ObjectiveTo explore the improving effect of Huangqi Chifengtang（HCT） on atherosclerosis（AS）， and elucidate its mechanism in relation to adenosine monophosphate-activated protein kinase（AMPK）/peroxisome proliferator-activated receptor α（PPARα） signaling pathway and nucleotide-binding oligomerization domain（NOD）-like receptor thermal protein domain associated protein 3（NLRP3） inflammasome. MethodsEight C57BL/6J mice were set as the normal group， and 32 ApoE^-/- mice were randomly divided into the model group， the positive drug group（atorvastatin， 5 mg·kg^-1·d^-1）， HCT low- and high-dose groups（1.95， 3.90 g·kg^-1·d^-1）. ApoE^-/- mice were fed with high-fat and high-cholesterol feed to establish an AS mouse model. After modeling， they were orally administered corresponding dose of drugs for 28 days， while the normal and model groups received an equal volume of physiological saline via oral gavage. Hematoxylin-eosin（HE） staining was used to observe the pathological status of the aorta and liver in mice， Biochemical testing and enzyme-linked immunosorbent assay（ELISA） were used to detect the levels of total cholesterol（TC）， triglycerides（TG）， low-density lipoprotein cholesterol（LDL-C）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， C-reactive protein（CRP）， interleukin（IL）-1β， IL-18 in the serum， as well as superoxide dismutase（SOD）， malondialdehyde（MDA）， and reduced glutathione（GSH） in the liver. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to measure the mRNA expression levels of NLRP3， apoptosis-associated speck-like protein（ASC）， cysteinyl aspartate specific proteinase-1（Caspase-1）， Toll-like receptor 4（TLR4） in the aorta， and fatty acid synthase（FAS）， stearoyl-CoA desaturase 1（SCD1）， PPARα， and carnitine palmitoyltransferase 1A（CPT1A） in the liver. Immunohistochemistry was used to determine the protein expressions of NLRP3， Caspase-1， and ASC in the aorta， and Western blot was used to measure the protein expressions of AMPK， p-AMPK， sterol regulatory element binding protein-1c（SREBP-1c）， CPT1A， and FAS in the liver. ResultsCompared with the normal group， the model group showed a significant increase in lipid plaque deposition in the aorta and lipid accumulation in the liver， the levels of TC， TG， LDL-C， AST， ALT， IL-1β， IL-18 and CRP in the serum were significantly increased（P<0.01）， and the mRNA and protein expressions of aortic TLR4， NLRP3， Caspase-1 and ASC were significantly upregulated（P<0.01）. The levels of SOD and GSH in the liver were significantly reduced， while the level of MDA was significantly increased（P<0.01）. The mRNA expressions of FAS and SCD1 in the liver were significantly downregulated， while the mRNA expressions of PPARα and CPT1A were significantly upregulated. The protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly reduced， while the expressions of SREBP-1c and FAS proteins were significantly increased（P<0.01）. Compared with the model group， the low- and high-dose HCT groups showed significant improvements in aortic plaques and hepatic lipid deposition. The levels of TC， LDL-C， AST， IL-1β and IL-18 in the serum of the low-dose HCT group， as well as TC， TG， LDL-C， AST， ALT， IL-1β， IL-18 and CRP in the serum of the high-dose HCT group， were significantly reduced（P<0.01）. The mRNA expressions of TLR4， NLRP3 and Caspase-1 in the aorta of the low-dose HCT group， as well as TLR4， NLRP3， Caspase-1 and ASC in the aorta of the high-dose HCT group， were significantly downregulated（P<0.01）. The protein expressions of Caspase-1 and ASC in the aorta of the low-dose HCT group， as well as NLRP3， Caspase-1 and ASC in the high-dose HCT group， were significantly downregulated（P<0.01）. The levels of SOD and GSH in the liver of the low- and high-dose HCT groups were significantly increased， while the level of MDA in the high-dose HCT group was significantly decreased（P<0.05， P<0.01）. In the HCT-treated group， the mRNA expressions of FAS and SCD1 in the liver were significantly upregulated， while the mRNA expressions of PPARα and CPT1A were significantly downregulated， the protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly increased， while the protein expressions of SREBP-1c and FAS were significantly decreased（P<0.05， P<0.01）. ConclusionHCT can improve lipid metabolism by activating the AMPK/PPARα pathway and inhibit NLRP3 inflammasome-mediated inflammatory responses， thereby reducing hepatic lipid deposition and AS plaque formation.

