OBJECTIVES: To investigate the therapeutic mechanism of Huoxue Shufeng Granules (HXSFG) for alleviating central sensitization in a mouse model of chronic migraine (CM). METHODS: We analyzed the main chemical components of HXSFG through literature review and explored their pharmacological mechanisms by bioinformatics analyses. In a male C57BL/6J mouse model of CM established by intraperitoneal injections of nitroglycerin (10 mg/kg) every other day (5 injections), the effects of gavage with low, and high doses of HXSFG or intraperitoneal injections of topiramate for ameliorating central sensitization were evaluated using Von Frey test and a hot plate apparatus; the changes in expressions of inflammatory factors, the proteins in the TLR4/NF‑κB signaling pathway, and activation of c-Fos and CGRP were detected using RT-qPCR, Western blotting and immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that the main active components in HXSFG for alleviating CM included formononetin, paeoniflorin, quercetin, and tanshinone. Gene Ontology (GO) enrichment analysis identified 492 GO entries, comprising 366 biological processes, 46 cellular components, and 80 molecular functions. KEGG pathway enrichment analysis indicated that the Toll-like receptor and NF‑κB signaling pathways were crucial in mediating the therapeutic effects of HXSFG on CM. In the mouse models of CM, both topiramate and HXSFG treatments alleviated the symptoms of central sensitization, evidenced by improved mechanical and thermal pain thresholds in the mice. HXSFG significantly reduced the expression of c-Fos and CGRP, improved inflammatory markers, and downregulated the expressions of TLR4, p-NF‑κB, IL-1β, and TNF‑α proteins in the mouse models. CONCLUSIONS HXSFG effectively alleviates central sensitization in CM mice by modulating the inflammatory pathways and inhibiting the TLR4/ NF-κB signaling pathway, suggesting its potential as a therapeutic option for CM.
Animals ; Toll-Like Receptor 4/metabolism* ; NF-kappa B/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Male ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Migraine Disorders/metabolism* ; Disease Models, Animal ; Inflammation

Objective:To explore the value of ultrasound imaging characteristics combined with clinical indicators in assessing the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:A retrospective analysis was conducted for patients who underwent pancreatic contrast-enhanced ultrasound (CEUS) from September 2017 to October 2023 at Peking Union Medical College Hospital and were diagnosed with PDAC based on pathological findings. Various parameters were recorded, including CA19-9 levels, tumor size, location, morphologic features, echogenicity, presence of internal cystic components, dilatation of the main pancreatic duct, peripheral vascular invasion, CEUS characteristics, presence or absence of liver metastasis, and treatment methods. In April 2024, patient survival information was obtained through telephone follow-up or review of medical records. Based on the results of the cox regression model analysis, a nomogram model of the risk of death was developed. The receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of the model. The calibration curves were plotted to evaluate the accuracy of the model, and clinical decision curves were used to evaluate the clinical benefit of the model.Results:This study included a total of 207 patients with PDAC. As of April 2024, 71 patients were alive and 136 died, with a median survival time of 14 months (95% CI: 12 -17). Multivariate analysis confirmed that the elevated CA19-9 ( HR=1.689, 95% CI: 1.102-2.588), tumor size >4 cm ( HR=1.641, 95% CI: 1.159-2.322), taller-than-wide shapes ( HR=1.450, 95% CI: 1.019-2.065), incomplete hypo-enhancement ( HR=1.618, 95% CI: 1.100-2.380), and liver metastasis ( HR=1.687, 95% CI: 1.175-2.423) were independent risk factors for survival in patients with PDAC. A nomogram model was further constructed for 6-month, 12-month and 3-year survival of patients with PDAC. The areas under the ROC curve were 0.679, 0.705 and 0.815, respectively. The calibration curves suggested that the model was more accurate, and the clinical decision curves showed that the model had a better clinical benefit. Conclusion:The combined use of ultrasound imaging characteristics and clinical indicators could effectively predict the prognosis of PDAC patients. Specifically, tumor size >4 cm, taller-than-wide shapes, incomplete hypo-enhancement, elevated CA19-9, and the presence of liver metastasis are correlated with poorer survival outcomes. The nomogram model constructed on the basis of these factors can be used to assess the survival of patients with PDAC.

