that there was heterogeneity between exposure and outcome,but the random effect model test showed P＜0.05,indi-cating that even if there was heterogeneity in causality,the overall trend was stable.Conclusion RA is a risk factor for IDA,and there is a positive correlation between RA and IDA.

Objective To investigate the causal relationship between rheumatoid arthritis (RA) and pulmonary hypertension (PH) by the Mendelian randomization design method.Methods The data on single nucleotide polymorphisms (SNPs) of exposure and outcome were obtained by using publicly available ge-nome-wide association studies and the summary analysis was conducted;the inverse variance-weighted (IVW) method as the primary analysis method was used to assess the causal effect of exposure factors (RA) on the outcomes (PH);the MR-Egger regression method,weighted median method (WM),weighted model and sim-ple model were used as supplementary regression explanations to conduct the sensitivity analysis for evalua-ting the robustness of results;the "heterogeneity" function was used to calculate the "P value" for testing the heterogeneity,and the "horizontal pleiotropy" function was used to calculate the "P value" to test the level pleiotropy.Results In the "FINNGEN data" included in the GWAS database,the SNPs had the strong corre-lation after removing the linkage imbalance by Mendelian random analysis and satisfying "P<5×10-8" were selected,the effective instrumental variables were obtained by integrating the exposure and outcome.The IVW results showed that RA was a risk factor for PH (OR=1.295,95％CI:1.053-1.593,P=0.014)."heteroge-neity" function test showed that the results had no heterogeneity (P=0.221);" horizontal pleiotropy" func-tion test showed that the results had no horizontal pleiotropy (P=0.877),and the total results were steady and reliable.Conclusion RA is a risk factor for PH,and RA is positively associated with PH.

Objective To investigate the accuracy of liver stiffness (LS) as a noninvasive index in predicting hepatic venous pressure gradient (HVPG) in patients with decompensated liver cirrhosis and the value of LS in the diagnosis of decompensated liver cirrhosis. Methods A retrospective analysis was performed for the clinical data of 88 patients with decompensated cirrhosis due to viral hepatitis or decompensated alcoholic cirrhosis who received both HVPG measurement and LS measurement by acoustic radiation force impulse (ARFI) in Department of Gastroenterology, Nanjing Drum Tower Hospital, from April 2013 to June 2021, and according to HVPG, the patients were divided into serious portal hypertension (SPH) (HVPG≥20 mmHg) group with 24 patients and non-SPH (HVPG < 20 mmHg) group with 64 patients. The two groups were compared in terms of LS, spleen stiffness, portal vein velocity, and related biochemical parameters. The t -test or the Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. A Pearson correlation analysis was used to investigate the correlation of different noninvasive indices with HVPG, and a Logistic regression analysis was used to investigate the association of different noninvasive indices with the risk of SPH. Receiver operating characteristic (ROC) curves were plotted for different noninvasive indices in predicting HVPG≥20 mmHg, and the area under the ROC curve (AUC), sensitivity, specificity, maximum Youden index, and corresponding cut-off value were calculated to investigate the value of each index in predicting SPH. Results Among the 88 patients, 76 had decompensated cirrhosis due to viral hepatitis and 12 had decompensated alcoholic cirrhosis. There were no significant differences between the SPH group and the non-SPH group in age, sex, white blood cell count, hemoglobin, platelet count, prothrombin time, alanine aminotransferase, aspartate aminotransferase, albumin, serum sodium, creatinine, Child-Pugh class, and spleen stiffness, while there was a significant difference in LS between the two groups ( t =-3.970, P < 0.01). The correlation analysis showed that HVPG was positively correlated with LS ( r =0.458, P < 0.001). The Logistic regression analysis showed that LS was a risk factor for SPH (odds ratio=3.941, 95% confidence interval: 1.245-12.476, P =0.020). The ROC curve analysis showed that LS had an AUC of 0.751 in predicting the onset of SPH, with a sensitivity of 54.17% and a specificity of 90.63% at the optimal cut-off value of 2.295 m/s. Conclusion In patients with decompensated cirrhosis, LS measured by ARFI is correlated with HVPG and has a certain value in the non-invasive diagnosis of decompensated cirrhosis with HVPG≥20 mmHg.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To explore the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of esophago-gastric variceal bleeding (EGVB) complicated with cavernous transformation of portal vein (CTPV).Methods:From January 1, 2015 to December 31, 2018, the clinical data of liver cirrhosis patients with EGVB and complicated with (CTPV group) or without (non-CTPV group) CTPV receiving TIPS at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School were retrospectively analyzed. The success rate of operation, stent patency rate, recurrent bleeding rate, incidence and survival rate of hepatic encephalopathy of CTPV group and non-CTPV group were analyzed. Independent samples t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Kaplan-Meier method was used for survival analysis. Results:A total of 37 liver cirrhosis patients with EGVB and CTPV receiving TIPS treatment were screened out, among which 10 patients (27.0%) failed the portal vein puncture during the TIPS and switched to endoscopic treatment, the success rate was 73.0%. A total of 460 liver cirrhosis patients with EGVB and non-CTPV received TIPS treatment, among which TIPS in 18 patients (3.9%) was failed, and the success rate was 96.1%. With 1∶2 ratio propensity matching, 54 patients were enrolled in non-CTPV group. In the CTPV group, after TIPS treatment, the average portal vein pressure decreased from (28.9±5.1) mmHg (1 mmHg=0.133 kPa) to (18.8±4.5) mmHg, and the difference was statistically significant ( t=7.122, P<0.01). The median follow-up time was 33 months(1 to 66 months). There were no significant differences between the CTPV group and the non-CTPV group in one-year of cumulative stent patency rate (75.0% vs. 86.8%), recurrent upper gastrointestinal bleeding rate of hepatic encephalopathy (21.0% vs. 10.0%), the incidence of hepatic encephalopathy (34.8% vs. 22.2%) and the survival rate (80.7% vs. 88.9%)(all P >0.05). Conclusion:TIPS is safe and effective in the treatment of liver cirrhosis patients with EGVB and CTPV, and does not increase the incidence of postoperative complications and long-term mortality.

