ObjectiveTo investigate the value of baseline red cell distribution width （RDW） and alkaline phosphatase （ALP） level after ursodeoxycholic acid （UDCA） treatment for one month in predicting the response to UDCA treatment in patients with primary biliary cholangitis （PBC）. MethodsA retrospective analysis was performed for the data of 127 patients with PBC who were diagnosed in Department of Hepatology， The Third People’s Hospital of Jiangsu University， from January 2015 to July 2022， with data collected at baseline， after one month of treatment， and after one year of follow-up. Based on the Paris-I criteria， the patients were divided into good response group and poor response group， and the two groups were analyzed in terms of clinical and laboratory features and their association with response to UDCA. The Logistic regression method was used to investigate the independent risk factors for response to UDCA treatment. The area under the ROC curve （AUC） was used to determine the optimal cut-off values of related indicators； the patients were divided into two groups based on such values， and the two groups were compared in terms of baseline indicators and response. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the good response group， the poor response group had significantly higher levels of total bilirubin， aspartate aminotransferase/alanine aminotransferase， ALP， RDW， and RDW-CV at baseline and a significantly higher level of ALP after one month of UDCA treatment （Z=-4.792， -3.697， -2.399， -4.102， -3.220， and -4.236， all P<0.05）. Compared with the good response group， the poor response group had significantly lower levels of albumin， hemoglobin， lymphocytes， hematocrit， and body mass index at baseline （Z=-3.592， -3.603， -2.602， -3.829， -2.432， all P<0.05）， as well as significantly lower levels of prealbumin， albumin/globulin ratio， apolipoprotein A， and free triiodothyronine at baseline （t=4.530， 3.402， 3.485， and 3.639， all P<0.001）. Compared with the poor response group， the good response group had a significantly lower proportion of patients with liver cirrhosis， gallstones/cholecystitis， or anemia （χ²=20.815， 3.892， and 12.283， all P<0.05）. Baseline RDW （odds ratio ［OR］=1.157， 95% confidence interval ［CI］： 1.028‍ — ‍1.301， P=0.015） and ALP level after one month of treatment （OR=1.012， 95%CI： 1.005‍ — ‍1.020， P=0.002） were independent risk factors for response to UDCA， with an AUC of 0.713 and 0.720， respectively. The patients with baseline RDW≥upper limit of normal （ULN） and ALP≥2.2×ULN after one month of UDCA treatment had a lower UDCA response rate （42.6% vs 8.2%， χ²=20.813， P<0.001）. ConclusionPatients with baseline RDW≥ULN and ALP≥2.2×ULN after one month of UDCA treatment tend to have a low biochemical response rate to UDCA.

Tropane alkaloids (TAs) are a class of anticholinergic drugs widely used in clinical practice and mainly extracted from plant, among which Atopa belladonna is the main commercial drug source. It is of great industrial value to obtain TAs in large quantities by plant metabolic engineering. In TAs pathway, cytochrome oxidase CYP82M3 catalyze the synthesis of tropinone and then tropinone reductase I (TRI) compete with TRII for tropinone to form tropine leading to the TAs synthesis (drainage). In this study, based on the "increasing flow and drainage" metabolic engineering strategy, two genes, namely HnCYP82M3 and DsTRI from Hyoscyamus niger and Datura stramonium, respectively, were overexpressed in the hair roots of A. belladonna, with a view to promote the TAs accumulation. The HnCYP82M3 gene was cloned from the root of H. niger, and it encoded amino acid with 91.7% sequence identity with AbCYP82M3 from A. belladonna. Overexpression of HnCYP82M3 alone did not affect the content of TAs in hair roots of A. belladonna, indicating that CYP82M3 was not a key enzyme in TAs biosynthesis. Simultaneous overexpression of HnCYP82M3 and DsTRI greatly promoted the accumulation of the three TAs, and the contents of hyoscyamine, anisodamine and scopolamine were 4.97 times, 2.83 times and 2.19 times that of the control, respectively, and the increase amplitude was greater than that of single overexpression of DsTRI. This study showed that the "increasing flow and drainage" strategy of enzyme genes co-expression at branch points was a promising metabolic engineering method to effectively improve the biosynthesis of TAs in A. belladonna, and laid a theoretical and technical foundation for the large-scale industrial acquisition of TAs.

