Objective To explore the casual relationship between immune cells and chronic pancreatitis(CP)using Mendelian randomization(MR)analysis.Methods The immune cell phenotypes and CP GWAS data used in this study were obtained from public databases,and 731 immune cell phenotypes were included.The bidirectional MR analysis was used to explore the causal relationship between immune cells and CP,and various sensitivity analysis methods were used to verify the heterogeneity and level multiplicity of the results.Results This study identified 33 immune cell phenotypes with a causal relationship with CP,of which 18 were inhibitory factors,and the rest were risk factors.Among the 18 inhibitory factors,CD25 on CD4+in the Treg cell group showed the most significant inhibitory effect.Among the 15 risk factors,CD8br AC in the TBNK cell group,CD8br on TD CD8br in the mature T cell group,and CD39+CD8br％ T cell and CD28 on CD4+in the Treg cell group showed statistical significance.The reverse MR results further confirmed the unidirectionality of the causal relationship.Conclusion Our study revealed the close relationship between immune cells and CP through MR method,highlighting the complex interaction pattern between the immune system and CP.

Objective:To compare the efficacy of in situ repair and conversion to full-thickness repair in patients with partial tears of the supraspinatus tendon bursa side in rotator cuff tears. Methods:A retrospective analysis was performed on 81 patients who underwent shoulder arthroscopic surgery due to Ellman grade III partial tears on the rotator cuff bursa side in Beijing Friendship Hospital, Capital Medical University from January 2021 to December 2022, according to the different intraoperative supraspinatus tendon repair methods, the patients were divided into the in situ repair group ( n=44) and the partial-to-full-thickness repair group ( n=37). Patients in the in situ repair group were treated with in situ repair for supraspinatus tendon repair, while those in the partial-to-full-thickness repair group were treated with partial-to-full-thickness repair for supraspinatus tendon repair. The general information, pain visual analogue scale (VAS) score, University of California, Los Angeles (UCLA) shoulder joint score and Constant score of the patients were compared and analyzed; the operation time, number of anchors used, and rotator cuff re-tear rate 1 year after surgery were compared and analyzed. The measurement data were expressed as mean ± standard deviation ( ± s), and comparisons between groups were performed using the independent samples t-test. The count data were expressed as the number of cases and percentages, and comparisons between groups were performed using the Chi-square test. Results:All 81 patients completed the follow-up. One year after surgery, the pain VAS scores of the in situ repair group and the partial-to-full-thickness repair group were 1.48±1.07 and 1.38±0.83, respectively, with no significant statistical difference ( P=0.647). The UCLA shoulder joint score and Constant score in the in situ repair group were 30.09±1.46 and 83.05±10.94, respectively, and those in the partial-to-full-thickness repair group were 30.46±1.04 and 84.95±9.20, respectively, there were no significant statistical difference ( P=0.203, 0.405). There was no significant statistical difference in the operation time between the in situ repair group and the partial-to-full-thickness repair group ( P=0.276), but the partial-to-full-thickness repair group was about 11.5 min slower on average. The number of anchors used in the in situ repair group (1.86±0.88) was significantly less than that in the partial-to-full-thickness repair group (2.51±0.65), and the difference was statistically significant ( P<0.001). There was no significant statistical difference in the re-tear rate between the two groups 1 year after surgery ( P=0.625). Conclusions:For patients with partial tears of the supraspinatus tendon bursa side in rotator cuff tears, both in situ repair and partial-to-full-thickness repair can achieve good clinical results, but conversion to full-thickness repair requires longer operation time and more anchors. The choice of specific surgical method needs to be determined based on the patient′s condition and the doctor′s technical proficiency.