Simulation-based medical education can ensure medical safety, reduce medical errors and improve students' clinical skills. At present, the main problems in medical teaching are the conflict between doctors and patients, the contradiction between medical teaching and ethics, the shortage of teaching resources and the lack of a universal assessment standard. The advantages of simulation-based medical education are its safety, repeatability, standardization, controllability, relative authenticity, and the cultivation of humanistic spirit and teamwork for students. Simulation-based medical education has two major limits. First, its teaching effect relies on the function and quality of each model. Second, simulation cannot replace clinical practice. This article proposes the following ways and means for promoting the simulation-based medical education: training of faculty is the core, establishment of courses is the focus, cooperation and communication is an important way to promote development, and phased and refined development is the future direction.

OBJECTIVEBased on the western medication, to evaluate the advantages in the morning blood pressure treated with acupuncture at Fengchi (GB 20) and Neck-Jiaji (EX-B 2) combined with acupuncture technique for activating blood circulation, eliminating wind and regulating the liver and spleen in the patients with essential hypertension.

METHODSA total of 90 patients of essential hypertension of the mild and moderate degrees were randomized into a medication group (30 cases, 3 dropping), No.1 acupuncture group (30 cases, 2 dropping) and No.2 acupuncture group (30 cases, 1 dropping). In the medication group, adalat was prescribed for oral administration, 30 mg at 7 am every day, continuously for 6 weeks. In the No.1 acupuncture group, on the basis of the treatment as the medication group, the acupuncture technique for activating blood circulation, eliminating wind and regulating the liver and spleen was applied and the acupoints were Renying (ST 9), Hegu (LI 4), Taichong (LR 3), Quchi (LI 11) and Zusanli (ST 36). In the No.2 acupuncture group, on the basis of the treatment as the No.1 acupuncture group, Fengchi (GB 20) and Neck-Jiaji (EX-B 2) were added in acupuncture. Acupuncture was given in the time zone from 8 am through 10 am every day, once a day, 5 times a week, totally for 6 weeks. Separately, before treatment and in 2, 4 and 6 weeks of treatment, the morning blood pressure, the control rate and the symptom score were observed in the patients of the three groups. The morning blood pressure was followed up in 3 and 6 months separately.

RESULTSCompared with those before treatment, in 2, 4 and 6 weeks of treatment, the levels of blood pressure reduced in the patients of the three groups (<0.05, <0.01). After 2-week treatment, the differences were not significant in the morning blood pressure and its control rate in the patients of the three groups (all >0.05). In 4 and 6 weeks of treatment, the levels of the morning blood pressure in the No.2 acupuncture group were lower than those in the No.1 acupuncture group, and the results in the No.1 and No.2 acupuncture groups were all lower than those in the medication group (all <0.05). In the follow-up visit for 3 and 6 months separately, the differences were not significant in the morning blood pressure among the three groups (all >0.05). In 2, 4 and 6 weeks of treatment, the symptom scores reduced as compared with those before treatment in the three groups (all <0.05). The symptom scores in the No.1 and No.2 acupuncture groups were all lower than those in the medication group (all <0.05). The differences were not significant between the No.1 acupuncture group and the No.2 acupuncture group (all >0.05).

CONCLUSIONThe comprehensive treatment of acupuncture at Fengchi (GB 20) and Neck-Jiaji (EX-B 2) combined with acupuncture technique for activating blood circulation, eliminating wind and regulating the liver and spleen achieve the effects of reducing the morning blood pressure in the patients with essential hypertension, relieving the symptoms of hypertension such as headache, vertigo and tinnitus and the effects are better than those of the acupuncture technique for activating blood circulation, eliminating wind and regulating the liver and spleen.

