Objective To identify symptom clusters in breast cancer patients undergoing chemotherapy and investigate the bridge symptoms that connect the symptom clusters,therefore to provide a guidance for precise intervention in the symptoms.Methods From October 2022 to October 2023,convenience sampling method was employed to selelct 340 breast cancer patients,who underwent postoperative chemotherapy,for investigation in the related symptom clusters and quality of life by using Anderson symptom assessment scale and breast cancer quality of life scale.Cluster analysis was performed to extract the symptom clusters by R software and the impacts of each symptom cluster on quality of life were analysed by stratified regression.A contemporaneous symptom network was constructed to identify the bridge symptoms.Results All 327 patients had completed the study.Three distinct symptom clusters were extracted:-gastrointestinal,psychological and neurological symptom clusters.The gastrointestinal cluster alone accounted for 10.2%of the variation in quality of life.Network analysis highlighted that distress(rbe=3.927,rbs=3.927,rbc=0.436),fatigue(rbe=3.907,rbs=3.907,rbc=0.434)and lack of appetite(rbe=3.842,rbs=3.842,rbc=0.427)were the bridging symptoms which had high expected influence coefficient,strength and closeness centrality index.Conclusion The gastrointestinal symptom cluster makes notably impact on the quality of life in breast cancer patients undergoing chemotherapy.Fatigue,lack of appetite and distress are the bridge symptoms in symptom management strategies in potentially improving the efficiency of intervention and reducing the costs to patient.

Objective To examine the protective effect and mechanism of formononetin on rat cardiomyocyte injury induced by hy-poxia/reoxygenation.Methods The H9C2 rat cardiomyocytes were randomly divided into the control group,hypoxia/reoxygenation group,and formononetin group.Cells in the control group were cultured in conventional incubators,and cells in the hypoxia/reoxygenation group were cultured in hypoxia incubators and conventional incubators alternately.Cells in the formononetin group were treated with 35μmol/L formononetin after incubation in the hypoxia/reoxygenation.Cell activity was tested by a cell activity detection kit.The content of oxidative stress and inflammatory response indicators were examined by related test kits.The flow cytometry and polynucleotide chain break detection technology were used to detect apoptosis levels.Western blot was used to detect the levels of apoptosis-related proteins.Results Compared with the control group,cells in the hypoxia/reoxygenation group showed decreased cell activity and increased oxida-tive stress,inflammatory damage,and apoptosis(P＜0.05).Compared with the hypoxia/reoxygenation group,cells of the formononetin group showed increased cell activity and decreased oxidative stress,inflammatory damage,and apoptosis(P＜0.05).Conclusion For-mononetin may protect against hypoxia/reoxygenation injury by reducing the apoptosis of H9C2 rat cardiomyocytes.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective To understand cognition level and treatment intention of patients with endometriosis(EMs);To evaluate the effects of TCM chronic disease management on EMs patients.Methods The disease cognition level and treatment intention of 1 895 EMs patients from October 2020 to December 2021 in 19 provinces,autonomous regions and municipalities were analyzed through cross-sectional investigation.The cognitive effect of chronic disease management of TCM on 801 patients with EMs from 6 Grade A hospitals in Beijing was evaluated by self-control study.Results The cognition level of EMs patients for the disease was improved with the increase of educational background.Patients generally believed that EMs was a chronic disease,requiring regular review and long-term management.The proportion of patients with high school education or below,junior college education,bachelor degree or above who knew the possibility of malignant changes in EMs was less,only 32.3%,41.6%and 47.7%,respectively.The awareness rate of patients with high school education or below for recurrence after EMs conservative surgery was 46.9%,lower than that of those with junior college education(66.8%)and bachelor degree or above(72.7%).Among the patients with dietary contraindications,the proportion of patients with high school education or below,junior college education,bachelor degree or above who knew the contraindication of the forest frog oil was less,only 20.7%,30.3%and 32.9%,respectively.In the aspect of life adjustment,the awareness of patients was generally high.EMs patients mainly recognized the disease through face-to-face communication with gynecologists.Only 34.4%of patients with high school education or below learned about EMs through WeChat public accounts,APPs and other new media,which was lower than those with junior college education(48.6%)and bachelor degree or above(55.4%).EMs patients generally tend to be treated in comprehensive hospitals,with high acceptance of TCM treatment,mainly TCM decoction,and low acceptance of TCM appropriate technology.After 1 year of TCM chronic disease management,the disease awareness of EMs patients was significantly improved compared with before management,with statistical significance(P<0.05).Conclusion EMs patients with different educational backgrounds have different cognition of the disease,and each has different emphasis.Education and popularization should be carried out according to their knowledge blind spots.Chronic disease management of TCM can improve the disease cognition level of EMs patients.

