The gut microbiota is regarded as the "eighth organ" of the human body and plays a critical regulatory role in the occurrence and progression of various diseases. Ulcerative colitis （UC） is a chronic inflammatory bowel disease with a complex etiology and a tendency toward recurrent episodes. In recent years， studies have shown that gut microbiota dysbiosis plays a key role in its pathological processes. Meanwhile， an increasing number of studies have demonstrated that imbalances in the gut microbiota and abnormalities in its metabolites are closely associated with the development of atrial fibrillation （AF）. Although UC and AF belong to diseases of the digestive system and cardiovascular system， respectively， both exhibit systemic inflammatory characteristics and are often accompanied by gut microbiota dysregulation and abnormal metabolic products. However， systematic investigations into the mechanisms by which gut microbiota-derived metabolites act in these two diseases remain limited. Based on this， the present study adopts literature review and theoretical analysis methods， taking the "gut microbiota-gut-heart" axis as the entry point， to systematically summarize the signaling networks of three key classes of metabolites， i.e.， short-chain fatty acids （SCFAs）， bile acids （BAs）， and trimethylamine N-oxide （TMAO）， in the comorbidity mechanism of UC and AF. The findings indicate that these metabolites may activate key inflammatory pathways， such as NF-κB and NLRP3， thereby synergistically mediating intestinal barrier dysfunction and systemic inflammation and constructing a potential comorbidity network. On this basis， potential intervention strategies for the treatment of UC-AF comorbidity， including probiotic intervention and fecal microbiota transplantation， are further discussed. This study aims to provide new theoretical evidence and research perspectives for prevention and treatment strategies of cross-system diseases.

OBJECTIVE To evaluate the effect of manipulation of Imipenem and cisplatin sodium （ICS） for injection on the consistency of its main drug imipenem （IPN） content， and the stability of different concentrations of ICS solution， to provide a reference for the safe and effective use of ICS in children. METHODS Three operators prepared ICS solutions according to the two commonly used dosage methods for children （10 mL or 20 mL 0.9% Sodium chloride injection to prepare the initial ICS solution and draw the required dose from the initial suspension）. The content of IPN was determined by ultra-high performance liquid chromatography-tandem mass spectrometry after parallel processing. The content consistency of solutions in each group was determined according to the coefficient of variation （CV）＜15% of the IPN content. ICS test solution X1 was prepared according to the instructions， and then test solutions X2 and X3 were prepared by diluting X1 with 0.9% Sodium chloride injection in the volume ratios of 1∶1 and 1∶2， which were stored at room temperature （[ 23.0±0.5） ℃]， in a thermostatic water bath at 30 ℃， and in a refrigerator at 2-8 ℃. The stability of the drug solution was determined by the ratio of the IPN mass concentration measured at the specified temperature and time to the initial （0 h） mass concentration （if the ratio was≥90%， it was considered that the drug solution was stable）. RESULTS CV of IPN content was ＜15% in each group of solutions prepared with two manipulation methods by each operator， indicating a small deviation in IPN content. The solutions at the three concentration levels were stable at room temperature for 6 h or refrigerated for 18 h. The test solutions X1 and X2 were also stable when placed at 30 ℃ for 6 h， but the IPN concentration in test solution X3 decreased by about 20% compared with that of 0 h. CONCLUSIONS The consistency of the content of IPN is good in the two commonly used methods for ICS manipulation in children. The stability of ICS solution is affected by concentration， temperature and time. Lower concentrations at higher temperatures resulted in decreased stability of IPN. Clinical attention should be paid to controlling the amount of solvent as well as temperature and time during preparation and use.

Objective To investigate the correlation between serum amyloid A(SAA)level and disease se-verity in children infected with severe acute respiratory syndrome coronavirus 2(COVID-19).Methods A to-tal of 116 children infected with COVID-19 admitted to the Department of Pediatrics of the hospital from De-cember 2022 to April 2023 were included and divided into asymptomatic/mild group and moderate/severe group according to the severity of the disease.In addition,65 healthy children who received health examination during the same period were selected as the control group.Serum SAA levels in children in acute stage and convalescent stage were detected by enzyme-linked immunosorbent assay.Results Compared with the control group,the serum SAA level in the children infected with COVID-19 was significantly increased in the acute stage(P＜0.05).The area under the receiver operating characteristic(ROC)curve(AUC)of SAA levels in the acute stage for diagnosing children with COVID-19 infection was 0.926(95％CI:0.886-0.966).In SARS-CoV-2 infected children,the SAA levels in the acute stage in the asymptomatic/mild group and the moderate/severe group were 2.71(1.29-10.86)mg/L and 37.78(18.58-92.62)mg/L,the differences were statistically significant between the two groups(Z=5.782,P＜0.001).In addition,serum SAA was pos-itively correlated with severity of SARS-CoV-2 by Spearman analysis(r=0.657,P＜0.001).Serum SAA lev-els were also significantly positively correlated with C-reactive protein(CRP),immunoglobulin(Ig)M,IgG,IgA and neutralizing antibody(NAb)in acute stage(P＜0.05).The AUC of serum SAA level in acute stage for diagnosing the moderate/severe children with SARS-CoV-2 was 0.889(95％CI:0.842-0.955),which was higher than that of CRP(P＜0.05).Compared with serum antibodies(IgM,IgG,IgA and NAb),the rate of serum SAA positive(≥5.55 mg/L)in children in acute stage was significantly higher(P＜0.05).The positive rate of serum SAA in convalescent children was significantly lower than that of serum antibody(P＜0.05).Conclusion Elevated serum SAA in acute phase is associated with increased risk of SARS-CoV-2 infec-tion and disease severity in children.Serum SAA is promising as a good biomarker for monitoring SARS-CoV-2 infection and severity in children.

