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.

Objective To analyze the trend of influenza epidemic intensity in Urumqi City, Xinjiang, in early 2023, and to provide a reference basis for influenza surveillance, prevention and control. Methods Based on the daily number of influenza cases in Urumqi from January 1, 2023 to March 26, 2023, a generalized linear model was established to correlate the cumulative number of cases with the number of days of illness, and the corresponding doubling time was calculated. Results A total of 9 243 influenza cases were included in this study, including 7733 confirmed cases and 1510 suspected cases. The peak incidence of influenza occurred in March, and 6039 positive cases were detected, with a positivity rate of 78.09%. The age group of 3-6 years old had the highest proportion of influenza positive cases, accounting for 32.20%. The longest doubling time among confirmed cases was 13.49 (95% CI:11.95-15.47) in stage 2 (January 22 to February 13), and the shortest was in stage 3 (February 14 to March 26), which was 9.41 (95% CI:8.24-10.91). Conclusion The shorter the doubling time, the faster the speed of influenza transmission, and it is necessary to strengthen the prevention and control of influenza in winter and spring.

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

Knee osteoarthritis (KOA) is a common chronic degenerative disease that not only causes pain and reduces the quality of life for patients but also imposes a significant societal burden. Clinical pathways can be developed by referencing recommendations from clinical practice guidelines to localize guidelines within the context of integrated traditional Chinese and western medical systems. However, existing clinical pathways suffer from shortcomings such as deficiencies in integrated traditional Chinese and western medical diagnosis and treatment, inadequate shared decision-making between healthcare providers and patients, and suboptimal visualization of clinical pathways. This study aimed to address and optimize the clinical pathway of KOA by comprehensively organizing and localizing the recommended guidelines. The concept of integrated traditional Chinese and western medicine was reflected through the construction of a path of joint decision-making between doctors and patients, emphasizing the coexistence of diagnosis and screening, the combination of clinical and imaging staging, joint decision-making between doctors and patients, and treatment stages. This pathway emphasizes patient-centered approach, with pain relief and functional rehabilitation running parallel, achieving the implementation of evidence-based concepts in practical medical practice. It provides a concrete basis for joint decision-making between doctors and patients in the integrated treatment of KOA with traditional Chinese and western medicine, which helps to improve diagnosis and treatment efficiency and patient quality of life.

Objective To explore the correlation between cardiac remodeling and the occurrence of contrast-associated acute kidney injury(CA-AKI)assessed by echocardiography.Methods A retrospective analysis was conducted on the clinical data of 100 patients with coronary artery disease(CAD)who underwent coronary angiography(CAG)and percutaneous coronary intervention(PCI)from March 2021 to March 2024.The patients were divided into CA-AKI group and non-CA-AKI group according to whether CA-AKI occurred.Baseline data and echocardiographic parameters,inclu-ding left ventricular end-diastolic internal diameter index(LVIDDI),left ventricular end-systolic in-ternal diameter index(LVIDSI),and left ventricular mass index(LVMI),were collected and com-pared between the two groups.Logistic regression analysis was used to screen for independent influen-cing factors of CA-AKI occurrence.Results The level of N-terminal pro-B-type natriuretic peptide(NT-proBNP)in the CA-AKI group was higher than that in the non-CA-AKI group,and the difference was statistically significant(P＜0.001).Compared with the non-CA-AKI group,the CA-AKI group had higher levels of C-reactive protein and glycosylated hemoglobin(HbA1c),as well as a higher proportion of patients with diabetes and anemia,and the differences were statistically significant(P＜0.05).Echocardiographic data showed that LVMI,LVIDDI,and LVIDSI in the CA-AKI group were all higher than those in the non-CA-AKI group,and the differences were statistically sig-nificant(t=2.057,3.429,2.975;P＜0.05).The left ventricular ejection fraction(LVEF)level in the CA-AKI group was lower than that in the non-CA-AKI group,and the difference was statisti-cally significant(t=3.005,P=0.003).Univariate Logistic regression analysis showed that diabe-tes,anemia,inflammation,NT-proBNP,HbA1c,LVMI,LVIDDI,LVIDSI,LVEF,ventricular hy-pertrophy,and ventricular dilation were significantly associated with the occurrence of CA-AKI(P＜0.05).Multivariate Logistic regression analysis results showed that LVMI(OR=3.81;95％CI,1.04 to 8.50;P=0.045),LVIDDI(OR=4.21;95％CI,2.02 to 6.08;P＜0.001),LVIDSI(OR=1.61;95％CI,1.27 to 2.03;P=0.024),ventricular hypertrophy(OR=3.42;95％CI,1.83 to 4.44;P=0.001),and ventricular dilation(OR=2.93;95％CI,1.43 to 3.74;P=0.033)were independent influencing factors for the occurrence of CA-AKI.Conclusion Cardiac remodeling is significantly correlated with the risk of CA-AKI in CAD patients.Clinicians should take protective measures timely for patients with abnormal cardiac structure to prevent the occurrence of CA-AKI.

