ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

Objective To investigate the correlation between CT parameters of erector spinae muscle(ESM)and pulmonary function in elderly patients with chronic obstructive pulmonary disease(COPD),and to analyze its predictive value for the prognosis of patients.Methods A total of 120 COPD patients were included as the case group(including 60 cases in stable stage and 60 cases in acute exacerbation stage),and 60 smokers were selected as the control group.The differences of ESM CT parameters and pulmonary function parameters in each group were compared.According to the prognosis of COPD,patients were divided into good prognosis group(n=106)and poor prognosis group(n=14),and the predictive efficacy of ESM CT parameters on the prognosis of COPD patients was analyzed.Results The pulmonary function parameters,ESM cross sectional area(CSA)(ESMCSA)and ESM local volume in the case group were significantly lower than those in the control group(P<0.05).ESMCSA and ESM local volume were positively correlated with inspiratory capacity(IC),vital capacity(VC),forced vital capacity(FVC)and forced expiratory volume in one second(FEV1)(P<0.001).The average muscle density of ESM was positively correlated with IC,VC and FVC(P<0.05),but not with FEV1.The area under the curve(AUC)of ESMCSA and ESM local volume in predicting poor prognosis of COPD patients was 0.769[95%confidence interval(CI)0.661-0.876]and 0.827(95%CI 0.734-0.919),respectively.Conclusion There is a certain correlation between the CT parameters of ESM and the pulmonary function parameters of COPD patients,among which the ESMCSA and the ESM local volume have high predictive efficacy for the prognosis of COPD patients.

Objective To observe the value of dual-energy CT(DECT)radiomics combined with clinical and CT features for predicting differentiation degree of gastric adenocarcinoma(GAC).Methods Totally 254 patients with GAC were prospectively analyzed and divided into high-grade group(low differentiation GAC,n=88)and low-grade group(middle-high differentiation GAC,n=166)according to pathological results.The patients were also divided into training set(n=203,including 70 high-grade and 133 low-grade GAC)and verification set(n=51,including 18 high-grade and 33 low-grade GAC)at the ratio of 8∶2.Radiomics features were extracted and screened based on venous phase single-level(40,70,100 and 140 keV)DECT,and a multi-energy radiomics model was constructed to predict GAC classification.Univariate analysis and multivariate logistic regression were used to analyze clinical and CT features as well as DECT parameters in training set to construct a clinic-CT model.Then a combined model was constructed through combining clinic-CT model with radiomics model.The predictive efficacy of the models were evaluated,and the calibration degree of the combined model was assessed.Results The area under the curve(AUC)of clinic-CT model,multi-energy radiomics model and combined model was 0.74,0.75 and 0.78 in training set,and 0.73,0.77 and 0.78 in verification set,respectively.Except for AUC of combined model was higher than that of clinic-CT model in training set(P＜0.05),no significant difference of AUC was found among models in training set nor verification set(all P＞0.05).The calibration degree of combined model was good in both training set and verification set(both P＞0.05).Conclusion DECT radiomics combined with clinical and CT features could effectively predict differentiation degree of GAC.

Objective To investigate the expression levels of plasma circular RNA PTP4A2(circPTP4A2)and circTLK2 in elderly patients with acute ischemic stroke(AIS)and their predic-tive value for neurological functional outcomes.Methods A total of 122 elderly AIS patients admitted to our department from May 2021 to December 2022 were prospectively recruited,and according to their modified Rankin Scale(mRS)score at 3 months after stroke onset,they were divided into a good outcome group(mRS score≤2,81 cases)and a poor outcome group(mRS score:3-6,41 cases).Their baseline data,and plasma circPTP4A2 and circTLK2 levels were compared between the two groups.Multivariate logistic regression analysis was employed to iden-tify prognostic factors for poor outcomes in the elderly AIS patients.ROC curve analysis was ap-plied to evaluate the prognostic value of circPTP4A2 and circTLK2 for adverse outcomes in the patients.Pearson correlation analysis was performed to assess the relationship of plasma levels of circPTP4A2 and circTLK2 with NIHSS score,as well as mRS score.Results The plasma expres-sion levels of circPTP4A2 and circTLK2 were significantly higher in the poor outcome group than the good outcome group[2.08(0.87,2.77)vs 0.93(0.63,1.20),1.71(0.92,2.80)vs 0.75(0.49,1.09),P＜0.01].Multifactor logistic regression analysis showed that plasma circPTP4A2 and circTLK2 were independent predictive factors for poor functional outcomes in elderly AIS patients(P＜0.01,P＜0.05).ROC curve analysis demonstrated that the AUC value of combined circPTP4A2 and circTLK2 in predicting poor outcome in elderly AIS patients was 0.787(95％CI:0.691-0.883).Pearson correlation analysis revealed that the expression levels of circPTP4A2 and cir-cTLK2 in elderly AIS patients were mildly positively correlated with baseline NIHSS scores(r=0.463,r=0.456;P＜0.01)and moderately positively correlated with mRS scores at 3 months after stroke onset(r=0.682,r=0.604;P＜0.01).Conclusion Plasma circPTP4A2 and circTLK2 may be potential biomarkers for predicting neurological functional outcomes in elderly AIS patients.

