ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.

Objective We aimed to investigate the hemostatic effect and mechanism of modified Sijunzi Decoction(MSJZT),consisting of tangshen,India bread,largehead atractylodes rhizome,liquorice root,milkvetch root,ass hide glue,and India madder root,on the zebrafish intestinal bleeding model through 5-hydroxytryptamine(5-HT)and its receptors(5-HT2aR,5-HT2bR).Methods Zebrafish at 4 days post fertilization were used as the research object.An intestinal bleeding model was established by induction with 6 μmol/L simvastatin for 24 hours.The zebrafish were divided into normal group,model group,MSJZT low-,mid-and high-concentration groups(55.6,167,500 mg/L),and after modeling,the corresponding concentration of MSJZT was administered.The samples were collected after 24 hours.Platelet count(PLT)and bleeding status were observed.The content of 5-HT and Caspase 3/7 activity were detected by colorimetry.The gene expressions of 5-HT2aR,5-HT2bR and serotonin transporter(SERT)were detected by real-time PCR.The protein expressions of protein kinase B(AKT),phosphorylated AKT(p-AKT),extracellular signal-regulated protein kinase(ERK),and phosphorylated ERK(p-ERK)were detected by Western blotting.Results The intestinal bleeding rate in the model group was 70.0%,and that in the MSJZT low-,mid-and high-concentration groups was 36.7%,40.0%,and 80.0%,respectively;the intestinal hemostatic effect was 54%,52%,and 7%,respectively.Compared with the model group,the PLT in the MSJZT low-and mid-concentration groups decreased;the content of 5-HT in all MSJZT groups increased,and the gene expressions of 5-HT2aR and 5-HT2bR were up-regulated.The gene expression of SERT was up-regulated in the low-and mid-concentration groups;the Caspase 3/7 activity in the mid-and high-concentration groups was reduced;the expressions of p-AKT and p-ERK proteins were up-regulated in the low-and mid-concentration groups(all P<0.05).Conclusion MSJZT can reduce the incidence and severity of intestinal bleeding in zebrafish intestinal bleeding models.The mechanism may be achieved by activating AKT and ERK signaling pathways through 5-HT and its receptors.

Rapid epidemiological screening for tuberculosis (TB) usually uses tuberculin pure protein derivative (PPD) skin test, which has limitations such as low specificity and high side effects. ESAT-6 and CFP-10 are secreted proteins of Mycobacterium tuberculosis, but the related genes are missing from Bacillus Calmette-Guerin (BCG). In this study, the fusion protein ESAT6-CFP10 (EC) was expressed and purified, and prepared into chitosan nanoparticles (EC-NPs), which were loaded into the microneedle patch and carried out the preliminary test of tuberculosis skin test. The drug loading capacity of MNP-EC-NPs (microneedle patch, MNP) can reach 0.03 μg per needle and 1.92 μg per patch. The shelf life of MNP-EC-NPs can reach 6 months at room temperature, and it can effectively penetrate the epidermis. Volunteer skin test results showed that MNP-EC-NPs can effectively distinguish between BCG vaccinators, and can effectively show positive reaction in the skin of tuberculosis patients without significant side effects. The experiment was approved by the Ethics Committee of Wuhan Pulmonary Hospital [2022 (2)]. In this study, a TB skin test method was established, using ESAT6-CFP10 fusion protein instead of PPD, and using soluble microneedle dosage form, which improved the specificity of TB skin test diagnosis and provided a new technical scheme for TB epidemic screening.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

Fluorescent surgical navigation has been widely used in liver and biliary surgery, including imaging of tumors, bile ducts, blood vessels, and other small lesions that cannot be identified by traditional methods. This helps surgeons obtain visual information during surgery and facilitates intraoperative decision-making. However, there are still many controversies in pancreatic tumor surgery, which is also the reason for the limited application of this technology in the pancreas at present. This article first summarizes the current status of the application of this technology in pancreatic tumor surgery. Based on our own experiences, we summarize the current problems of fluorescence imaging technology and propose corresponding optimization strategies. Finally, we look forward to its application prospects, hoping to provide a reference for the future application of fluorescence imaging technology in pancreatic tumors.

Objective:Non-alcoholic fatty liver disease(NAFLD)has significant genetic susceptibility.Adipocytokines play a crucial role in NAFLD development by participating in insulin resistance and hepatic steatosis.However,the association between adipocytokine pathway genes and NAFLD remains unclear.This study aims to explore the association of gene polymorphisms in the adipocytokine pathway and their interactions with NAFLD in obese children. Methods:A case-control study was conducted,dividing obese children into NAFLD and control groups.Peripheral venous blood(2 mL)was collected from each participant for DNA extraction.A total of 14 single nucleotide polymorphisms(SNP)in the adipocytokine pathway were genotyped using multiplex PCR and high-throughput sequencing.Univariate and multivariate Logistic regression analyses were used to assess the association between SNP and NAFLD in obese children.Dominant models were used to analyze additive and multiplicative interactions via crossover analysis and Logistic regression.Generalized multifactor dimensionality reduction(GMDR)was used to detect gene-gene interactions among the 14 SNPs and their association with NAFLD in obese children. Results:A total of 1 022 children were included,with 511 in the NAFLD group and 511 in the control group.After adjusting for age,gender,and BMI,multivariate Logistic regression showed that PPARG rs1801282 was associated with NAFLD in the obese children in 3 genetic models:heterozygote model(CG vs CC,OR=0.58,95%CI 0.36 to 0.95,P=0.029),dominant model(GG+CG vs CC,OR=0.62,95%CI 0.38 to 1.00,P=0.049),and overdominant model(CC+GG vs CG,OR=1.72,95%CI 1.06 to 2.80,P=0.028).PRKAG2 rs12703159 was associated with NAFLD in 4 genetic models:heterozygous model(CT vs CC,OR=1.51,95%CI 1.10 to 2.07,P=0.011),dominant model(CT+TT vs CC,OR=1.50,95%CI 1.10 to 2.03,P=0.010),overdominant model(CC+TT vs CT,OR=0.67,95%CI 0.49 to 0.92,P=0.012),and additive model(CC vs CT vs TT,OR=1.40,95%CI 1.07 to 1.83,P=0.015).No significant multiplicative or additive interaction between PPARG rs1801282 and PRKAG2 rs12703159 was found in association with NAFLD.GMDR analysis,adjusted for age,gender,and BMI,revealed no statistically significant interactions among the 14 SNPs(all P>0.05). Conclusion:Mutations in PPARG rs1801282 and PRKAG2 rs12703159 are associated with NAFLD in obese children.However,no gene-gene interactions among the SNP are found to be associated with NAFLD in obese children.

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.