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.

Objective To generate minichromosome maintenance protein 2(MCM2)gene knockout cervi-cal cancer HeLa cell lines using inducible CRISPR/Cas9 technology,and to explore the effect of MCM2 on DNA replication and replication stress.Methods The inducible CRISPR/Cas9 system,TLCV2,was used to construct MCM2 knockout HeLa cell lines.And the cell lines were divided into control group(Control),knockout group 1(KO1),and knockout group 2(KO2).Western blot,Edu incorporation experiment,real-time quantitative PCR(qPCR),immunofluorescence and MTT assay were used to analyze the effects of MCM2 knockout on DNA replica-tion and replication stress induced by hydroxyurea.Results The CRISPR/Cas9 system successfully knocked out the MCM2 gene after induction,and MCM2 knockout affected the stability of MCM2-7 complex.Compared with the control cells,MCM2 knockout cells had a dramatic decrease in the capacity of DNA replication,and the mRNA levels of Cyclin A1,Cyclin E1 and CDK4.Under DNA replication stress,MCM2 knockout cells decreased cell viability,DNA damage repair capacity,and increased genomic instability compared with control cells.Conclusion Knockout of MCM2 gene reduces the DNA replication capacity of HeLa cells under normal conditions and cell viability under replication stress.This study successfully generates MCM2 gene inducible knockout HeLa cell lines,laying the foundation for further research on the role and biological function of MCM2 gene in the occurrence and progression of cervical cancer.

Objective To assess the risk factors for systemic inflammatory response syndrome(SIRS)induced by flexible ureteroscopic lithotripsy(FURL)and compare the diagnostic value of bacterial culture for stone,midstream urine culture and pelvic urine culture in predicting postoperative infection.Methods Patients who underwent FURL for upper urinary tract stones from November 2021 to May 2023 were retrospectively enrolled.The patients were divided into non-SIRS and SIRS groups.We collected midstream urine one day before surgery and stone and pelvic urine samples during surgery.Multivariate lo-gistic regression analysis was used to identify the risk factors for SIRS induced by FURL.Results Totally,326 patients,11.66％(38/326)developed SIRS,and 4.29％(14/326)had severe sepsis.The percentages of positive bacterial cultures for mid-stream urine,pelvic urine and stone cultures were 16.87％(55/326),10.43％(34/326)and 15.95％(52/326),respectively.In the multivariate logistic regression analysis,stone size(P=0.010),operation time(P=0.030),and stone culture(P＜0.01)were identified as independent risk factors for SIRS induced by FURL.Positive bacterial culture for stone was an independent risk factor for postoperative severe sepsis(P=0.047).E.coli was the most common pathogen cultured from the three sam-ples.Compared with midstream urine and pelvic urine,a greater proportion of E.coli in stone were resistant to aminoglycoside and β-lactamase antibiotics.Conclusion Positive bacterial culture for stone was associated with an increased incidence of post-operative SIRS.Bacterial culture for stone might have important clinical value in the treatment of postoperative infection in FURL patients.