OBJECTIVES: Observational studies have suggested an association between preterm birth and stroke in late adulthood, but it remains unclear whether the association is causal. The purpose of this study was to evaluate the causal effects of gestational age on stroke and to determine the pathophysiological mechanisms underlying the causal associations. METHODS: Two-sample Mendelian randomization (MR) was performed to assess the causal effects of fetal gestational duration, early preterm birth (EPB), preterm birth, or postterm birth on stroke and its subtypes. Two-step Mendelian randomization (TSMR) and multivariable Mendelian randomization (MVMR) were additionally used to determine the role of common stroke risk factors, including cardiovascular diseases, hypertension, pulmonary impairment, inflammation, and metabolic diseases, in mediating the causal associations between gestational age and stroke and its subtypes. RESULTS: Genetically predicted EPB increased the risk of cardioembolic stroke (CES; odds ratio [OR], 1.115; 95% confidence interval [CI], 1.036 to 1.200; p=0.004) and large artery stroke (LAS; OR, 1.131; 95% CI, 1.031 to 1.241; p=0.009). The TSMR results showed that EPB was associated with a lower forced expiratory volume in the first second and forced vital capacity ratio (FEV1/FVC) (β=-0.020; 95% CI, -0.035 to -0.005; p=0.009), which increased the risk of CES and LAS. Further MVMR analysis showed that the associations between EPB and stroke disappeared after adjustment for FEV1/FVC. CONCLUSIONS Our data demonstrate that EPB is causally associated with an elevated risk of CES and LAS, and that pulmonary dysfunction mediates the causal impact of EPB on CES and LAS.

Objective:To investigate the effects of mixed probiotics on food allergy and the underlying mechanism.Methods:BALB/c mice on the 15 th day of pregnancy were randomly (random number table method) classified into the control group, food allergy model group and mixed probiotics group.Mice in the food allergy model and mixed pro-biotics group were subjected to ovalbumin (OVA) sensitization after birth, and those in the mixed probiotics group were then given probiotic solution by gavage from day 21 to day 35.Mice in control group were similarly given 9 g/L saline.Twenty-four hours after the last OVA sensitization, intestinal histopathological sections were prepared to observe intestinal pathological changes.Blood smears were prepared to detect eosinophil count.In addition, serum samples were collected to measure cytokine levels and OVA specific antibodies.The number of dendritic cells (DCs) and regulatory T cells (Tregs) in mouse mesenteric lymph nodes was calculated.Differences among 3 groups were compared by the One- Way ANOVA or Kruskal- Wallis H test. Results:Compared with those of food allergy model group, diarrhea score, the ratio of eosinophils and serum levels of interleukin(IL)-4, IL-5, IL-13, mast cell protease 1 (MCPT-1), and OVA specific antibodies IgE and IgG were significantly lower in mixed probiotics group[(2.00±0.71) points vs.(3.22±0.97) points, (2.28±1.61)% vs.(10.99±2.26)%, (413.68±22.81) ng/L vs.(708.78±27.66) ng/L, (36.64±3.74) ng/L vs.(46.05±4.95) ng/L, (201.37±65.61) ng/L vs.(495.22±96.66) ng/L, (31 924.15±1 177.77) ng/L vs.(36 175.77±618.29) ng/L, (9.10±8.08) ng/L vs.(19.69±0.84) ng/L, (30.50±8.81) ng/L vs.(190.32±6.40) ng/L], while IL-10 level was significantly higher[(164.12±3.88) ng/L vs.(123.90±7.31) ng/L] ( t=3.37, 8.72, 16.07, 3.90, 7.40, 7.95, 3.91, 44.00 and 7.76, respectively, all P<0.01). Compared with those of food allergy model group, programmed cell death ligand 1 (PD-L1) level on the surface of CD 103+ DCs and CD 103+ CD 80-CD 40-DCs, the proportion of Tregs in CD4 + T cells, and the level of programmed cell death 1 (PD-1) on the surface of Tregs were significantly higher in mixed probiotics group[(75.59±0.45)% vs.(45.60±4.73)%, (67.56±1.87)% vs.(37.12±6.07)%, (8.24±0.69)% vs.(6.20±0.66)%, (11.25±3.12)% vs.(4.08±2.33)%]( t=7.88, 4.48, 3.63 and 3.71, all P<0.01). Conclusions:Mixed probiotics can alleviate the symptoms of food allergy and inflammatory response of young rats through mediating Tregs via the PD-1/PD-L1 pathway.