Objective To systematically evaluate the risk factors for postoperative delirium after surgery for Stanford type A aortic dissection. Methods We searched the CNKI, SinoMed, Wanfang data, VIP, PubMed, Web of Science, EMbase, The Cochrane Library database from inception to September 2022. Case-control studies, and cohort studies on risk factors for postoperative delirium after surgery for Stanford type A aortic dissection were collected to identify studies about the risk factors for postoperative delirium after surgery for Stanford type A aortic dissection. Quality of the included studies was evaluated by the Newcastle-Ottawa scale (NOS). The meta-analysis was performed by RevMan 5.3 software and Stata 15.0 software. Results A total of 21 studies were included involving 3385 patients. The NOS score was 7-8 points. The results of meta-analysis showed that age (MD=2.58, 95%CI 1.44 to 3.72, P＜0.000 01), male (OR=1.33, 95%CI 1.12 to 1.59, P=0.001), drinking history (OR=1.45, 95%CI 1.04 to 2.04, P=0.03), diabetes history (OR=1.44, 95%CI 1.12 to 1.85, P=0.005), preoperative leukocytes (MD=1.17, 95%CI 0.57 to 1.77), P=0.000 1), operation time (MD=21.82, 95%CI 5.84 to 37.80, P=0.007), deep hypothermic circulatory arrest (DHCA) time (MD=3.02, 95%CI 1.04 to 5.01, P=0.003), aortic occlusion time (MD=8.94, 95%CI 2.91 to 14.97, P=0.004), cardiopulmonary bypass time (MD=13.92, 95%CI 5.92 to 21.91, P=0.0006), ICU stay (MD=2.77, 95%CI 1.55 to 3.99, P＜0.000 01), hospital stay (MD=3.46, 95%CI 2.03 to 4.89, P＜0.0001), APACHEⅡ score (MD=2.76, 95%CI 1.59 to 3.93, P＜0.000 01), ventilation support time (MD=6.10, 95%CI 3.48 to 8.72, P＜0.000 01), hypoxemia (OR=2.32, 95%CI 1.40 to 3.82, P=0.001), the minimum postoperative oxygenation index (MD=−79.52, 95%CI −125.80 to −33.24, P=0.000 8), blood oxygen saturation (MD=−3.50, 95%CI −4.49 to −2.51, P＜0.000 01), postoperative hemoglobin (MD=−6.35, 95%CI −9.21 to −3.50, P＜0.000 1), postoperative blood lactate (MD=0.45, 95%CI 0.15 to 0.75, P=0.004), postoperative electrolyte abnormalities (OR=5.94, 95%CI 3.50 to 10.09, P＜0.000 01), acute kidney injury (OR=1.92, 95%CI 1.34 to 2.75, P=0.000 4) and postoperative body temperature (MD=0.79, 95%CI 0.69 to 0.88, P＜0.000 01) were associated with postoperative delirium after surgery for Stanford type A aortic dissection. Conclusion The current evidence shows that age, male, drinking history, diabetes history, operation time, DHCA time, aortic occlusion time, cardiopulmonary bypass time, ICU stay, hospital stay, APACHEⅡ score, ventilation support time, hypoxemia and postoperative body temperature are risk factors for the postoperative delirium after surgery for Stanford type A aortic dissection. Oxygenation index, oxygen saturation, and hemoglobin number are protective factors for delirium after Stanford type A aortic dissection.

Objective:To study the risk factors of venous thromboembolism(VTE)and the predictive value of the improved VTE score model to identify the risk of VTE in gynecological surgery patients.Methods:From Janu-ary 1,2020 to December 31,2022,41 patients with VTE after gynecological surgery were selected as the VTE group,and a total of 164 patients with adjacent gynecological surgeries during the same period were selected as the non-VTE group with a ratio of 1 :4.Univariate and multivariate Logistic regression analysis were used to ana-lyze the risk factors of VTE after gynecological surgery,and a modified VTE risk factor rapid assessment model(referred to as the improved VTE score model)was constructed.The receiver operating characteristic(ROC)curve was used to study the predictive value for VTE for in gynecological surgery,and compared with the Caprini score model(Caprini table for short).Results:①Multivatiate Logistic regression analysis showed that there were independent risk factors for postoperative VTE in gynecology surgery(OR＞1,P＜0.05),including age≥60 years,BMI≥28 kg/m2,malignant tumors,surgery time＞3 hours,history of thrombosis,and the increased D-di-mer difference before and after surgery.②The Area under Curve(AUC)of ROC was 0.963 in the improved VTE score model with a Youden index 81.10％,sensitivity 87.80％and specificity 93.29％.The AUC of the Caprini score model was 0.888 with Youden index 63.41％,sensitivity 73.17％and specificity 90.24％.The improved VTE score model the Caprini score model identified 92.68％and 85.37％of VTE patients as high-risk or ex-tremely high-risk,respectively,but the difference was not statistically significant(P＜0.05).Conclusions:More attention should be paid to the six independent risk factors for postoperative VTE in gynecology surgery.The two score models showed a similar identified level.However,the improved VTE score model is more simple and easier to operate,has better practicality,and has certain clinical promotion value.