Objective To identify genes regulated by ME2 and to explore their roles as well as underlying mecha-nisms in liver cancer progression.Methods RNA-seq data of siME2-transfected cells were subjected to differential expression analysis,clustering,GO and KEGG enrichment analyses.The mRNA level of the potential target gene SHCBP1 was measured by quantitative real-time PCR(qPCR)following ME2 knockdown or overexpression in HepG2 cells.The effect of ME2 and SHCBP1 on the downstream pathway was examined by Western blot.Cell pro-liferation,wound healing,and colony formation assays were conducted to evaluate SHCBP1's role in liver cancer cell proliferation and migration.Survival analysis of the TCGA-LIHC cohort was performed to determine the prog-nostic value of SHCBP1 in liver cancer patients.Results Differentially expressed genes in siME2-transfected cells were significantly enriched in biological processes including the PI3K-Akt signaling pathway,cell cycle,and serine phosphorylation.In HepG2 cells,ME2 knockdown led to a reduction in SHCBP1 mRNA level,whereas ME2 over-expression resulted in enhanced SHCBP1 mRNA level,demonstrating a positive correlation between ME2 and SHCBP1 expression.Western blot analysis revealed that ME2 enhanced PI3K-Akt signaling pathway activation through SHCBP1.qPCR results confirmed that SHCBP1 was significantly over-expressed in liver cancer cells and promoted both proliferation and migration,contributing to poor prognosis in liver cancer patients.Conclusions ME2 promotes liver cancer progression by regulating SHCBP1 to activate the PI3K-Akt signaling pathway,presen-ting a novel therapeutic target for liver cancer treatment.

Objective:To explore the value of dual-layer detector spectral CT quantitative parameters in evaluating the treatment response of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).Methods:The study was a cross-sectional study. From May 2021 to March 2023, a total of 52 patients with LARC who received complete nCRT and were pathologically confirmed rectal adenocarcinoma at the Guangdong Province Hospital of Traditional Chinese Medicine were retrospectively enrolled. Each patient underwent spectral CT examination before and after nCRT, including plain scan, arterial phase (AP), and venous phase (VP) scans. According to the tumor regression grade, the patients were divided into the good response ( n=20) and the poor response group ( n=32). Measurements of the primary tumor′s spectral CT parameters, including effective atomic number (Z eff) at plain scan, iodine concentration (IC), CT values of 40 keV and 100 keV virtual monochromatic image (VMI) at dual-enhanced phases, were taken before and after nCRT. Additionally, the normalized iodine concentration (NIC), spectral curve slope (λHU), and the change rate of the above parameters before and after nCRT were calculated. The independent sample t-test or Mann-Whitney U test was used to compare the differences between the two groups. The receiver operating characteristic (ROC) curve was used to assess the efficacy of various metrics in evaluating the tumor treatment response of nCRT. A binary logistic regression analysis of combined parameter results was performed for the parameters with the areas under curve (AUC)>0.75, and the AUC of the combined parameter was evaluated. Results:There were significant differences in NIC AP and λHU VP before nCRT, NIC VP and λHU VP after nCRT, and the change rates of Z eff, NIC AP, NIC VP and λHU AP between the good response group and the poor response group ( P<0.05). The remaining parameters showed no statistically significant difference ( P>0.05). The ROC curve results showed that the AUCs of the above 8 parameters for evaluating tumor treatment response of nCRT were 0.702, 0.655, 0.695, 0.769, 0.738, 0.807, 0.791, and 0.677, respectively. The AUC of the combined model of the three parameters with AUC>0.75 (λHU VP after nCRT, the change rate of NIC AP and NIC VP) was 0.869, with 80.0% sensitivity and 84.4% specificity. Conclusion:The quantitative parameters derived from spectral CT may provide new markers for evaluating the response to nCRT treatment in patients with LARC. The multi-parameter combined model can improve diagnostic efficacy.

