ObjectiveTo investigate the association between the maintenance treatment of modified Yiqi Huoxue Jiedu Formula （益气活血解毒方） or poly ADP ribose polymerase （PARP） inhibitors and the recurrence and metastasis of advanced ovarian cancer. MethodsA case-control study design was employed， dividing patients with advanced ovarian cancer into two groups based on the occurrence of recurrence and metastasis following first-line maintenance treatment. Patients with recurrence and metastasis comprised the case group， while those without recurrence and metastasis served as the control group. The previous first-line maintenance treatment method was set as the exposure factor in the study （with the use of modified Yiqi Huoxue Jiedu Formula defined as exposed and PARP inhibitors defined as unexposed）. Basic information was collected for both groups， including the achievement of satisfactory R0 surgery， age， stage， neoadjuvant chemotherapy， lymph node metastasis， germline BRCA1/2 mutations， homologous recombination deficiency positivity， first-line maintenance treatment method （modified Yiqi Huoxue Jiedu Formula or PARP inhibitors）， and CA125 levels after the last chemotherapy. The baseline data of the two groups were assessed for differences. If there exists difference， a 1∶1 nearest neighbor matching method was used for propensity score matching. Univariate and multivariate logistic regression analyses were employed to evaluate the association between the modified Yiqi Huoxue Jiedu Formula or PARP inhibitors and the recurrence and metastasis of ovarian cancer. ResultsA total of 201 patients with advanced ovarian cancer were included， with 97 in the case group and 104 in the control group. Both groups showed statistically significant differences in R0 surgery， stage， neoadjuvant chemotherapy， and CA125 levels after the last chemotherapy （P＜0.05）， indicating baseline imbalance. After propensity score matching， there were 71 patients in both the case and control groups， achieving baseline balance （P＞0.05）. Univariate logistic regression analysis indicated that the achievement of satisfactory R0 surgery （P = 0.006）， disease stage （P = 0.001）， the use of neoadjuvant chemotherapy （P = 0.024）， treatment modality （P = 0.006）， and CA125 levels after the last chemotherapy （P = 0.013） were associated with the recurrence and metastasis of ovarian cancer. Multivariate logistic regression analysis revealed that disease stage was an independent influencing factor for the recurrence and metastasis of ovarian cancer （P = 0.030）， whereas the P-value for the correlation between first-line maintenance treatment and ovarian cancer was 0.188. ConclusionFirst-line maintenance treatment of ovarian cancer patients with the use of modified Yiqi Huoxue Jiedu Formula or PARP inhibitors does not correlate with the recurrence and metastasis of ovarian cancer.

ObjectiveTo analyze the distribution of traditional Chinese medicine （TCM） syndrome elements in patients with immune-related adverse events （irAEs） associated with malignant tumor immunotherapy and to explore the influencing factors for the occurrence of irAEs. MethodsClinical data were retrospectively collected from malignant tumor patients treated with programmed death-1 （PD-1） inhibitors， including demographic information， tumor history， duration of immunotherapy， occurrence of irAEs， types and grades of irAEs （G1-G5）， and TCM four-diagnostic information. Patients were divided into irAEs group and the non-irAEs group based on the occurrence of irAEs. Propensity score matching （PSM） at a 1∶2 ratio was performed to balance baseline characteristics between groups. Syndrome elements before treatment and cumulative contributions of syndrome elements before and after irAEs onset were evaluated using the "Syndrome Elements Differentiation Scale". Logistic regression analysis was conducted to identify factors associated with the occurrence of irAEs. The use of glucocorticoids in the irAEs group was also analyzed. ResultsAfter 1∶2 matching， 59 patients were included in the irAEs group and 118 were in the non-irAEs group. No statistically significant differences were found between groups in terms of age， gender， primary tumor site， pathological type， or tumor stage （P＞0.05）. Patients in the non-irAEs group were more likely to have received targeted therapy， while the irAEs group had a longer duration of immunotherapy and a higher rate of positive programmed death-ligand 1 （PD-L1） expression （P＜0.05）. In total， 72 irAEs events occurred among 59 patients， with an overall incidence rate of 19.4% （59/304） and a grade 3~5 incidence rate of 6.8% （4/59）， mainly presenting as cardiotoxicity， nephrotoxicity， and pneumotoxicity.Before immunotherapy， the top three syndrome elements in the irAEs group were spleen （71.2%， 42/59）， kidney （42.4%， 25/59）， and lung （39.0%， 23/59）. For the pathogenic nature elements， yin deficiency （52.5%， 31/59）， phlegm （40.7%， 24/59）， and dampness （35.6%， 21/59） ranked highest. Compared to the non-irAEs group， the distribution of spleen， kidney， liver， yin deficiency， and qi deficiency elements showed significant differences in the irAEs group （P＜0.05）. After the occurrence of irAEs， the cumulative contributions of spleen， lung， stomach， heart， yin deficiency， qi deficiency， and yang hyperactivity elements increased significantly （P＜0.05）. Multivariate Logistic regression analysis indicated that duration of immunotherapy， spleen syndrome element， kidney syndrome element， liver syndrome element， yin deficiency element， and qi deficiency element were independent risk factors for irAEs （P＜0.05 or P＜0.01）. Among the irAEs patients， 15 received glucocorticoid combined with TCM treatment， while 6 received glucocorticoid therapy alone. Patients receiving combined treatment required lower doses and shorter courses of glucocorticoids compared to those treated with glucocorticoids alone （P＜0.05）. ConclusionIn malignant tumor patients， spleen， kidney， lung， yin deficiency， phlegm， dampness， and qi deficiency are the predominant syndrome elements before and after the occurrence of irAEs. However， elements such as heat and qi stagnation significantly increase after irAEs onset. Duration of immunotherapy， spleen， kidney， liver syndrome elements， yin deficiency， and qi deficiency are independent risk factors for the development of irAEs.