Objective:To evaluate the causal relationship between autism spectrum disorder (ASD) and chronic pancreatitis (CP) using a bidirectional two-sample Mendelian randomization (MR) analysis.Methods:Based on genome-wide association study (GWAS) data, forward and reverse two-sample MR analyses were conducted to examine the causal relationship between ASD and CP. Single-nucleotide polymorphisms (SNPs) reaching genome-wide significance were selected from the GWAS data as candidate instrumental variables, and the Steiger directionality test was used to confirm the causal direction. The inverse-variance weighted (IVW) method was applied as the primary analysis to estimate the causal effect of the exposure on the outcome. MR-Egger regression and weighted median methods were used as supplementary sensitivity analyses to assess the robustness of the results. Pleiotropy and heterogeneity tests were performed to evaluate the reliability of the findings.Results:The forward MR analysis ultimately identified 29 SNPs. The IVW analysis indicated that ASD had a significant positive causal effect on CP risk ( OR=1.197, 95% CI 1.047-1.368, P=0.008), with no evidence of horizontal pleiotropy or significant heterogeneity. In the reverse MR analysis, 17 SNPs were included; the IVW analysis did not detect a significant causal effect of CP on ASD ( OR=0.990, 95% CI 0.935-1.047, P=0.717), also with no evidence of horizontal pleiotropy or significant heterogeneity. Causal effect estimates from MR-Egger regression and weighted median analyses were generally consistent with those of IVW. Conclusions:These findings indicate that, at the level of genetic susceptibility, ASD is a risk factor for CP.

Objective To explore the casual relationship between immune cells and chronic pancreatitis(CP)using Mendelian randomization(MR)analysis.Methods The immune cell phenotypes and CP GWAS data used in this study were obtained from public databases,and 731 immune cell phenotypes were included.The bidirectional MR analysis was used to explore the causal relationship between immune cells and CP,and various sensitivity analysis methods were used to verify the heterogeneity and level multiplicity of the results.Results This study identified 33 immune cell phenotypes with a causal relationship with CP,of which 18 were inhibitory factors,and the rest were risk factors.Among the 18 inhibitory factors,CD25 on CD4+in the Treg cell group showed the most significant inhibitory effect.Among the 15 risk factors,CD8br AC in the TBNK cell group,CD8br on TD CD8br in the mature T cell group,and CD39+CD8br％ T cell and CD28 on CD4+in the Treg cell group showed statistical significance.The reverse MR results further confirmed the unidirectionality of the causal relationship.Conclusion Our study revealed the close relationship between immune cells and CP through MR method,highlighting the complex interaction pattern between the immune system and CP.

Objective:To evaluate the causal relationship between autism spectrum disorder (ASD) and chronic pancreatitis (CP) using a bidirectional two-sample Mendelian randomization (MR) analysis.Methods:Based on genome-wide association study (GWAS) data, forward and reverse two-sample MR analyses were conducted to examine the causal relationship between ASD and CP. Single-nucleotide polymorphisms (SNPs) reaching genome-wide significance were selected from the GWAS data as candidate instrumental variables, and the Steiger directionality test was used to confirm the causal direction. The inverse-variance weighted (IVW) method was applied as the primary analysis to estimate the causal effect of the exposure on the outcome. MR-Egger regression and weighted median methods were used as supplementary sensitivity analyses to assess the robustness of the results. Pleiotropy and heterogeneity tests were performed to evaluate the reliability of the findings.Results:The forward MR analysis ultimately identified 29 SNPs. The IVW analysis indicated that ASD had a significant positive causal effect on CP risk ( OR=1.197, 95% CI 1.047-1.368, P=0.008), with no evidence of horizontal pleiotropy or significant heterogeneity. In the reverse MR analysis, 17 SNPs were included; the IVW analysis did not detect a significant causal effect of CP on ASD ( OR=0.990, 95% CI 0.935-1.047, P=0.717), also with no evidence of horizontal pleiotropy or significant heterogeneity. Causal effect estimates from MR-Egger regression and weighted median analyses were generally consistent with those of IVW. Conclusions:These findings indicate that, at the level of genetic susceptibility, ASD is a risk factor for CP.