ObjectiveTo investigate the intervention effect of Tengli Kangliu prescription （TKP） on the carcinogenesis of colorectal adenoma （CRA） induced by azoxymethane （AOM）/dextran sulphate sodium salt （DSS） in C57BL/6 mice and decipher the potential mechanism through regulating the signal transducer and activator of transcription 3 （STAT3） pathway to target M2-type macrophages. MethodsA total of 55 male C57BL/6 mice were randomized into a blank group （n=10）， a model group （n=15）， a celecoxib （0.02 g·kg^-1·d^-1） group （n=15）， a TKP （42.43 g·kg^-1·d^-1） group （n=15）. The mice in the model， TKP， and celecoxib groups were modeled for CRA lesions through the AOM/DSS three-cycle protocol. The intervention in each group began one week after free access to DSS and lasted for 12 weeks， and the blank group received 20 mL·kg^-1·d^-1 normal saline through gavage. Throughout the study period， changes in body mass and survival rate were recorded， alongside measurements of colorectal length and spleen mass. Histological changes of the colonic tissue were observed by HE staining. Immunohistochemical （IHC） staining was performed to detect the positive expression of CD68 and CD11c in the colorectal tissue. Western blot was employed to assess the protein levels of STAT3， phosphorylated （p）-STAT3， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the intestinal tissue. Real-time quantitative PCR was employed to analyze the mRNA levels of arginase 1 （Arg1）， CD206， and vascular endothelial growth factor （VEGF）. Enzyme-linked Immunosorbent assay（ELISA） was employed to measure the serum concentrations of Th2-type cytokines interleukin （IL）-4， IL-6， and IL-13 in mice. ResultsCompared with the blank group， the model group exhibited symptoms including diarrhea， hematochezia， and body mass loss， accompanied by shortened colon length， mucosal damage， and multiple tumors. In addition， the model group showcased up-regulated protein levels of STAT3， p-STAT3， and Bcl-2， down-regulated protein level of Bax， increased positive expression of CD68 and CD11c， and up-regulated mRNA levels of Arg1， CD206， and VEGF in the colon tissue， together with elevated serum levels of IL-4， IL-13， and IL-6 （P<0.05）. Compared with the model group， the above-mentioned indicators were partially reversed in both TKP group and celecoxib group， with superior effects observed in the TKP group （P<0.05）. ConclusionTKP significantly improves the survival quality of the mouse model of AOM/DSS-induced CRA by reducing intestinal inflammation and decreasing colorectal tumor number and size. It may delay the progression of AOM/DSS-induced colorectal tumor-like lesions by inhibiting activation of the STAT3/p-STAT3 signaling pathway in the intestinal tissue， targeting regulation of M2-type macrophages， and improving the tumor microenvironment， thereby suppressing CRA carcinogenesis.

ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Objective:To synthesize evidence regarding discharge preparation services for patients with severe acute pancreatitis (SAP) .Methods:Systematic search of relevant domestic and international websites and databases for diverse evidence concerning discharge preparation in SAP patients were conducted. Literature quality of the included studies was evaluated, and related evidence was extracted and graded.Results:Based on the researchers' evaluation and synthesis, 25 pieces of evidence related to discharge preparation services for patients with SAP were identified and summarized. These were categorized into five key areas: comprehensive assessment, care planning, multidimensional interventions, post-discharge follow-up, and ongoing evaluation. Among them, the evidence with stronger recommendation levels included multidisciplinary team assessment within 24 hours of admission, the assignment of dedicated personnel to coordinate, monitoring the discharge plan and continuous evaluation of the effectiveness of discharge preparation services.Conclusions:This study summarizes the best evidence available regarding discharge preparation services for SAP patients. It may provide an evidence-based foundation for nursing staff to standardize clinical practice and to further develop discharge preparation programs.

