ObjectiveTo study the clinical characteristics and influencing factors of rheumatoid arthritis （RA） in the patients with cold dampness obstruction syndrome. MethodsThe RA patients treated in the Department of Traditional Chinese Medicine and Rheumatology of the China-Japan Friendship Hospital from August 2022 to June 2024 were selected. The demographic information， clinical data， laboratory test results， and traditional Chinese medicine （TCM） symptom information were collected for syndrome differentiation， on the basis of which the characteristics and influencing factors of cold dampness obstruction syndrome were analyzed. ResultsA total of 258 RA patients were selected in this study， including 88 （34.1%） patients with cold dampness obstruction syndrome， 53 （20.5%） patients with dampness and heat obstruction syndrome， 31 （12.0%） patients with wind dampness obstruction syndrome， 29 （11.2%） patients with liver-kidney deficiency syndrome， 19 （7.4%） patients with Qi-blood deficiency syndrome， 14 （5.4%） patients with phlegm-stasis obstruction syndrome， 15 （5.8%） patients with stasis obstructing collateral syndrome and 9 （3.5%） patients with Qi-Yin deficiency syndrome. The patients were assigned into two groups of cold dampness obstruction syndrome and other syndromes. The group of cold dampness obstruction syndrome had lower joint fever， 28-tender joint count （TJC28）， and 28-joint disease activity score （DAS28）-C-reactive protein （CRP） and higher central sensitization， cold feeling of joints， fear of wind and cold， cold limbs， and abdominal distention than the group of other syndromes （P<0.05）. The binary logistic regression analysis showed that central sensitization （OR 5.749， 95%CI 2.116-15.616， P<0.001） and DAS28-CRP （OR 0.600， 95% CI 0.418-0.862， P=0.006） were the independent factors influencing cold dampness obstruction syndrome in RA. ConclusionCold dampness obstruction syndrome is a common syndrome in RA patients. It is associated with central sensitization， cold feeling of joints， abdominal distension and may be a clinical syndrome associated with central sensitization.

BACKGROUND:The regulation of intestinal flora by exercise is closely related to human health,but intestinal flora involves many factors.Existing studies have lacked consistent evidence on the effect of exercise on the intestinal flora of college students. OBJECTIVE:To explore the effects of exercise on intestinal flora diversity and species composition of college students. METHODS:Through systematic search of PubMed,Web of Science,Embase,Medline,Cochrane Library,CNKI,WanFang Database and VIP database,eight empirical studies were selected and included,and semi-quantitative analysis was performed on them. RESULTS AND CONCLUSION:In terms of the species diversity of the intestinal flora,both high-intensity interval training and Tai Chi exercise significantly enhance the species diversity of intestinal flora in college students,while aerobic exercise does not have a significant effect on the enhancement of intestinal flora diversity in college students.In terms of the species composition of the intestinal flora,all three exercise modalities significantly alter the compositional structure of the intestinal flora in college students,which can increase the abundance of beneficial bacteria such as Ruminalococcus,Faecalis prevotelli,Blautia,and decrease the abundance of harmful bacteria such as Escherichia spp.Compared with high-intensity interval training,aerobic and Tai Chi exercise causes more elevated abundance of beneficial bacteria.In addition to changes in intestinal flora characteristics,exercise improves body composition,cardiorespiratory function,and executive function in college students,and these health benefits are closely linked to exercise-induced changes in intestinal flora that can produce health benefits for the body through metabolic regulation,barrier function,and neuromodulation.Although studies have confirmed the association between exercise and intestinal flora,the mechanism by which exercise affects intestinal flora has not yet been clarified,and at the same time,localizing the flora related to the host health is the key to targeting intestinal flora as a therapeutic target in the future,all of which are worthy of further attention and investigation.

ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

Objective To investigate the effect of 1,25(OH)2 D3-mediated vitamin D receptor(VDR)expression on oxidative stress injury in nucleus pulposus cells.Methods Human interdisc nucleus pulpocytes were randomly divided into control group,H2O2 group(400 μmol·L-1H2O2),1,25(OH)2 D3 group[100.00 nmol·L-11,25(OH)2D3+400 μmol·L-1H2O2],1,25(OH)2D3+si-NC group[100.00 nmol·L-1 1,25(OH)2D3+400 μmol·L-1 H2O2+si-NC],1,25(OH)2D3+si-VDR group[100.00 nmol·L-1 1,25(OH)2D3+400 μmol·L-1 H2O2+si-VDR].Cell survival rate was measured by methyl thiazolyl tetrazolium(MTT)assay.Western blot assay was used to detect the protein expression level of each group.Apoptosis,mitochondrial membrane potential and reactive oxygen species(ROS)levels were detected by flow cytometry,JC-1 fluorescence probe and DCFH-DA probe,respectively.Malonclialdehyde(MDA)and superoxide dismutase(SOD)levels were detected with the kit.Results The cell survival rates of control group,H2O2 group,1,25(OH)2D3 group,1,25(OH)2D3+si-NC group and 1,25(OH)2D3+si-VDR group were(100.00±2.43)％,(63.79±5.21)％,(90.11±7.24)％,(88.79±6.48)％and(55.31±4.65)％;VDR protein levels were 0.79±0.06,0.28±0.03,0.68±0.05,0.69±0.06 and 0.34±0.04;the apoptosis rates were(4.12±0.26)％,(19.37±1.21)％,(8.49±0.57)％,(8.23±0.60)％and(14.68±1.37)％;mitochondrial membrane potential levels were(100.00±4.31)％,(49.46±5.02)％,(82.14±7.02)％,(83.14±5.12)％and(67.16±5.48)％;ROS levels were 1.79±0.12,7.98±0.51,3.87±0.34,3.92±0.22 and 5.79±0.28;Beclin-1 levels were 0.86±0.09,0.35±0.04,0.76±0.07,0.75±0.08 and 0.46±0.05;LC3-Ⅱ/LC3Ⅰ levels were 1.00±0.07,0.25±0.04,0.78±0.07,0.85±0.08 and 0.42±0.05,respectively.Compared H2 O2 group with control group,compared 1,25(OH)2 D3 group with H2O2 group,compared 1,25(OH)2D3+si-VDR group with 1,25(OH)2D3+si-NC group,the differences of the above indicators were all statistically significant(all P＜0.05).Conclusion 1,25(OH)2 D3 may up-regulate the expression of VDR,promote autophagy and inhibit apoptosis of nucleus pulposus cells,and play an anti-oxidative stress role.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Objective: To explore the moderating role of estradiol in the relationship between parenting styles and preschool children's behavioral problems, so as to provide a theoretical basis for improving the development of human s emotional health development in early life stage. Methods: During September to November in 2022, 354 children aged 3-6 years and their parents from two kindergartens in Bengbu City were chosen by using stratified cluster sampling method for the questionnaire survey. The Parenting Style Scale and the Child Behavior Checklist (CBCL) were used to collect information on parenting style and child behavioral problems. Salivary estradiol of children was collected and tested. Independent samples t test was applied to compare the scores of the scale for parental up bringing and children s behavioral problems, and Pearson correlation analysis was conducted to explore the relationship among parental upbringing, estradiol and children s behavioral problems. Results: Parents doting, laissez faire, autocratic, and inconsistent parenting styles were positive associated with child behavior problems( r =0.14-0.70); fathers democratic parenting style was negatively associated with child behavior problems( r =-0.14，-0.22，-0.21，-0.17，-0.27，-0.20); mothers democratic parenting styles was negatively correlated with scores on all five dimensions of child behavior problems except the withdrawal dimension ( r =-0.14，-0.12，-0.13，-0.21，-0.12)( P <0.05). Estradiol levels had significant moderating effects on maternal doting parenting style and children s withdrawal ( β =0.68) as well as social problems ( β =-1.00), also moderating laissez faire parenting styles and children s withdrawal problems ( β =0.75)( P <0.05). For children with low levels of estradiol, withdrawal problem scores were negatively associated with mother s doting parenting style and positively associated with laissez faire parenting style, and socialization problem scores were associated with mother s doting parenting style; for children with high levels of estradiol, withdrawal problem scores were positively associated with mother s doting parenting style, and socialization problem scores were associated with mother s doting parenting style ( t=2.84, 6.24, 3.16 , 2.37, 4.49, P <0.05). Conclusions Parenting styles are strongly associated with child behavioral problems; estradiol levels play a moderating role in mothers doting, laissez faire parenting styles and children s withdrawal problems and social problems.Parents should adopt more positive parenting styles and focus on the role of estradiol levels in maternal education to reduce the occurrence of behavioral problems in children.

Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT₇ receptor protein expression in the cells, indicating potential antidepressant activity.