Objective:To explore the value of ultrasound imaging characteristics combined with clinical indicators in assessing the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:A retrospective analysis was conducted for patients who underwent pancreatic contrast-enhanced ultrasound (CEUS) from September 2017 to October 2023 at Peking Union Medical College Hospital and were diagnosed with PDAC based on pathological findings. Various parameters were recorded, including CA19-9 levels, tumor size, location, morphologic features, echogenicity, presence of internal cystic components, dilatation of the main pancreatic duct, peripheral vascular invasion, CEUS characteristics, presence or absence of liver metastasis, and treatment methods. In April 2024, patient survival information was obtained through telephone follow-up or review of medical records. Based on the results of the cox regression model analysis, a nomogram model of the risk of death was developed. The receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of the model. The calibration curves were plotted to evaluate the accuracy of the model, and clinical decision curves were used to evaluate the clinical benefit of the model.Results:This study included a total of 207 patients with PDAC. As of April 2024, 71 patients were alive and 136 died, with a median survival time of 14 months (95% CI: 12 -17). Multivariate analysis confirmed that the elevated CA19-9 ( HR=1.689, 95% CI: 1.102-2.588), tumor size >4 cm ( HR=1.641, 95% CI: 1.159-2.322), taller-than-wide shapes ( HR=1.450, 95% CI: 1.019-2.065), incomplete hypo-enhancement ( HR=1.618, 95% CI: 1.100-2.380), and liver metastasis ( HR=1.687, 95% CI: 1.175-2.423) were independent risk factors for survival in patients with PDAC. A nomogram model was further constructed for 6-month, 12-month and 3-year survival of patients with PDAC. The areas under the ROC curve were 0.679, 0.705 and 0.815, respectively. The calibration curves suggested that the model was more accurate, and the clinical decision curves showed that the model had a better clinical benefit. Conclusion:The combined use of ultrasound imaging characteristics and clinical indicators could effectively predict the prognosis of PDAC patients. Specifically, tumor size >4 cm, taller-than-wide shapes, incomplete hypo-enhancement, elevated CA19-9, and the presence of liver metastasis are correlated with poorer survival outcomes. The nomogram model constructed on the basis of these factors can be used to assess the survival of patients with PDAC.

Objective To observe the value of contrast-enhanced ultrasound(CEUS)for evaluating blood supply pattern of pancreatic ductal adenocarcinoma(PDAC).Methods A total of 210 single PDAC patients proved by pathology who underwent CEUS and contrast enhanced CT(CECT)examination were retrospectively enrolled.Blood supply patterns of PDAC,i.e.deficient or rich blood supply were evaluated based on findings of CEUS 25 s(CEUS-25 s)and 35 s(CEUS-35 s)after contrast agents injection and CECT,respectively.The evaluation results were compared among different methods.Disease free survival(DFS)and overall survival(OS)of patients with deficient and rich blood supply PDAC shown on CEUS-25 s were followed up and compared.Results CEUS-25 s found 60.00％(126/210)PDAC with deficient blood supply(poor blood supply group),while 40.00％(84/210)with rich blood supply(rich blood supply group).CEUS-35 s showed that the proportion deficient blood supply PDAC increased to 70.48％(148/210,P＜0.05),22 lesions changed from rich blood supply pattern on CEUS-25 s to deficient blood supply pattern.CECT displayed deficient blood supply in 91.90％(193/210)PDAC but rich blood supply in 8.10％(17/210)PDAC,both being significant different compared with results of CEUS-25 s and CEUS-35 s(both P＜0.05).Fifteen-five cases in deficient blood supply group and 39 in rich blood supply group completed 12(8,25)months'follow-up,and the median DFS of patients in deficient blood supply group and rich blood supply group was 8(6,10)and 12(7,17)months,respectively,with the median OS of 14(9,17)and 19(16,24)months,respectively.The median DFS and OS in poor blood supply group were both shorter than those in rich blood supply group(x2=17.227,27.166,both P＜0.001).Conclusion CEUS had important clinical value for evaluating blood supply pattern of PDAC.