Objective To explore the effect of Huoxue Xiaoyi Formula on ovarian function and pregnancy outcome in endometriosis rats. Methods One hundred female SD rats were fed adaptively for 7 days. According to body weight, 98 rats with a normal estrous cycle were randomly divided into the blank group (n=14), the sham operation group (n=14), the donor group (n=12), and the receptor group (n=58). A rat model of endometriosis was established using allogeneic endometrial transplantation. After the model was successfully established, according to the body weight, 56 rats in the receptor group were randomly divided into the model group, and the Huoxue Xiaoyi Formula low-, medium-, and high-dose groups, with 14 rats in each group. The Huoxue Xiaoyi Formula low-, medium-, and high-dose groups were given 5.86, 11.72, and 23.44 g/kg of Huoxue Xiaoyi Formula, and the blank group, the sham operation group, and the model group were given distilled water by gavage for 15 consecutive days. According to body weight, six rats were randomly selected to take abdominal aortic blood for determination of serum anti-Mullerian hormone (AMH) content by enzyme-linked immunosorbent assay. According to body weight, six rats were randomly selected in the remaining rats to undergo high-frequency small animal ultrasound examination to measure ovarian volume and ovarian artery blood supply (resistance index and pulsatility index), and follicle count were measured. The female mice were fed with male mice at a ratio of 2:1 to observe the pregnancy rate, live fetus number, still fetus number, and absorbed fetus number. The weights of uterus and fetus were measured, while the placental weight, fetal weight, body length, and tail length were measured for live fetus. Bone and visceral malformations were also detected for live fetus. Results There were no significant differences in serum AMH and ovarian volume among the groups. Compared with the model group, the numbers of follicles in the blank group, the sham operation group, and the Huoxue Xiaoyi Formula low-, medium-, and high-dose groups were increased; compared with the Huoxue Xiaoyi Formula low-dose group, the numbers of follicles in the blank group and the Huoxue Xiaoyi Formula medium-dose group were increased (P<0.05). Compared with the model group, the resistance index and pulsatility index of ovarian artery blood flow in the blank group, the sham operation group, and the Huoxue Xiaoyi Formula low-, medium-, and high-dose groups were decreased(P<0.05). There was no significant difference in pregnancy rate among the groups. Compared with the model group and the Huoxue Xiaoyi Formula low-dose group, the live fetus number and the weight of uterus and fetus in the blank group, the sham operation group, and the Huoxue Xiaoyi Formula medium- and high-dose groups were increased (P<0.05). There were no significant differences in the still fetus number, absorbed fetus number, placental weight, fetal weight, body length and tail length among the groups. No visceral or skeletal malformations were found in the live fetal rats among the groups.Conclusion In endometriosis model rats, the ovarian artery blood flow perfusion is insufficient, and the follicle count is reduced, affecting ovary function, thereby reducing the live fetus number. After applying the Huoxue Xiaoyi Formula, it can improve ovarian blood supply, increase the follicle count, and increase the live fetus number. The effect of increasing the live fetus number with the medium- and high-doses of Huoxue Xiaoyi Formula is more significant, and there is no reproductive toxicity.

