ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by oral and periocular dryness. Astragalus-Salvia (AS) and Ophiopogon-Dendrobium (OD) represent two frequently utilized herb pairs in SS treatment. While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms, its underlying mechanism remains unclear. This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic (NOD)/Ltj mice with SS. The study utilized NOD/Ltj mice as SS models, administering AS-OD treatment for 10 weeks at doses of 113.1, 226.2, and 339.3 mg·d^-1·20 g^-1. Results demonstrated that AS-OD improved SS symptoms, evidenced by enhanced salivary flow rate, decreased anti-SSA/Ro and anti-SSB/La antibody levels, increased swimming duration, and reduced lactate (LA) and blood urea nitrogen (BUN) levels in NOD/Ltj mice. AS-OD reduced lymphocyte infiltration, enhanced Aquaporin-5 (AQP5) expression in the submandibular gland, decreased inflammatory cytokine levels in the submandibular gland, and reduced the T helper type 17/regulatory T lymphocyte (Th17/Treg) cell ratio in the spleen. Transcriptomic and proteomic analyses indicated AS-OD's involvement in regulating phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and Janus kinase 3/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways, with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells. Furthermore, AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway. In A-253 cells, AS-OD reduced inflammatory cytokine levels, CXC chemokine ligand 9/10 (CXCL9/10), and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway. AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Sjogren's Syndrome/immunology* ; Mice, Inbred NOD ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Janus Kinase 1/genetics* ; Humans ; Female ; Astragalus Plant/chemistry* ; Male

Objective To explore the relationship between serum CXC chemokine ligand 12(CXCL12),an-giotensin Ⅱ receptor-like 1 endogenous ligand 13(Apelin-13)and carotid atherosclerosis(CAS)in patients with type 2 diabetes mellitus(T2DM).Methods From October 2022 to September 2024,a total of 105 T2DM patients in Rugao People's Hospital(the hospital)were included as the T2DM group,and healthy volunteers who experienced physical check ups in the hospital were regarded as the control group.According to whether T2DM patients developed CAS,they were assigned into non CAS group(n=61)and CAS group(n=44).Fully automatic biochemical analyzer was applied to detect the levels of blood lipid indicators total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein choles-terol(LDL-C).Fully automatic glycated hemoglobin analyzer was used to detect glycated hemoglobin(HbA1c)level.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of CXCL12 and Apelin-13.Multivariate Logistic regression was applied to analyze the influencing factors of concurrent CAS in T2DM.Pearson correlation was used to analyze the correlation between CXCL12,Apelin-13 and the course of diabetes,blood glucose and lipid indicators.Receiver operating characteristic(ROC)curve was applied to ana-lyze the predictive value of CXCL12 and Apelin-13 for T2DM complicated with CAS,and the Z-test was ap-plied to compare the differences in the area under the curve(AUC).Results The level of CXCL12 in the T2DM group was higher than that in the control group(P＜0.05),and Apelin-13 level was lower than that in the control group(P＜0.05).The course of T2DM,HbA1c,TC,TG,LDL-C,and CXCL12 levels in the CAS group were higher than those in the non CAS group(P＜0.05),while HDLC and Apelin-13 levels were lower than those in the non CAS group(P＜0.05).The level of CXCL12 in the CAS group was positively correlated with the course of T2DM,HbA1c,TC,TG,and LDL-C levels(P＜0.05),and negatively correlated with HDL-C levels(P＜0.05),while the correlation of Apelin-13 was opposite(P＜0.05).CXCL12 and Apelin-13 were independent influencing factors for concurrent CAS in T2DM patients(P＜0.05).The AUC predicted by CX-CL12 and Apelin-13 in T2DM patients complicated with CAS was 0.916,which was better than 0.783 and 0.788 predicted separately(P＜0.05).Conclusion The high levels of CXCL12 and low levels of Apelin-13 in the serum of T2DM patients are independent influencing factors for concurrent CAS in T2DM.The combined detection of CXCL12 and Apelin-13 to predict CAS in T2DM patients has certain clinical significance and pro-vides a basis for disease assessment and treatment.