The integration of multi-source data and the establishment of early warning indicator systems constitute pivotal elements for advancing surveillance and early warning capacities in respiratory infectious diseases. Given the multifaceted transmission mechanisms and complex contributing factors inherent in respiratory infectious diseases, surveillance datasets and associated early warning indicators demonstrate notable heterogeneity and sophisticated interrelationships. Furthermore, as surveillance and early warning requirements significantly vary across diverse epidemiological scenarios, accurate assessment of the value and applicability of distinct data types and indicators is imperative. This paper systematically reviews and synthesizes recent advancements in surveillance data and early warning indicators for respiratory infectious diseases, drawing on both domestic and international research. Particular attention is dedicated to analyzing the applicability and efficacy of various data types and indicators within multiple practical contexts, aiming to provide robust theoretical frameworks and methodological guidance to facilitate the development of resilient and efficient surveillance and early warning systems for respiratory infectious diseases.

Objective:To explore the feasibility of joint screening of the two primary immunodeficiency diseases [severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia(XLA)] and spinal muscular atrophy(SMA) in newborns by multiplex real-time quantitative PCR technology, and to provide evidence for early screening, diagnosis and treatment of children.Methods:Cross-sectional study. From July 2021 to January 2023, a total of 103 240 dry blood spots samples of newborns were collected which were delivered to Neonatal Disease Screening Center of Zhejiang by cold chain transportation. The concentrations of the T cell receptor excision ring (TREC), Kappa deletion of the recombinant excision loop (KREC), and exon 7 deletion of Survival Motor Neuron 1 (SMN1) gene in dry blood spots were simultaneously detected by multiplex real-time fluorescence quantitative PCR, taken ribonuclease P/MRP 30 000 subunits (RPP30) as an internal reference gene. The positive newborns were further diagnosed by other laboratory tests and gene sequencing was taken as gold standard. Children samples from 1 case of SCID, 3 cases of XLA and 2 cases of SMA were used for positive verification. The correlation between detected concentration of TREC/KREC and basic information in newborns were analyzed. The differences among groups for each factor were analyzed.Results:One case of SCID, 2 cases of XLA, 9 cases of SMA and 7 cases of other genetic diseases (4 cases of DiGeorge syndrome, 1 case of trisomy 21 syndrome, 1 case of Noonan syndrome and 1 case of super male syndrome) were identified by multiplex real-time fluorescence quantitative PCR. The positive predictive values of screening neonatal SCID, XLA and SMA were 2.44% (1/41), 2.78% (2/72) and 9/9 respectively. Taking the samples from clinically diagnosed 1 case of SCID, 3 cases of XLA and 2 cases of SMA as positive validation samples, which were all identified. The detected results of TREC/KREC correlated with time of blood collection, sex, weight, gestational age and delivery mode of newborns, whose r values were 0.162/0.187, 0.066/0.032, 0.045/0.042, ?0.015/?0.088 and 0.014/0.068 respectively (all P<0.05). Conclusions:Relying on current neonatal screening platform in Zhejiang, it is feasible to screen jointly two kinds of primary immunodeficiency diseases and spinal muscular atrophy in newborns by multiple real-time fluorescence quantitative PCR technology.