There are limited reports available regarding the treatment of amputated noses. This article presented a case of an incompletely amputated nose in a 47-year-old male who was admitted to Dalian University Affiliated Xinhua Hospital in July 2023. He was characterized by an amputated right nasal tip and alar region, with an avulsion area of approximately 4 cm×4 cm. The broad pedicle was connected to the nasal base, approximately 5 mm below the remaining nasal column, and only the nasal column retained a satisfactory arterial blood supply. During the operation, the amputated tissue was implanted in situ, and clindamycin was employed to prevent infection after the operation by intravenous infusion. Bloodletting with flaps, wet application of heparin saline, and massage were employed and all the amputated tissue survived. The appearance of the nose was deemed acceptable. By reviewing relevant literature, the author discussed and summarized the methods of nasal blood supply and treatment for nasal amputated injuries, thereby providing a reference for the management of similar cases.

There are limited reports available regarding the treatment of amputated noses. This article presented a case of an incompletely amputated nose in a 47-year-old male who was admitted to Dalian University Affiliated Xinhua Hospital in July 2023. He was characterized by an amputated right nasal tip and alar region, with an avulsion area of approximately 4 cm×4 cm. The broad pedicle was connected to the nasal base, approximately 5 mm below the remaining nasal column, and only the nasal column retained a satisfactory arterial blood supply. During the operation, the amputated tissue was implanted in situ, and clindamycin was employed to prevent infection after the operation by intravenous infusion. Bloodletting with flaps, wet application of heparin saline, and massage were employed and all the amputated tissue survived. The appearance of the nose was deemed acceptable. By reviewing relevant literature, the author discussed and summarized the methods of nasal blood supply and treatment for nasal amputated injuries, thereby providing a reference for the management of similar cases.

Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

Objective To explore the current situation and influencing factors that affect stroke specialist nurses in Henan Province and provide a reference for targeted interventions.Methods A total of 140 stroke specialist nurses from over 103 general hospitals in Henan Province were selected to participate the study with the convenience sampling method,between March and November 2022.General data questionnaire and the core competence evaluation questionnaire of stroke specialist nurses in Henan Province were employed for the investigation.Influencing factors were analysed by binary Logistic regression.Results A total of 134 specialist nurses responded to the survey.The findings revealed that the total score of core competence in the stroke specialist nurses was 279.5(257.0,306.0).Among the dimensions of core competence,the clinical thinking ability scored the highest at 4.4(4.0,4.9),while professional development ability scored the lowest at 3.7(3.4,4.0).Cluster analysis categorised that the scores＜250 were of a low score group(n=26)and those≥250 were of a high score group(n=108).Binary Logistic regression analysis indicated that education level,years working as a stroke specialist nurse,and the working experience in the stoke fast track team of A&E were the factors that influenced the core competence of the stroke specialist nurses in Henan Province(all P＜0.05).Conclusions This study has found that the core competence of stroke specialist nurses in Henan Province is at an acceptable level.Education,years working as a stroke specialist nurse and the working experience in the fast track team of A&E are the primary factors which influence core competence.Nursing managers should devise supportive programs to target the influencing factors and to improve the core competence of the stroke specialist nurses.