Objective: To investigate the levels of cytidine/uridine monophosphate kinase 2(CMPK2) expression in CD4+T cells of systemic lupus erythematosus(SLE) patients and its correlation with clinical indicators. Additionally, to explore whether CMPK2 can induce pyroptosis in CD4+T cells of SLE patients through NLRP3, potentially providing a new target for the diagnosis and treatment of SLE. Methods: RT-qPCR and Western blot analyses were used to assess the gene and protein expression levels of CMPK2 in SLE CD4+T cells and healthy controls(HC). Pearson or Spearman correlation analysis was performed to evaluate the relationship between CMPK2 mRNA expression levels and clinical indicators. Subsequently, the expression levels of pyroptosis-related proteins, including NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), caspase-1, gasdermin D(GSDMD), and the N-terminal domain of GSDMD(GSDMD-N), were examined in SLE CD4+T cells and HC. Furthermore, the protein expression levels of NLRP3, ASC, caspase-1, GSDMD, and GSDMD-N were detected after silencingCMPK2in SLE CD4+T cells. Results: CMPK2 expression was significantly elevated in SLE CD4+T cells, exhibiting a positive correlation with SLE disease activity index(SLEDAI), anti-dsDNA antibody, anti-nucleosome antibody, anti-C1q antibody, and a negative correlation with complement C3 and C4 levels. Additionally, the expression levels of pyroptosis-related proteins, including NLRP3, ASC, caspase-1, GSDMD, and GSDMD-N significantly increased in SLE CD4+T cells(P<0.05), Moreover, the levels of cytokines IL-1β and IL-18 in the cell culture supernatants were elevated, and there was a notable increase in the rate of cellular pyroptosis(P<0.05). Silencing CMPK2 led to a reduction in the levels of these markers(P<0.05). Conclusion CMPK2 is highly expressed in SLE CD4+T cells and may serve as a diagnostic marker for SLE. Moreover, it is likely involved in the pathogenesis of SLE by promoting CD4+T cell pyroptosis through NLRP3.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Objective To establish a recurrence risk prediction model for meningioma based on HOXA9 DNA methylation.Methods Meningioma-related datasets were downloaded from GEO database for screening homeobox genes(HOXs)with prognostic values using differential methylation and ROC curve analysis and Cox regression analysis.The differentially methylated CpG sites with high predictive efficacy were selected to establish the risk prediction model using Lasso-Cox regression analysis,based on which the patients were divided into high-and low-risk groups by the cutoff value.The methylation levels of CpG sites were verified at the cell and tissue levels using methylation-specific PCR(MS-PCR).Clinical meningioma tissue samples were used to validate the predictive efficacy of the model.Results HOXA9 methylation level was significantly up-regulated in meningiomas(P<0.001)and showed a high diagnostic efficiency(AUC=0.884)as an independent risk factor for overall survival(P<0.01)positively correlated with the degree of malignancy and poor prognosis of meningioma(P<0.05).Risk stratification by HOXA9 methylation was more accurate than WHO grading for predicting recurrence and patient survival time.The AUCs of the sites cg03217995 and cg21001184 were both above 0.8 for meningioma diagnosis and above 0.6 for predicting recurrence.The patients'clinical characteristics differed significantly between the high-and low-risk groups(P<0.001),and the prediction score of the model was an independent prognostic factor for meningioma(P<0.05).MS-PCR results showed that the methylation levels of the two sites increased significantly in meningioma cells.In clinical samples,the combined model showed a high prediction efficiency(AUC=0.857),and the predicted risk of progression was highly consistent with the patients'actual condition.Conclusion High HOXA9 methylation level is a predictor for poor prognosis of meningiomas,and the combined prediction model based on its CpG sites provides a new approach to early screening of meningioma patients at risk of progression.