Objective:To construct a nomogram model for differentiating gastric schwannoma (GS) from gastric stromal tumor (GST) (diameters 2 to 5 cm) based on CT imaging features before surgery.Methods:The clinical and imaging data of 49 patients with GS and 240 patients with GST in the Affiliated Hospital of Jining Medical University from July 2009 to April 2023 and Guangdong Provincial People′s Hospital from June 2017 to September 2022 were analyzed retrospectively. The independent factors for differentiating GS from GST were obtained by multivariate Logistic regression analysis. The nomogram model was constructed by R4.3.1 software. The efficacy of the nomogram model for differentiating GS from GST was evaluated by the receiver operating characteristics (ROC) curve, and calibration curve and decision curve analysis were used to evaluate the predictive efficacy and clinical application value of the nomogram model.Results:There were no statistical differences in the clinical symptom rate, calcification rate, ulcer rate, tumor vessel rate, ratio of long diameter to short diameter and CT value difference during the arterial and nonenhanced phases (CTV A-N) between GS patients and GST patients ( P>0.05). The proportion of female, incidence of lesions located in central or lower part of stomach, extraluminal or mixed growth rate, tumor-associated lymph node rate, strong enhancement rate, CT value difference during the portal and nonenhanced phases (CTV P-N), CT value difference during the delayed and nonenhanced phases (CTV D-N), CT value difference during the portal and arterial phases (CTV P-A) and CT value difference during the delayed and portal phases (CTV D-P) in GS patients were significantly higher than those in GST patients: 75.51% (37/49) vs. 58.33% (140/240), 85.71% (42/49) vs. 54.17% (130/240), 75.51% (37/49) vs. 45.00% (108/240), 44.90% (22/49) vs. 5.42% (13/240), 51.02% (25/49) vs. 27.08% (65/240), 32.0 (26.0, 43.5) HU vs. 29.0 (22.0, 37.7) HU, (44.59 ± 13.46) HU vs. (32.94 ± 12.47) HU, 20.0 (11.5, 25.0) HU vs. 10.0 (5.0, 17.0) HU and 9.0 (6.0, 12.0) HU vs. 4.0 (-2.7, 7.0) HU, the age, irregular shape rate, cystic degeneration rate and heterogeneous enhancement rate were significantly lower than those in GST patients: (58.12 ± 12.59) years old vs. (62.05 ± 11.22) years old, 16.33% (8/49) vs. 38.33% (92/240), 18.37% (9/49) vs. 51.25% (123/240) and 34.69% (17/49) vs. 56.25% (135/240), and there were statistical differences ( P<0.05 or<0.01). Multivariate Logistic regression analysis result showed that location, cystic degeneration, tumor-associated lymph node, CTV P-A and CTV D-P were the independent factors for differentiating GS from GST ( OR= 3.599, 0.201, 19.031, 1.124 and 1.160; 95% CI 1.184 to 10.938, 0.070 to 0.578, 6.159 to 58.809, 1.066 to 1.185 and 1.094 to 1.231; P<0.05 or<0.01). The nomogram model for differentiating GS from GST was constructed based on location, cystic degeneration, tumor-associated lymph node, CTV P-A and CTV D-P. The area under curve of the nomogram model for differentiating GS from GST was 0.924 (95% CI 0.887 to 0.951). The calibration curve analysis result showed that there was a good agreement between the predicted GS curve and the actual GS curve (the mean absolute error was 0.033). The result of the Hosmer-Lemeshow goodness-of-fit test indicated that the calibration of the nomogram model was appropriate ( χ2 = 2.52, P = 0.961). The clinical decision curve analysis result showed that when the threshold for the nomogram model for differentiating the two tumors was>0.03, the nomogram yielded more net benefits than the "all patients treated as GS" or "all patients treated as GST" scenarios. Conclusions:The nomogram model based on CT imaging features can be used to differentiate GS from GST before surgery.