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activ-ity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

OBJECTIVE To study the absorption characteristics of phenylpropanoids of Mongolian medicine Tabson-2 decoction(TBD) in Caco-2 cells and to preliminarily clarify the oral absorption mechanism of TBD. METHODS Caco-2 cell monolayer model was used to analyze the uptake components of TBD in Caco-2 cells by UPLC-MS/MS, and UPLC-MS/MS analysis method was established to determine the nine best absorbed components of TBD, protocatechuic acid, neochlorogenic acid, chlorogenic acid, cryptogenic acid, 1,5-dicaffeinate quinic acid, isochlorogenic acid C, caffeic acid, dihydrocaffeic acid, chlorogenic acid. The effects of time, concentration and P-glycoprotein inhibitor on the absorption of each component were investigated. RESULTS The overall intake of caffeic acid and dihydrocaffeic acid showed an upward trend in 0-180 min, and did not show saturation. The absorption of 3-hydroxycinnamic acid was constant at about 90 min and tended to saturation. The intakes of cryptochlorogenic acid, 1,5-dicaffeinate, quinic acid, isochlorogenic acid C, neochlorogenic acid, chlorogenic acid and protocatechuic acid first decreased and then increased with time from about 90 min. The addition of P-glycoprotein inhibitor verapamil and cyclosporin A had an effect on the absorption of dihydrocaffeic acid compared with the phenylpropanoid components, indicated that dihydrocaffeic acid was the substrate of P-glycoprotein. CONCLUSION The main phenylpropanoids of TBD enter Caco-2 mainly by passive diffusion, supplemented by active transport, and the absorption process of the other eight components is not affected by the efflux of P-glycoprotein except dihydrocaffeic acid.

Objective:To compare the differences of brain activation in patients with neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) under contact heat stimulation (CHS), and to explore the characteristics of pain-related brain networks in NMOSD and MS patients.Methods:Fourteen NMOSD patients (NMOSD group) and 12 MS patients (MS group) admitted to Affiliated Hospital of North Sichuan Medical College from September 2022 to December 2022 who met the diagnostic criteria were collected. Twelve healthy individuals (HC group) matched with gender and age were recruited during the same period. Visual Analogue Scale (VAS) score was used to evaluate the pain of the subjects, CHS painful stimuli were given, and task-state functional magnetic resonance imaging (fMRI) scans were performed at the same time, and the differences in brain activation among the 3 groups were analyzed and compared.Results:(1) Compared with the HC group, the NMOSD group had a stronger activation degree than the HC group in the brain regions including the cortex around the left distance fissure, bilateral medial superior frontal gyrus; the activation degree of the NMOSD group was weaker than that of the HC group in the brain areas including the left medial and paracingulate gyrus, right superior parietal gyrus, left postcentral gyrus, and right supplementary motor area (all P<0.05). (2) Compared with the HC group, the brain regions whose activation degree was weaker in the MS group included the left caudate nucleus, left medial and paracingulate gyrus, left paracentral lobule, right superior parietal gyrus, left postcentral gyrus, left precuneus, right supplementary motor area, right superior temporal gyrus and right thalamus, and there was no brain area in the MS group whose activation degree was stronger than that of the HC group (all P<0.05). (3) Compared with the MS group, the brain regions with stronger activation degree in the NMOSD group included the left perifissure cortex and right thalamus, but no brain regions with weaker activation degree were found in the NMOSD group (all P<0.05). (4) There was a correlation between somatic pain VAS scores and activation of the medial superior frontal gyrus in the NMOSD group ( r=0.66, P<0.05). Conclusions:The results of CHS-fMRI in the NMOSD group, MS group and HC group showed that multiple brain regions were activated, indicating that multiple brain regions were involved in the generation and processing of pain, and there was a pain-related brain network. Pain-related brain networks were altered in NMOSD patients and MS patients, and there were differences in pain-related brain networks between the two diseases.

Objective:To observe the changes in brain functional magnetic resonance imaging (fMRI) in migraine patients under olfactory stimuli and analyze the characteristics of olfactory-related brain networks.Methods:Twenty-seven migraine patients (migraine group) enrolled in the Department of Neurology, Affiliated Hospital of North Sichuan Medical College from January 2021 to January 2022 were included, and 20 healthy adults were recruited as control group during the same period. All subjects underwent synchronous fMRI scanning under olfactory task stimulation, and magnetic resonance imaging data processing was performed using SPM12 and Matlab2019b softwares, and statistical analysis was performed with SPSS 23.0 software.Results:The activated brain regions in the control group included the left cerebellum, left inferior temporal gyrus, left fusiform gyrus, right middle frontal gyrus, right anterior central gyrus, insula, right central sulcus, superior marginal gyrus, right lenticular putamen, middle cingulate gyrus, paracentral lobule, and superior parietal gyrus ( P<0.05). The activated brain regions in the migraine group included the left cerebellum, right fusiform gyrus, right inferior temporal gyrus, right anterior central gyrus, and right posterior central gyrus ( P<0.05). Compared with the control group, the activation intensity of the migraine group was weaker in the right insula, right middle frontal gyrus orbit, left inferior frontal gyrus orbit, right dorsolateral superior frontal gyrus, right superior temporal gyrus, right superior occipital gyrus, medial and paracingulate gyrus, and right superior parietal gyrus ( P<0.05). Conclusion:Migraine patients have multiple brain regions involved in olfactory processing and have specific olfactory-related brain networks.