Objective To construct and validate an effective prognostic nomogram for the patients with incidental gallbladder cancer(IGBC).Methods The clinical data of 161 patients with IGBC requiring radical surgery admitted to the First Affiliated Hospital of Xi'an Jiaotong University from May 2011 to October 2022 was analyzed retrospectively.COX proportional risk regression model was used to screen for influencing factors on overall survival(OS)of IGBC.Nomogram was constructed based on independent influencing factors that affected the prognosis of IGBC patients.The concordance index(C-index)and calibration curve were used to validate the performance of the model.Receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA)were used to validate the predictive accuracy and net benefit of the plotted column chart.Results Univariate COX regression analysis suggested that age,T stage,N stage,M stage,preoperative carcinoembryonic antigen(CEA),preoperative carbohydrate antigenl9-9(CA19-9),preoperative red blood cell volume distribution on width coefficient of variation(RDW-CV),treatment method,and recurrence and metastasis were risk factors which affected the long-term survival of IGBC patients after radical surgery.Multivariate COX regression analysis suggested that T stage,N stage,preoperative CA19-9,preoperative RDW-CV,preoperative AST,treatment methods,and recurrence and metastasis were independent risk factors which affected the prognosis of IGBC patients.The C-index of the constructed prognostic model was 0.872.The calibration plot demonstrated good performance of the Nomogram.ROC curve analysis showed an area under the curve of 0.869,confirming a high sensitivity and specificity.A high net benefit was proven by DCA.Conclusions The constructed Nomogram.can accurately and intuitively predict the survival probability of IGBC patients after radical surgery.

【Objective】 To explore the causal relationship between education level and pancreatitis risk through Mendelian randomization. 【Methods】 A two-sample Mendelian randomization analysis was conducted using genome-wide association study (GWAS) summary data. The GWAS data for education level and pancreatitis were obtained from SSGAC database and the FinnGen database (version R9). Causal relationship between education level and pancreatitis was explored using the inverse variance weighted (IVW), MR-Egger, and weighted median methods. Heterogeneity and directional pleiotropy were evaluated using Cochran’s Q test and funnel plots. 【Results】 Totally 604 SNPs associated with education level were included. The results provided evidence that there was negative relationship between education level and pancreatitis risk. For acute pancreatitis, OR=0.52, 95% CI: 0.44-0.62, P=2.43×10^-14 while for chronic pancreatitis, OR=0.51, 95% CI: 0.41-0.64, P=7.20×10^-9. Results from MR-Egger and weighted median analyses obtained the same results. The results of sensitivity analysis indicated that this study did not violate the basic assumptions of Mendelian randomization. 【Conclusion】 There is a causal relationship between education level and the occurrence of pancreatitis. The educational level is negatively correlated with the risk of pancreatitis.

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.
Rats ; Animals ; Doxorubicin/adverse effects* ; Nephrotic Syndrome ; AMP-Activated Protein Kinases/metabolism* ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