OBJECTIVE To evaluate the efficacy and safety of Huoxue Xiaoyi Granule in inhibiting the recurrence of endometrio-sis(EMs)after conservative operation,and to provide evidence for Chinese medicine in inhibiting the recurrence of EMs.METHODS A total of 72 patients with qi-stagnation and blood-stasis after EMs operation were selected as the study objects and randomly divid-ed into the Chinese medicine group and the Western medicine group,36 cases in each group.The Chinese medicine group was treated with Huoxue Xiaoyi Granule,and the Western medicine group was treated with GnRH-α.The postoperative recurrence rate,TCM syn-drome score,carbohydrate antigen 125(CA125),dysmenorrhea score,pelvic pain score,pregnancy rate,serum sex hormones[estra-diol(E2),luteinizing hormone(LH),follicle stimulating hormone(FSH)]and safety indexes of the two groups were observed.RE-SULTS At 9 months and 12 months after surgery,the total TCM syndrome scores of the two groups of patients were significantly re-duced(P<0.05),and the Chinese medicine group was better than the Western medicine group(P<0.05);12 months later,the TCM total clinical curative rate in the Chinese medicine group was better than that in the Western medicine group;after surgery,the serum CA125 levels,dysmenorrhea scores and pelvic pain severity of the two groups of patients were significantly reduced(P<0.05,P<0.01);during treatment,the total incidence of adverse reactions in the Chinese medicine group was lower than that in the Western medicine group(P<0.01);the recurrence rate of the Chinese medicine group was slightly lower than that of the Western medicine group,but there was no statistical difference(P>0.05).CONCLUSION Huoxue Xiaoyi Granule can significantly improve TCM syndromes in patients with qi-stagnation and blood-stasis after EMs surgery.It is safe and has equivalent efficacy to GnRH-α in pre-venting postoperative recurrence of EMs,and worthy of clinical promotion and application.

ObjectiveTo explore the distribution and characteristics of traditional Chinese medicine （TCM） syndromes in patients with endometriosis （EMS）. MethodA cross-sectional survey was conducted to analyze the characteristics of TCM syndromes in 1 895 cases of EMS in hospitals of 19 provinces， autonomous regions， and municipalities. ResultAmong the 1 895 patients， Qistagnation and blood stasis syndrome accounted for the highest proportion， followed by Qi deficiency and blood stasis syndrome， cold coagulation and blood stasis syndrome， and kidney deficiency and blood stasis syndrome. The distribution of TCM syndrome types of patients with EMS in different regions， different treatment stages， and different disease types and with different therapeutic goals was different， and the differences were statistically significant. However， under different conditions， the Qi stagnation and blood stasis syndrome accounted for the highest proportion. Under the stratification of different regions， the cold coagulation and blood stasis syndrome in north China was relatively high， the kidney deficiency and blood stasis syndrome in south China was relatively high， and the combined phlegm and stasis syndrome was relatively high in southwest China. Different diagnosis and treatment goals corresponded to different clinical syndromes. With pelvic pain as the main manifestation， the proportion of cold coagulation and blood stasis syndrome was higher. The proportion of kidney deficiency and blood stasis syndrome was higher in married patients with infertility. Patients with the main diagnosis and treatment goals of controlling mass and inhibiting recurrence had a higher proportion of Qi deficiency and blood stasis syndrome. In different treatment stages， the proportion of Qi deficiency and blood stasis syndrome in postoperative patients and those with recurrent EMS was higher. Among different disease types， the Qi deficiency and blood stasis syndrome accounted for a higher proportion in patients with ovarian endometriosis （OEM）. The cold coagulation and blood stasis syndrome accounted for a higher proportion in patients with deep invasive endometriosis （DIE）. The kidney deficiency and blood stasis syndrome accounted for a higher proportion in patients with peritoneal EMS. There were significant differences in age， body mass index （BMI）， and course of disease among patients with different syndromes. Patients with Qi deficiency and blood stasis syndrome was relatively older， and their course of the disease was relatively long. Patients with combined phlegm and stasis syndrome had relatively high BMI. There was no significant difference in CA125 and CA199 levels among all syndrome types. ConclusionThe distribution of TCM syndromes of EMS has a certain regularity， and there are differences in regional distribution， therapeutic goals， treatment stages， and disease types（P<0.05）. However， the Qi stagnation and blood stasis syndrome accounts for a