Objective:To evaluate the dynamic changes in fibrinolytic states after initial resuscitation in severe trauma patients, and to analyze the relationship between the changes and clinical outcomes.Methods:A prospective cohort study was conducted on severe trauma patients admitted to the trauma center in Taicang Hospital, affiliated with Soochow University, from July 2021 to December 2022. Resuscitation treatments, including tranexamic acid (TXA), were administered. Thromboelastography was performed at three intervals: upon admission, 1 hour and 8 hours after initial resuscitation. Fibrinolytic states were categorized into three phenotypes based on clot lysis at 30 minutes: fibrinolysis shutdown (SD), physiologic fibrinolysis (PY), and hyperfibrinolysis (HF). The primary outcomes included all-cause mortality at 24 hours and 28 days. Multivariate logistic regression was used to analyze the association between early fibrinolytic changes and clinical outcomes.Results:A total of 132 patients with severe trauma were included. Upon admission, fibrinolytic phenotypes were distributed as follows: SD in 61 patients (46.2%), PY in 59 patients (44.7%), and HF in 12 patients (9.1%). After resuscitation with TXA and other interventions, SD and PY remained predominant, whereas HF further decreased. Compared with the SD and PY groups, the HF group had significantly higher 24-hour mortality (25.0% vs. 3.3% vs. 3.4%, P<0.05) and 28-day mortality (58.3% vs. 32.8% vs. 11.9%, P<0.05), with massive hemorrhage being the primary cause of death. Among the non-HF groups, 28-day mortality was significantly higher in the SD group than in the PY group (32.8% vs. 11.9%, P<0.05), with traumatic brain injury as the leading cause of death. After the exclusion of 12 HF patients, multivariate logistic regression showed that after adjusting for age, Glasgow Coma Scale score ≤ 8, prothrombin time, and 24-hour crystalloid infusion volume, identified persistent SD was a risk factor for 28-day mortality in severe trauma patients, compared with sustained PY status ( OR=7.009, 95% CI: 1.141-43.079, P=0.036). Conclusions:In patients with severe trauma, SD and PY are the predominant fibrinolysis phenotypes after initial and early resuscitation. Persistent SD following resuscitation is significantly associated with an increased risk of 28-day mortality.

AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

With the rapid growth of metabolic dysfunction （MD） worldwide， there is also a gradual increase in the number of patients with chronic hepatitis B virus （HBV） infection and MD. Comorbidity with metabolic disorders such as hyperglycemia， hypertension， and dyslipidemia may increase the risk of adverse liver outcomes and cardiovascular events in patients with chronic HBV infection and affect the response to anti-HBV therapy. The standardized management of patients with chronic HBV infection and MD has become a challenge at present， and further in-depth research on the interaction between MD and HBV and targeted management strategies will help to optimize the clinical management of patients with chronic HBV infection.

Foot bath technique is booming in daily health care services. In order to develop a more standardized and complete technical operation process, the working group recorded the whole process of document formulation while writing the Technical Operation Specification for TCM Health Care Services (Non-Medical) Foot Bath (2024 edition). Work profile (including task background, task source, drafting unit, participant grouping and responsibilities), main technical content (including the basis and principles of preparation, key technical content of technical specifications), main preparation process (formation of working groups, registration and plan writing, selection and determination of clinical issues, literature research, drafting of the first draft, consensus on the main content of technical specifications, soliciting opinions, testing applications and external review), the relationship of current mandatory national standards or policies and regulations, the treatment process and basis of major differences, publicity and implementation and post-effect evaluation, the proposal to abolish the current relevant guidelines and the corresponding annexes were under detailed and in-depth description, which can assist the relevant practitioners of non-medical institutions to better understand and apply this technical specification.