Objective To explore the preventive and therapeutic effects of Caryopteris incana decoction in a rat model of primary dysmenorrhea with cold coagulation and blood stasis syndrome.Methods Sixty healthy specific pathogen-free SD female rats were randomly divided into six groups of ten rats each:normal group,model group,ibuprofen group,C.incana high-dose group,C.incana medium-dose group,and C.incana low-dose group.All groups except the normal group were treated with cold stimulation combined with estradiol benzoate and oxytocin to establish a rat model of primary dysmenorrhea with cold coagulation and blood stasis syndrome.On the fifth day of modeling,the rats were intragastrically administered the study drugs for 10 days.Their symptoms were observed and recorded.The writhing response and hemorheological indices were measured.The serum levels of TXB2,6-keto-prostaglandin F1α(6-Keto-PGF1α),estradiol(E2),and progesterone(PROG)were measured.Additionally,the levels of prostaglandin F2α(PGF2α),prostaglandin E2(PGE2),nitric oxide(NO),and calcium(Ca2+)in the uterine tissues were measured.The organ indices of the uterus and ovary were calculated,and histopathological changes were observed.Results Compared with the normal group,the rats in the model group showed obvious symptoms of cold coagulation and blood stasis syndrome and writhing reaction.The morphology of uterus and ovary showed obvious hyperplasia,inflammation,edema and other lesions.The plasma viscosity,packed cell volume and whole blood viscosity were significantly increased(P＜0.01).The serum levels of thromboxane B2 and E2 and the E2/PROG ratio were significantly increased(P＜0.01),the levels of 6-Keto-PGF1α and PROG were significantly decreased(P＜0.01).The uterine index and ovarian index were significantly increased(P＜0.01).The levels of PGF2α and Ca2+and the PGF2α/PGE2 ratio in uterine tissue were significantly increased(P＜0.01),while the levels of PGE2 and NO were significantly decreased(P＜0.01).Compared with the model group,Caryopteris incana significantly improved the symptoms of model rats,improved the morphological lesions of the uterus and ovary,prolonged the latency time of the writhing reaction,and reduced the number of writhing episodes(P＜0.01);significantly reduced the plasma viscosity,packed cell volume,and whole blood viscosity(P＜0.01);significantly reduced the serum levels of TXB2 and E2 and the E2/PROG ratio,increased the serum levels of 6-Keto-PGF1αand PROG,and reduced the uterine and ovarian indices(P＜0.01,P＜0.05);significantly reduced the levels of PGF2αand Ca2+and the PGF2α/PGE2 ratio in uterine tissue(P＜0.01,P＜0.05);and significantly increased the levels of PGE2 and NO in the uterine tissue(P＜0.01).Conclusions Caryopteris incana decoction can effectively improve the clinical symptoms of primary dysmenorrhea in rats with cold coagulation and blood stasis syndrome,and it has a good control effect.Its mechanism may be correlated with the levels of TXB2,6-Keto-PGF1α,E2,and PROG in serum and PGF2α,PGE2,NO,and Ca2+in uterine tissue.

To evaluate the accuracy of contrast-enhanced ultrasound diagnostic reports for pancreatic lesions.

Objective To observe the value of contrast-enhanced ultrasound(CEUS)for evaluating blood supply pattern of pancreatic ductal adenocarcinoma(PDAC).Methods A total of 210 single PDAC patients proved by pathology who underwent CEUS and contrast enhanced CT(CECT)examination were retrospectively enrolled.Blood supply patterns of PDAC,i.e.deficient or rich blood supply were evaluated based on findings of CEUS 25 s(CEUS-25 s)and 35 s(CEUS-35 s)after contrast agents injection and CECT,respectively.The evaluation results were compared among different methods.Disease free survival(DFS)and overall survival(OS)of patients with deficient and rich blood supply PDAC shown on CEUS-25 s were followed up and compared.Results CEUS-25 s found 60.00％(126/210)PDAC with deficient blood supply(poor blood supply group),while 40.00％(84/210)with rich blood supply(rich blood supply group).CEUS-35 s showed that the proportion deficient blood supply PDAC increased to 70.48％(148/210,P＜0.05),22 lesions changed from rich blood supply pattern on CEUS-25 s to deficient blood supply pattern.CECT displayed deficient blood supply in 91.90％(193/210)PDAC but rich blood supply in 8.10％(17/210)PDAC,both being significant different compared with results of CEUS-25 s and CEUS-35 s(both P＜0.05).Fifteen-five cases in deficient blood supply group and 39 in rich blood supply group completed 12(8,25)months'follow-up,and the median DFS of patients in deficient blood supply group and rich blood supply group was 8(6,10)and 12(7,17)months,respectively,with the median OS of 14(9,17)and 19(16,24)months,respectively.The median DFS and OS in poor blood supply group were both shorter than those in rich blood supply group(x2=17.227,27.166,both P＜0.001).Conclusion CEUS had important clinical value for evaluating blood supply pattern of PDAC.