Acupuncture Points ; Acupuncture Therapy ; Blood Pressure ; Combined Modality Therapy ; Essential Hypertension ; therapy ; Humans ; Nifedipine ; therapeutic use ; Treatment Outcome

The brain has very high energy requirements and consumes 20% of the oxygen and 25% of the glucose in the human body. Therefore, the molecular mechanism underlying how the brain metabolizes substances to support neural activity is a fundamental issue for neuroscience studies. A well-known model in the brain, the astrocyte-neuron lactate shuttle, postulates that glucose uptake and glycolytic activity are enhanced in astrocytes upon neuronal activation and that astrocytes transport lactate into neurons to fulfill their energy requirements. Current evidence for this hypothesis has yet to reach a clear consensus, and new concepts beyond the shuttle hypothesis are emerging. The discrepancy is largely attributed to the lack of a critical method for real-time monitoring of metabolic dynamics at cellular resolution. Recent advances in fluorescent protein-based sensors allow the generation of a sensitive, specific, real-time readout of subcellular metabolites and fill the current technological gap. Here, we summarize the development of genetically encoded metabolite sensors and their applications in assessing cell metabolism in living cells and in vivo, and we believe that these tools will help to address the issue of elucidating neural energy metabolism.
Animals ; Biosensing Techniques ; Brain ; cytology ; metabolism ; Cytological Techniques ; Energy Metabolism ; Humans ; Luminescent Proteins ; genetics ; metabolism ; Time Factors

Objective To investigate the type,clinical and imaging features of iatrogenic bile duct injury and the efficacy and safety of endoscopic and interventional radiology therapy.Methods A total of 48 patients with iatrogenic bile duct injury who have undergone endoscopic and/or interventional therapy from January 1st 2013 to June 30th 2016 were enrolled.Patients' general information,causes of injury,clinical manifestations,treatment methods,efficacy and complications were retrospectively analyzed.Results The causes of iatrogenic bile duct injury were cholecystectomy(45.8％,22/48),liver transplantation (35.4％,17/48),transjugular intrahepatic portosystemic shunt (8.3％,4/48),Roux-en-Y anastomosis (6.3％,3/48) and endoscopic retrograde cholangiopancreatography (4.2％,2/48).The most common type of iatrogenic bile duct injury was stenosis of intra/extra bile ducts (66.7％,32/48).Other types included biliary fistula(18.8％,9/48),hemobilia (10.4％,5/48) and stenosis of anastomotic stoma (4.2％,2/48).The most common clinical manifestations were jaundice (37.5％,18/48) and abdominal pain (29.2％,14/48).Other clinical manifestations were fever (14.6％,7/48),hematemesis or melena (8.3％,4/48) and abnormal drainage fluid (8.3％,4/48).Diagnosis was confirmed by angiography,cholangiography or endoscopy.The overall effective rate of minimally invasive therapy was 91.7％ (44/48) and the most common complications were fever (16.7％,8/48) and pancreatitis (10.4％,5/48).Other complications were hemobilia (2.1％,1/48),cardia dilaceration (2.1％,1/48) and biliary fistula caused by catheter shedding(2.1％,1/48).Conclusion Iatrogenic bile duct injury could occur after upper abdominal surgeries,endoscopic or interventional procedures.Early diagnosis and treatment with endoscopic or vascular interventional methods can achieve satisfying efficacy and safety.

Objective To study the clinical characteristics of gynura segetum induced hepatic sinusoidal obstruction syndrome (HSOS).Methods From July 2008 to October 2016,a total of 115 cases of gynura segetum caused HSOS were retrospectively analyzed.The history of taking gynura segetum before disease onset was recorded and epidemiologic data of main clinical symptoms,clinical manifestations,laboratory examinations,imaging and pathological features were observed.Results Among the 115 cases of HSOS,there were 113 patients with abdominal pain,106 with anorexia and 42 with jaundice sclera.A total of 108 patients displayed increased serum total bilirubin,41 of them only with mildly increased total bilirubin.There were 29 patients with albumin lower than 30 g/L,64 patients with prolonged prothrombin time (PT) and PT of 11 patients was prolonged for more than three seconds.Meanwhile,31 patients were with prolonged activated partial prothrombin time (APTT).A total of 60 patients had low platelet count.And 92 patients underwent ultrasound examination,among them,71 patients had enlarged liver size,79 patients with uneven internal echo of liver,70 patients with ascites,14 patients with patchy low echo tissue around hepatic venous.A total of 60 patient accepted computed tomography (CT) examination,and all of them had ascites,14 patients with mildly enlarged spleen and eight patients with gastro-esophageal varices.The results of CT plain scan indicated hepatomegaly,decreased liver density,map-like changes of patchy low density in delayed phase,heterogeneous enhancement of liver parenchyma in arterial phase,compression and deformation of liver segment of inferior vena cava and halo sign around venous portal vein.The results of pathological examination demonstrated the widening of hepatic sinusoid with hemorrhage and congestion,destruction of liver plate in zone Ⅲ area.There were seven patients who received hepatic venous pressure gradient (HVPG) measurement which were all significantly increased.Conclusions The characteristics of patients with gynura segetum caused HSOS are abdominal pain,anorexia and jaundice;mildly increased serum total bilirubin and albumim liver enlargement,slow blood velocity of portal vein and splenic veim increased HVPG,hepatic sinus congestion and cell coagulation necrosis in zone Ⅲ area.