Objective To explore the function of electroacupuncture(EA)on body mass,fasting blood glucose,heat pain threshold,and transient receptor potential vanilloid 4(TRPV4)in the dorsal root ganglia(DRG)of rats with diabetic neuropathic pain(DNP).Methods A DNP rat model was formed by intraperitoneally injecting the animals with STZ.From days 15 to 21,bilateral Zusanli and Kunlun points of the DNP rat model were treated with electroacupuncture once daily for 30 min.We then measured their body mass,fasting blood glucose,and heat pain threshold.The co-expression of TRPV4 and NeuN in the rat L4～L6 DRG was detected by immunofluorescence.The effects of the TRPV4 agonist GSK1016790A on body mass,fasting blood glucose,and the heat pain threshold of DNP rats treated with electroacupuncture were detected.Results After the 7th day,body mass was significantly decreased(P<0.01)and fasting glucose was significantly increased(P<0.01)in the model group compared with the normal group.After the 21st day,compared with the model group,heat pain threshold of the model+electroacupuncture group was significantly higher(P<0.01);the results of co-expression of TRPV4 and NeuN immunofluorescence on rat L4～L6 DRG showed that:the expression of positive cells in the model group was significantly higher(P<0.01)than that in the normal group,the co-expression of TRPV4 and NeuN positive cells in L4～L6 DRG of rats in the model+electroacupuncture group was significantly lower(P<0.01)than that in the model group.The TRPV4 agonist GSK1016790A can reverse the downregulation of thermal pain threshold induced by electroacupuncture in DNP rats(P<0.01).Conclusion Electroacupuncture alleviated the DNP induced by STZ,and its mechanism may involve the inhibition of TRPV4 protein expression in the DRG.

Post-acute pancreatitis diabetes mellitus (PPDM-A) is a common type of exocrine pancreatic diabetes. It is very important to clarify the risk factors of PPDM-A and effectively screen for diabetes in patients with acute pancreatitis to prevent the occurrence and development of PPDM-A. This article elaborates on the three aspects of PPDM-A, including high-risk population, screening timing and methods, as well as PPDM-A screening in children and adolescents, aiming to provide a basis for early detection of PPDM-A and timely targeted treatment for patients.

OBJECTIVE To explore the effects of Tianma xiongling zhixuan tablet on autophagy in vascular endothelial cells of rats and its potential mechanism. METHODS The rat aortic endothelial cells （RAECs） were divided into normal group， model group， blank serum group， traditional Chinese medicine （TCM） medicated serum group， autophagy blocker group， autophagy agonist group， and TCM combined with autophagy agonist group. Except for normal group， other groups were given 10 μg/mL lipopolysaccharide for 24 hours to induce RAECs inflammation injury model. Blank serum group was treated with 10% blank serum； TCM medicated serum group received 10% medicated serum derived from Tianma xiongling zhixuan tablet； autophagy blocker group was treated with 20 μmol/L of PD98059； autophagy agonist group was administered 50 μmol/L Honokiol. Lastly， the TCM combined with autophagy agonist group was given both 10% medicated serum derived from Tianma xiongling zhixuan tablet and 50 μmol/L Honokiol. The morphological characteristics of RAECs in each group were observed. The cell viability of each group， the contents of endothelin-1 （ET-1） and nitric oxide （NO）， mitochondrial reactive oxygen species， mitochondrial membrane potential， and the expression levels of PTEN-induced kinase 1 （PINK1）， Parkin， ubiquitin-binding protein （p62）， and microtubule-associated protein 1 light chain 3 （LC3） were detected. RESULTS Compared with model group， the levels of ET-1， mitochondrial reactive oxygen species， and the relative expressions of PINK1， Parkin， and LC3 proteins in the autophagy blocker group and TCM medicated serum group were decreased or down-regulated significantly （P＜0.05 or P＜0.01）； the cell viability rate （only autophagy blocker group）， NO level， mitochondrial membrane potential， and the E-mail：46164660@qq.com relative expression level of p62 protein were increased or up-regulated significantly （P＜0.05 or P＜0.01）； the pathological damage of RAECs was significantly improved， the number of cells increased significantly， and the typical paving stone-like characteristics were restored. The levels of ET-1， mitochondrial reactive oxygen species， and the relative expression levels of Parkin and LC3 proteins in the autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while cell viability rate was decreased significantly （P＜0.05）， the damage of RAECs was aggravated. Compared with the autophagy agonist group， the cell viability rate and the relative expression level of p62 protein in TCM combined autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while the levels of ET-1， the relative expression levels of PINK1， Parkin， and LC3 proteins were down-regulated significantly （P＜ 0.01）， the damage of RAECs was reversed to a certain extent. CONCLUSIONS Tianma xiongling zhixuan tablet protects vascular endothelial function by regulating mitochondrial autophagy， the mechanism of which may be associated with the regulation of PINK1/Parkin signaling pathway and the inhibition of mitochondrial autophagy.