Objective To explore the mechanism of melatonin(Mel)alleviating cholestatic liver injury in a mouse cholestasis model induced by cholic acid(CA)feeding.Methods A total of 15 8-week-old male C57BL/6J mice were randomly divided into control group,1％CA group,and 1％CA+Mel group,with 5 animals in each group.The control group was fed with normal chow diet,and the other 2 groups were fed with a diet containing 1％CA for 14 d to construct a model of cholestasis,and intraperitoneal injection with 100 mg/kg Mel was given to the mice from the 1％CA+Mel group.Immunohistochemical assay of α-SMA was applied for the liver tissues in the 1％CA group and the 1％CA+Mel group.The mRNA expression levels of fibrosis-related indicators in mouse liver tissue were examined by RT-qPCR.Liquid chromatography tandem mass spectrometry(LC-MS/MS)and automated biochemical analyzer were used to detect the contents of bile acids in the liver tissues and the serum of mouse,respectively.Then real-time qPCR and Western blotting were applied to detect the expression of bile acid synthesis and liver detoxification enzymes related indicators at mRNA and protein levels,respectively,to further investigate the mechanism of bile acid metabolism.Results Compared with the 1％CA group,the mRNA levels of liver fibrosis indicators(such as Tgfβ1,Col Ⅰ a1,Col Ⅱa1 and α-SMA)were significantly reduced(P＜0.05),and activation of stellate cells was obviously weakened displayed by immunohistochemical staining in the 1％CA+Mel group.The 1％CA+Mel group had notably decreased contents of bile acids in the serum and liver tissues,especially taurocholic acid and reduced mRNA levels of cholesterol 7α-hydroxylase(Cyp7a1)and Cyp8b1,while enhanced mRNA levels of hepatic detoxification enzymes Cyp2b10 and udp-glucuronosyltransferase(Ugt1a1)as well as protein levels of Cyp2b10 and sulfotransferase family 2A member 1(Sult2a1/2)when compared with the 1％CA group(P＜0.05).Conclusion Mel exerts its therapeutic effect on cholestasis by decreasing bile acid synthesis and increasing hepatic detoxification enzymes.

By using paddy rice harvested between 2019 and 2023 as the research object,the volatile components of rice grains were detected by headspace solid-phase microextraction coupled with gas chromatography-triple quadrupole mass spectrometry.Qualitative analysis of the compounds was complemented by a standard mass spectrometry database and retention index,while a selected ion monitoring approach was established to quantify the contents of each component through the internal standard method.Multivariate statistical analyses including principal component analysis and orthogonal partial least squares discriminant analysis were employed to identify differential compounds related to freshness of the paddy rice.Subsequently,a classification model for identifying stored paddy rice based on volatile component analysis was developed.A total of 44 kinds of volatile compounds were identified across different harvest years,including aldehydes,alcohols,ketones,acids,esters,phenols and furans.The results of the multivariate statistical analysis revealed that the content-based orthogonal partial least squares discriminant analysis model could effectively distinguish 2023 harvested paddy rice from those harvested between 2019 and 2022 into two distinct categories.Notably,compounds such as hexanoic acid and nonanoic acid along with twelve others were identified as differential compounds based on variable improtance in projection(VIP)values exceeding 1 and p values less than 0.05.The classification model established through volatile component analysis was expected to provide a theoretical foundation for assessing the freshness of stored paddy rice.

Three-dimensional graphene hydrogel(3DGH)was successfully prepared through a hydrothermal method,followed by its composition with gold nanoparticles(AuNPs)to construct a highly sensitive Au/3DGH graphene electrochemical transistor(GECT)dopamine(DA)sensor.AuNPs are efficient electrocatalytic materials.However,their tendency to aggregate during electrodeposition hinds the practical application.The porous and interconnected network structure of 3DGH provided abundant attachment sites,effectively preventing AuNPs aggregation.By modifying the sensor's gate with Au/3DGH,the excellent electrocatalytic performance of Au/3DGH towards DA and the high sensitivity of GECT were utilized to achieve highly sensitive detection of DA.The sensor exhibited a low detection limit of 20 nmol/L and a linear range of 20 nmol/L to 2.5 mmol/L.Remarkably,the sensor showed high sensitivity,excellent selectivity and strong stability,and hold great potnetial in highly sensitive portable detection of DA in disease prevention and clinical monitoring.