Transketolase (EC 2.2.1.1, TK) is a thiamine diphosphate-dependent enzyme that catalyzes the transfer of a two-carbon hydroxyacetyl unit with reversible C-C bond cleavage and formation. It is widely used in the production of chemicals, drug precursors, and asymmetric synthesis by cascade enzyme catalysis. In this paper, the activity of transketolase TKTA from Escherichia coli K12 on non-phosphorylated substrates was enhanced through site-directed saturation mutation and combined mutation. On this basis, the synthesis of tartaric semialdehyde was explored. The results showed that the optimal reaction temperature and pH of TKTA_M (R358I/H461S/R520Q) were 32 ℃ and 7.0, respectively. The specific activity on d-glyceraldehyde was (6.57±0.14) U/mg, which was 9.25 times higher than that of the wild type ((0.71±0.02) U/mg). Based on the characterization of TKTA_M, tartaric acid semialdehyde was synthesized with 50 mmol/L 5-keto-d-gluconate and 50 mmol/L non-phosphorylated ethanolaldehyde. The final yield of tartaric acid semialdehyde was 3.71 g with a molar conversion rate of 55.34%. Hence, the results may facilitate the preparation of l-(+)-tartaric acid from biomass, and provide an example for transketolase-catalyzed non-phosphorylated substrates.
Escherichia coli/genetics* ; Transketolase/chemistry* ; Tartrates ; Escherichia coli Proteins/genetics*

CaMKII is essential for long-term potentiation (LTP), a process in which synaptic strength is increased following the acquisition of information. Among the four CaMKII isoforms, γCaMKII is the one that mediates the LTP of excitatory synapses onto inhibitory interneurons (LTP_E→I). However, the molecular mechanism underlying how γCaMKII mediates LTP_E→I remains unclear. Here, we show that γCaMKII is highly enriched in cultured hippocampal inhibitory interneurons and opts to be activated by higher stimulating frequencies in the 10-30 Hz range. Following stimulation, γCaMKII is translocated to the synapse and becomes co-localized with the postsynaptic protein PSD-95. Knocking down γCaMKII prevents the chemical LTP-induced phosphorylation and trafficking of AMPA receptors (AMPARs) in putative inhibitory interneurons, which are restored by overexpression of γCaMKII but not its kinase-dead form. Taken together, these data suggest that γCaMKII decodes NMDAR-mediated signaling and in turn regulates AMPARs for expressing LTP in inhibitory interneurons.
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Hippocampus/metabolism* ; Interneurons/physiology* ; Long-Term Potentiation/physiology* ; N-Methylaspartate/metabolism* ; Receptors, AMPA/physiology* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Synapses/physiology*