This article explored the treatment of laryngopharyngeal reflux disease （LPRD） from the perspective of ascending and descending of qi. It is believed that the disorder of qi movement of the middle jiao （焦） is the key to the pathogenesis of LPRD. The ascending and descending disorder of liver and lung is an important factor in its prolongation and progression. The treatment of LPRD should follow the nature of the spleen and stomach， with the focus on fortifying and transporting the spleen and the stomach， supplemented by soothing the liver and diffusing the lung. The herbs such as Cangzhu （Rhizoma Atractylodis）， Fuling （Poria）， Yiyiren （Semen Coicis）， Gegen （Radix Puerariae Lobatae） and Shanyao （Rhizoma Dioscoreae） could be used for fortifying and circuiting the center earth， and Chaihu （Radix Bupleuri）， Muxiang （Radix Aucklandiae）， Zhiqiao （Fructus Aurantii） and Baishao （Radix Paeoniae Alba） for soothing the liver and nourishing the blood to harmonize the ascending and descending. Jiegeng （Radix Platycodonis） and Xuanfuhua （Japanese Inula Flower） are supplemented to diffuse and direct lung qi downward thereby mediating the center jiao. In this way， the qi movement of the spleen and stomach is restored， and the ascending and descending between the liver and lung are harmonized， and therefore the disease is cureda.

ObjectiveTo investigate the mechanism of Magnolia officinalis cortex for constipation-type irritable bowel syndrome（IBS-C） rats before and after sweating. MethodIBS-C rat model was established by gavage of ice water， and rats were randomly divided into the blank group， model group， mosapride group（1 mg·kg^-1）， M. officinalis cortex group（10 g·kg^-1） and sweated M. officinalis cortex group（10 g·kg^-1）. The changes of body weight， fecal number and fecal water content of rats were observed， 16S rRNA sequencing was used to detect the structural changes of fecal intestinal flora in rats， the levels of 5-hydroxytryptamine（5-HT） and substance P（SP） in colonic tissues of rats were determined by enzyme-linked immunosorbent assay（ELISA）. ResultCompared with the model group， the fecal water content and fecal number of mosapride group， M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased（P<0.05）. At the phylum level， the top four species of flora abundance were Firmicutes， Bacteroidetes， Spirochaetes and Proteobacteria. Compared with the blank group， the proportion of Firmicutes in the model group was significantly reduced（P<0.05）， while the proportion of Spirochaetes was significantly increased（P<0.05）. Compared with the model group， the proportion of Firmicutes and Spirochaetes in M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to that in the blank group， and the proportion of Spirochaetes in sweated M. officinalis cortex group was lower than that of M. officinalis cortex group. At the family level， the top four species of flora abundance were Lactobacillaceae， S24_7， Ruminococcaceae， Bacteroidaceae， compared with the blank group， the proportion of Lactobacillaceae in the model group decreased significantly（P<0.05）， and its proportion in the M. officinalis cortex group and sweated M. officinalis cortex group increased significantly after administration（P<0.05）， and the flora structure of the two groups tended to be similar to that of the blank group. At the genus level， the top four species of flora abundance were Lactobacillus， Unspecified_S24_7， Bacteroides and Treponema. Compared with the blank group， the proportion of Lactobacillus in the model group decreased significantly（P<0.05）， while the proportion of Treponema increased significantly（P<0.05）. Compared with the model group， ratio of bacterial structure of Lactobacillus and Treponema in the M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to those in the blank group， indicating that M. officinalis cortex could restore the intestinal microbial structure of IBS-C rats before and after sweating. Compared with the model group， the 5-HT content in mosapride group was significantly reduced（P<0.05）， the contents of 5-HT and SP in the M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased（P<0.01）， and the sweated M. officinalis cortex group was higher than the M. officinalis cortex group. ConclusionM. officinalis cortex can play a therapeutic role on IBS-C rats by regulating 5-HT pathway and intestinal flora structure before and after sweating.