BACKGROUND:Transcranial magneto-acoustical electrical stimulation(TMAES)is a non-invasive,high-precision neurofocused stimulation method based on magneto-acoustic coupling electrical effect,which can regulate the rhythmic oscillation of nerve activity,thereby affecting the brain's movement,cognition and other functions. OBJECTIVE:To explore the effect of TMAES on beta oscillations in the neural circuits of healthy rats and Parkinson's rats. METHODS:(1)Animal experiments:Twenty-four Wistar rats were randomly divided into four groups(n=6 per group).The rats in the normal control group received no intervention,while those in the normal stimulation group received TMAES(the average spatial peak pulse intensity:13.33 W/cm2,fundamental frequency:0.4 MHz,the number of fundamental wave cycles:1000,and pulse frequency:200 Hz).The model control group and model stimulation group were established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.After successful modeling,the rats in the model control group received sham TMAES stimulation in the prefrontal cortex,and those in the model stimulation group received TMAES in the prefrontal cortex,and the duration of stimulation was 2.0 minutes per day.After an interval of 8-10 minutes,the local field potential signals of rats were collected during the execution of T-maze test and the correct rate of behavior was recorded at the same time to compare and analyze the time-frequency distribution of local field potential signals and behavioral differences among the groups.The stimulation experiment and T-maze test were stopped when the correct rate of rats was higher than 80%for 3 consecutive days.(2)Modeling and simulation experiments:The cortical-basal ganglion circuit model under TMAES was established,and the ultrasonic emission period(5,10,20 ms),ultrasonic emission duty cycle(30%,50%,90%)and induced current density(20,50,100 μA/cm2)were changed respectively to compare the power spectral density values of beta oscillations in healthy rats and Parkinson's rats under different stimulation parameters. RESULTS AND CONCLUSION:(1)Animal experiments:The spatial learning ability of the rats in the normal control group was stronger than that of the model control group(P＜0.001),the spatial learning ability of the rats in the normal stimulation group was stronger than that of the normal control group(P＜0.05),and the spatial learning ability of the rats in the model stimulation group was stronger than that of the model control group(P＜0.01).The distribution of beta oscillation energy in the normal control group was more concentrated,and the beta oscillation signal energy was reduced in the normal stimulation group compared with the normal control group.The beta oscillation energy was widely distributed and the energy value was significantly higher in the model control group and the model stimulation group than the normal control and normal stimulation groups.Moreover,the beta oscillation signal energy in the model stimulation group was significantly lower than that in the model control group.(2)Modeling and simulation experiments:the peak power spectral density of the beta band of healthy rats without stimulation(30 dB)was significantly lower than that of Parkinson's rats(55 dB).The power spectral density value generally decreased after stimulation.The peak power spectral density in the beta band was positively correlated with the ultrasonic emission period and negatively correlated with the induced current density.In addition,the peak power spectral density value was the lowest when the duty cycle of ultrasonic emission was 50%.These findings indicate that TMAES suppresses beta oscillations in healthy and Parkinson's disease rats,thereby improving motor function and decision-making cognitive function in rats.

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

Objective To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. Methods The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. Results No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05). Conclusions The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.

Objective:To analyze the clinical data of patients with end-stage ankle and hindfoot ar-thropathy who underwent tibiotalocalcaneal(TTC)arthrodesis by the same surgeon,explore the short-and mid-term clinical results,complications and functional improvement,and discuss the clinical progno-sis and precautions of TTC arthrodesis.Methods:Retrospective analysis was made on the clinical data of 40 patients who underwent TTC arthrodesis by the same surgeon from March 2011 to December 2020.In this study,23 males and 17 females were included,with an average age of(49.1±16.0)years.All the patients underwent unilateral surgery.The clinical characteristics,imaging manifestations,main diagno-sis and specific surgical techniques of the patients were recorded.The clinical outcomes were evaluated by comparison of the American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot score and visual analogue scale(VAS)between pre-operation and at the last follow-up.The fusion healing time,symptom improvement(significant improvement,certain improvement,no improvement or deterioration)and postoperative complications were also recorded.Results:The median follow-up time was 38.0(26.3,58.8)months.The preoperative VAS score was 6.0(4.0,7.0),and the AOFAS score was 33.0(25.3,47.3).At the last follow-up,the median VAS score was 0(0,3.0),and the AOFAS score was 80.0(59.0,84.0).All the significantly improved compared with their preoperative corre-sponding values(P＜0.05).There was no wound necrosis or infection in the patients.One patient suf-fered from subtalar joint nonunion,which was syphilitic Charcot arthropathy.The median bony healing time of other patients was 15.0(12.0,20.0)weeks.Among the included patients,there were 25 cases with significant improvement in symptom compared with that preoperative,8 cases with certain improve-ment,4 cases with no improvement,and 3 cases with worse symptoms than that before operation.Con-clusion:TTC arthrodesis is a reliable method for the treatment of the end-stage ankle and hindfoot ar-thropathy.The function of most patients was improved postoperatively,with little impact on daily life.The causes of poor prognosis included toe stiffness,stress concentration in adjacent knee joints,nonunion and pain of unknown causes.