Objective:To study the relationship between pancreaticobiliary maljunction (PBM) with cholangiopancreatic diseases, and to evaluate the efficacy and safety using endoscopic therapy for PBM.Methods:The clinical data of 734 patients treated with ERCP at the Affiliated Hospital of Guizhou Medical University from May 2016 to April 2020 were analyzed retrospectively. Of 31 PBM patients who were finally included in this study, there were 23 patients with benign diseases and 8 patients with malignant diseases. Using the diameter of bile duct, these patients were divided into two groups: dilated bile duct group and the non-dilated bile duct group. The general characteristics of patients, incidences of cholangiopancreatic disease, endoscopic treatment, therapeutic efficacy and follow-up data were analyzed.Results:Of the 31 patients with PBM, 11 were males and 20 were females, aged (56.7±16.2) years. There were 4 patients with choledochal cyst (12.9%) and 6 patients with biliary cancer (19.4%). The incidences were significantly higher than those in non-PBM patients (0.9% and 5.3%, respectively, P<0.05). All 31 patients with PBM underwent endoscopic EST treatment, including 15 patients (48.4%) treated with endoscopic naso-biliary drainage (ENBD), 9 patients (29.0%) with endoscopic retrograde biliary drainage (ERBD), 4 patients (12.9%) with endoscopic papillary balloon dilatation (EPBD)+ ENBD, 1 patient (3.2%) with endoscopic metal biliary endoprothesis (EMBE)+ ENBD, 1 patient with ERBD+ endoscopic retrograde pancreatic drainage (3.2%), and 1 patient with EPBD+ ERBD+ EMBE (3.2%). The operative success rate was 100%. Serum AST, ALT, ALP, GGT, TBil and DBil levels of patients in the benign group and malignant group were significantly decreased postoperatively when compared with the preoperative levels (all P<0.05). One patient (3.2%) developed post ERCP pancreatitis. The preoperative and postoperative NRS scores of the patients in the benign group were 7(6, 8) points compared to 0 (0, 1) points, respectively ( P<0.05). All the 23 patients in the benign group were followed up for (25.13±12.90) months. There were no patients who were loss to follow-up. There was no malignant transformation. Three PMB patients with dilated bile ducts still had attacks of abdominal pain or jaundice. The symptoms of the remaining 20 patients were completely relieved, giving a treatment efficacious rate of 87.0% (20/23). Conclusions:PBM was closely related to choledochal cysts, biliary cancer and other diseases. Endoscopic treatment was efficacious and safe, and provided a safe and feasible treatment in preventing future cholangiopancreatic attacks.

Objective:To explore the application effect of Jiankuai psychosomatic active therapy in the elderly perioperative patients.Methods:From March 2018 to December 2019, 387 elderly patients in the urology department of the First People′s Hospital of Lianyungang City, Jiangsu Province were selected. According to the patients in two medical groups in the same ward, 193 patients in one medical group were divided into the experimental group and 194 patients in two medical groups as the control group. The experimental group was intervened by routine perioperative nursing combined with simple and fast psychosomatic active therapy, while the control group was only intervened by routine perioperative nursing. Self rating Anxiety Scale (SAS), Rosenberg Self-confidence Scale and General Self-efficacy Scale (GSEs) were used as the evaluation indexes before and after the implementation of the two groups.Results:The SAS score of the experimental group was 31.13 ± 3.64 and that of the control group was 48.45 ± 7.72 on the 7th day after operation. The difference between the two groups was statistically significant ( t value was 16.36, P < 0.05). The effective rate of self-confidence was 98.4% (190/193) and 94.8% (183/193) in the experimental group and 86.6% (168/194) and 85.1% (165/194) in the control group on the first day and the seventh day after operation, respectively. The difference between the two groups was statistically significant ( Z values were - 3.27 and 14.66, all P < 0.05). The GSEs score of the patients in the experimental group was 26.79 ± 2.17 and that of the control group was 16.86 ± 1.90. The difference between the two groups was statistically significant ( t value was 10.19, P < 0.05). Conclusions:The application of Jiankuai psychosomatic active therapy can effectively reduce the tension and anxiety of the elderly patients during the perioperative period, increase their self-confidence and self-efficacy, effectively improve the communication efficiency between doctors and patients, and promote rehabilitation.