OBJECTIVE: To investigate the correlation of procalcitonin (PCT), interleukin-6 (IL-6) and antithrombin III (AT III) with the severity of sepsis, and to compare the predictive value of the above indicators alone or in combination. METHODS: A retrospective cohort study was conducted. Eighty-five patients with sepsis admitted to the department of intensive care medicine of Shandong Provincial Hospital Affiliated to Shandong First Medical University from April 2021 to September 2022 were enrolled. General information, sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluation II (APACHE II) score within 24 hours of admission, inflammatory indicators [PCT, IL-6, serum amyloid A (SAA), neutrophil to lymphocyte ratio (NLR), and C-reactive protein (CRP)] and coagulation indicators (D-dimer and AT III) levels at admission, and 28-day prognosis were collected. The differences of the above indicators were compared among patients with different prognosis at 28 days and different severity of sepsis. The correlation between PCT, IL-6, AT III and the severity of sepsis was analyzed by Spearman rank correlation method. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCT, IL-6 and AT III alone or in combination on the 28-day death of patients with sepsis. RESULTS: Eighty-five patients were enrolled finally, 67 cases survived and 18 cases died at 28 days. The mortality was 21.2%. There were no statistical significant differences in gender, age and other general data between the two groups. The patients in the death group were more serious than those in the survival group, and PCT, IL-6, and CRP levels were significantly higher than those in the survival group [PCT (μg/L): 4.34 (1.99, 14.42) vs. 1.17 (0.31, 3.94), IL-6 (ng/L): 332.40 (50.08, 590.18) vs. 61.95 (31.64, 194.20), CRP (mg/L): 149.28 (75.34, 218.60) vs. 83.23 (48.22, 174.96), all P < 0.05], and AT III activity was significantly lower than that in the survival group [(53.67±28.57)% vs. (80.96±24.18)%, P < 0.01]. However, there were no significant differences in D-dimer, NLR and SAA between the two groups. Among the 85 patients, 36 had sepsis with single organ dysfunction, 29 had sepsis with multiple organ dysfunction, and 20 had septic shock with multiple organ dysfunction. With the increase of the severity of sepsis, PCT and IL-6 levels gradually increased [PCT (μg/L): 0.36 (0.19, 1.10), 3.00 (1.22, 9.94), 4.34 (2.18, 8.86); IL-6 (ng/L): 43.99 (20.73, 111.13), 100.00 (45.37, 273.00), 332.40 (124.4, 693.65)], and the activity of AT III decreased gradually [(89.81±21.42)%, (71.97±24.88)%, and (53.50±25.41)%], all with statistically significant differences (all P < 0.01). Spearman rank correlation analysis showed that PCT and IL-6 levels in sepsis patients were significantly positively correlated with the severity of the disease (r values were 0.562 and 0.517, respectively, both P < 0.01), and AT III activity was significantly negatively correlated with the severity of the disease (r = -0.523, P < 0.01). ROC curve analysis showed that PCT, IL-6, and AT III alone or in combination had some predictive value for the death of sepsis patients at 28 days. The area under the ROC curve (AUC) of the above three indicators in combination was higher than that of the individual tests (0.818 vs. 0.722, 0.725, and 0.770), with a sensitivity of 83.3% and a specificity of 73.1%. CONCLUSIONS PCT, IL-6, and AT III were significantly correlated with the severity of sepsis patients. The combined assay of the above three indicators can effectively improve the prediction of the prognosis of sepsis patients.
Humans ; Procalcitonin ; Interleukin-6 ; Antithrombin III ; Retrospective Studies ; Multiple Organ Failure ; ROC Curve ; Sepsis/diagnosis* ; Prognosis ; C-Reactive Protein/analysis* ; Anticoagulants

Objective:To investigate the influence of childhood traumatic experience on internet addiction of adolescents and the mediating effect of self-concealment.Methods:Childhood trauma questionnaire(CTQ), self-concealment scale(SCS) and adolescent pathological internet use scale(APIUS) were used to investigate 532 college students.SPSS 22.0 was used for descriptive statistics, correlation analysis and regression analysis.Amos 24.0 was used for confirmatory factor analysis, and the relevant assumptions were verified through structural equation model.Results:The total scores of childhood abuse, self-concealment and adolescent pathological internet use were (37.23±11.91), (26.09±9.26) and (82.15±28.09), respectively.Correlation analysis showed that childhood trauma was positively correlated with self-concealment ( r=0.27, P<0.01). Self-concealment was positively correlated with internet addiction ( r=0.47, P<0.01). Childhood trauma was positively correlated with internet addiction ( r=0.36, P<0.01). Mediating effect test showed that childhood trauma had a significant positive predictive effect on self-concealment ( β=0.34, P<0.01), self-concealment had a significant positive predictive effect on internet addiction ( β=0.34, P<0.01), and childhood trauma had a direct predictive effect on internet addiction ( β=0.31, P<0.01). Conclusion:Childhood trauma and self-concealment have significant influence on internet addiction, and self-concealment plays a partial mediating role between childhood trauma and internet addiction of adolescents.