Objective:To analyze the predictive value of serological measures within 24 hours of admission in acute pancreatitis patients against patients with severe acute pancreatitis(SAP), because the severity of acute pancreatitis was characterized by a timely assessment and prediction by emergency department physicians upon visit.Methods:A total of 119 acute pancreatitis patients admitted in Emergency Department in Beijing Jishuitan Hospital, Capital Medical University from January 2022 to December 2022 were retrospectively collected. According to the revised Atlanta classification, patients were characterized by mild acute pancreatitis group (77 cases), moderately severe acute pancreatitis group (27 cases), and SAP group (15 cases). Basic characteristics, early disease severity scores and early serological indexes of the three groups were compared, independent risk factors of serological indexes affecting the occurrence of SAP were analyzed, and receiver operator characteristic curve was drawn, evaluate the predictive value of related serological indexes for SAP.Results:There were no significant differences in the basic characteristics of the three groups including of gender, age, BMI, type of pancreatitis and complications ( P>0.05), but there were significant differences in early BISPA, Ranson, APACHEⅡ and Panc3 scores among the three groups ( P<0.05).Albumin-bilirubin score ( OR=3.653, 95% CI 1.665-8.012, P=0.001), blood urea nitrogen ( OR=1.117, 95% CI 1.039-1.202, P=0.003) were independent risk factors for SAP. The areas under ROC curve predicted by albumin-bilirubin score, blood urea nitrogen and albumin-bilirubin score combined with blood urea nitrogen were 0.762, 0.776 and 0.857, respectively, which showed no statistical difference compared with earlier Ranson, BISAP and APACHE Ⅱ scoring systems, respectively ( P>0.05). Conclusions:Early albumin-bilirubin score and blood urea nitrogen indexes of acute pancreatitis patients have good predictive value for SAP. Albumin-bilirubin score combined with blood urea nitrogen can improve the predictive value of SAP, and the predictive effect is as good as early Ranson, BISAP and APACHEⅡ scoring systems.

Objective:To explore the clinical value of preconception expanded carrier screening (PECS) in Chinese Han population of childbearing age.Methods:The gene detection results of infertile couples with PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University from September 2019 to May 2022 were analyzed retrospectively. The carrier rate of pathogenic gene, the detection rate of high-risk couples and the clinical outcome of high-risk couples were counted and analyzed.Results:A total of 1 565 patients received PECS and they were all Chinese Han. A total of 504 patients received the 108 extended monogenic diseases testing, including 420 females and 84 males, the overall carrier rate of the target genes was 30.75% (129/420), and the detection rate of high-risk couples was 1.19% (1/84), the higher carrier rates of the tested genes were MMACHC [2.58% (13/504)], ATP7B [2.38% (12/504)], SLC22A5 [2.18% (11/504)], GALC [1.79% (9/504)], PAH [1.79% (9/504)] and MLC1 [1.19% (6/504)], the rest are less than 1%. There were 555 patients accepted FMR1 gene detection, and 5 patients with FMR1 gene mutation, accounting for 0.90%. Testing for direct relatives of patients with complete mutations, her mother is a pre mutation carrier with a CGG repeat count of 105. A total of 502 patients accepted SMN1 gene testing. Totally 14 femals and 2 males were found to be SMN1 gene carriers in this study, with a carrier rate of 3.19%. Conclusion:The carryier rate of single gene recessive disorder is high in the population. Screening before pregnancy can provide birth health guidance for patients, help them to choose preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis, to avoid the birth of silk children.

Objective:To explore the clinical value of preconception expanded carrier screening (PECS) in Chinese Han population of childbearing age.Methods:The gene detection results of infertile couples with PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University from September 2019 to May 2022 were analyzed retrospectively. The carrier rate of pathogenic gene, the detection rate of high-risk couples and the clinical outcome of high-risk couples were counted and analyzed.Results:A total of 1 565 patients received PECS and they were all Chinese Han. A total of 504 patients received the 108 extended monogenic diseases testing, including 420 females and 84 males, the overall carrier rate of the target genes was 30.75% (129/420), and the detection rate of high-risk couples was 1.19% (1/84), the higher carrier rates of the tested genes were MMACHC [2.58% (13/504)], ATP7B [2.38% (12/504)], SLC22A5 [2.18% (11/504)], GALC [1.79% (9/504)], PAH [1.79% (9/504)] and MLC1 [1.19% (6/504)], the rest are less than 1%. There were 555 patients accepted FMR1 gene detection, and 5 patients with FMR1 gene mutation, accounting for 0.90%. Testing for direct relatives of patients with complete mutations, her mother is a pre mutation carrier with a CGG repeat count of 105. A total of 502 patients accepted SMN1 gene testing. Totally 14 femals and 2 males were found to be SMN1 gene carriers in this study, with a carrier rate of 3.19%. Conclusion:The carryier rate of single gene recessive disorder is high in the population. Screening before pregnancy can provide birth health guidance for patients, help them to choose preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis, to avoid the birth of silk children.