OBJECTIVE To establish a quantitative analysis model for the contents of tussilagone， moisture， ethanol-soluble extract and total ash in Farfarae Flos based on near-infrared spectroscopy （NIRS）， providing a new idea for the rapid quality evaluation of Farfarae Flos and its preparations. METHODS Referring to the 2020 edition of the Chinese Pharmacopoeia， the contents of the main quality control indexes tussilagone， moisture， ethanol-soluble extract and total ash in 130 batches of Farfarae Flos from 19 producing areas were determined by HPLC， drying method， hot dip method and ash assay， respectively. The NIRS data information of the medicinal herbs of Farfarae Flos was collected， and then NIRS combined with the partial least squares method was used to establish the individual quantitative analysis models of the above quality control indexes in the samples， and the predictive model of the NIRS content was obtained after sample validation with validation set. RESULTS The range for the contents of tussilagone， moisture， ethanol-soluble extract and total ash in 130 batches of Farfarae Flos were 0.051 4%-0.103 5%， 7.75%-10.93%， 20.17%-31.12%， and 7.68%-12.10%， respectively. The internal cross-validation coefficients of determination （R2） of the established models for the quantitative analysis of tussilagone， moisture， ethanol-soluble extract and total ash in Farfarae Flos were 0.985 8， 0.968 4， 0.973 4， 0.988 0， respectively； the root mean square errors of calibration （RMSEC） were 0.001 54， 0.187， 0.478， 0.127， respectively； the root mean square errors of prediction （RMSEP） were 0.001 81， 0.212， 0.543， 0.149， respectively； RMSEP/RMSEC were 1.175 3， 1.133 7， 1.136 0 and 1.173 2， respectively， which were all within a reasonable range （1＜RMSEP/RMSEC≤1.2）. The mean absolute errors between the true and model-predicted values of the above four quality control indexes in the validation set of samples were －0.000 36， 0.061 43， 0.144 00， and 0.010 43， respectively，and the mean predicted recoveries were 99.65%， 100.72%，100.66%， and 100.15%， respectively. CONCLUSIONS The established NIRS quantitative analysis model has high stability and reliable results， which can be used for the rapid batch prediction of the content of relevant quality control indexes in Farfarae Flos.

Objective:To discuss the effect of ligustilide on the cardiac function and angiogenesis in the rats with heart failure,and to clarify its regulatory effect on protein kinase D1(PKD1)/hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)pathway.Methods:The SD rats were randomly divided into sham operation group,model group,ligustilide group,PKD1/HIF-1α/VEGF signaling pathway inhibitor CID755673(CID)group,and ligustilide+CID group.The heart failure rat model was established by ligation of the left anterior descending coronary artery.The rats in ligustilide group were injected intravenously with 20 mg·kg-1 ligustilide,the rats in CID group were injected intraperitoneally with 50 mg·kg-1 CID,and the rats in ligustilide+CID group were injected intraperitoneally with 50 mg·kg-1 CID followed by intravenous injection of 20 mg·kg-1 ligustilide,once per day for 4 consecutive weeks.The cardiac function indexes of the rats in various groups were detected by echocardiography;the percentages of myocardial infarction areas of the rats in various groups were detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining;the pathomorphology of myocardium tissue of the rats in various groups was observed by HE staining;the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in ischemic area of myocardium tissue of the rats in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.Results:Compared with sham operation group,the rats in model group and CID group had altered myocardial cell morphology,increased intercellular gaps,disorganized arrangement,visible muscle fiber breaks and inflammatory cell infiltration;the rats in ligustilide group and ligustilide+CID group had relatively orderly myocardial fiber arrangement,fewer myocardial fiber breaks and decreased number of inflammatory cells.Compared with sham operation group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)of the rats in model group were decreased(P<0.05),the left ventricular end-systolic diameter(LVESD)and left ventricular end-diastolic diameter(LVEDD)were increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05).Compared with model group,the LVEF and LVFS of the rats in ligustilide group were increased(P<0.05),the LVESD and LVEDD were decreased(P<0.05),the percentage of myocardium infarction area was decreased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were increased(P<0.05);compared with model group,the LVEF and LVFS of the rats in CID group were decreased(P<0.05),the LVESD and LVEDD were increased(P<0.05),the percentage of myocardium infarction area was increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05);compared with ligustilide group,the LVEF and LVFS of the rats in ligustilide+CID group were decreased(P<0.05),the LVESD and LVEDD were increased(P<0.05),the percentage of myocardium infarction area was increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05);compared with CID group,the LVEF and LVFS of the rats in ligustilide+CID group were increased(P<0.05),the LVESD and LVEDD were decreased(P<0.05),the percentage of myocardium infarction area was decreased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were increased(P<0.05).Conclusion:Ligustilide can promote the angiogenesis,reduce the myocardium infarction area,and improve the cardiac function in the rats with heart failure;it works through activation of the PKD1/HIF-1α/VEGF pathway.