large proportion under different conditions， suggesting that Qi stagnation is the key link of EMS. In the early stage， the team took relieving depression and activating blood as the primary treatment， and created Huoxue Xiaoyi prescription， which was the core prescription for the treatment of EMS with Qi stagnation and blood stasis syndrome， achieving good clinical effect. At the same time， it is emphasized that EMS treatment should be integrated into the concept of chronic disease management and combined with health management. Through psychological counseling， cognitive behavior intervention， popular science lectures， and other methods， it is advised to adjust the emotion of patients with EMS， thereby increasing the curative effect. This study is expected to provide references for the clinical treatment of EMS.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC₅₀ > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

OBJECTIVE To s tudy the impr ovement effects of tilianin on the atherosclerosis （AS）model mice and its potential mechanism. METHODS Eight C 57BL/6J mice were taken as the normal group. Forty ApoE－/－ mice were randomly divided into model group ，tilianin low-dose ，medium-dose and high-dose groups [ 2.1，3.5，7.0 mg/（kg·d）] and simvastatin group [positive control drug ，3.5 mg/（kg·d）]，with 8 mice in each group. Normal group was given normal diet ，and other groups were given high-lipid diet to induce AS model. At the same time ，normal group and model group were given normal saline intragastrically ， administration groups were given relevant drug intragastrically ，once a day ，for 12 consecutive weeks. The levels of TC ，TG， LDL-C，HDL-C，Ox-LDL，IL-1β，IL-6，MCP-1 and TNF-α in plasma were determined. The pathomorphological changes of the aorta in mice were observed. The positive rate of ICAM- 1，VCAM-1 and PCNA in the aorta were determined. mRNA expressions of MMP- 2，MMP-9，TGF-β1，Smad2 and Smad 3 as well as protein expressions of TGF-β1，Smad2/3 and p-Smad 2/3 were also determined in aorta of mice. RESULTS Compared with normal group ，the plasma levels of TC ，TG，LDL-C，Ox-LDL，IL-1β， IL-6，MCP-1 and TNF-α in model group were increased significantly（P＜0.01），while HDL-C level was significantly reduced （P＜0.01）. Lipid plaques were formed in the aorta ，and the plaque area was large and caused severe stenosis of the lumen. mRNA expressions of MMP- 2，MMP-9，TGF-β1，Smad2 and Smad 3 as well as positive rate of ICAM- 1，VCAM-1，PCNA and protein expression TGF-β1，Smad2/3，and p-Smad 2/3 in the aorta were significantly increased （P＜0.01）. Compared with model group ， most of above indexes of medication groups were improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Tilianin can inhibit the activation of TGF-β1/Smads signaling pathway and then inhibit the proliferation of vascular smooth muscle cells ，reduce ， inflammation and regulate lipid metabolism to inhibit the No.81960766） formation of AS.

OBJECTIVE：To s tudy the effects of Dracocephalum moldavica total flavonoids （TFDM）on AMPK/SIRT 1/PGC-1α signaling pathway ，and to explore the mechanism of its protective effect on myocardial ischemia reperfusion injury （MIRI）rats. METHODS：Totally 50 healthy male SD rats were randomly divided into sham operation group ，model group ，TFDM group [ 60 mg/（kg·d），by extract] ，Compound C+TFDM group [ig administration of 60 mg/（kg·d）TFDM+intravenous injection of 250 μg/kg Compound C（AMPK inhibitor ）via tail vein 15 min before reperfusion] ，EX-527+TFDM group [ig administration of 60 mg/ （kg·d）TFDM+ip injection of 5 mg/kg EX- 527（SIRT1 inhibitor）20 min before reperfusion] ，with 10 rats in each group. They were given relevant medicine intragastrically ，once a day ，for consecutive 7 days. After last ig administration ，sham operation group underwent sham operation ，other 4 groups were established MIRI model by ligating left anterior descending coronary artery ， ischemia for 30 min and reperfusion for 2 h. After reperfusion ，the myocardial histopathological changes were observed by HE staining；RP-HPLC method was used to determine the contents of ATP ，ADP，AMP and NAD + in cardiac tissue. mRNA expressions of AMPK ，SIRT1 and PGC- 1α were detected by quantitative real-time PCR assay. Western blotting assay was the expressions of SIRT 1 and PGC- 1α protein in myocardium. RESULTS： Compared with sham operation group ， model group showed myocardial fib ers arranged disorder and horizontal stripes disappearance ，cell swelling burst and necrosis ，and nuclei deformation displacement ；the contents of ATP and NAD+，mRNA expression of AMPK ，SIRT1 and PGC- 1α，protein expression of SIRT 1 and PGC- 1α in cardiac tissue were decreased significantly （P＜0.05 or P＜0.01）；the contents of ADP and AMP ，the phosphorylation level of AMPK protein were increased significantly （P＜0.01）. Compared with model group ，myocardial pathological morphology were improved significantly in TFDM group ；the contents of ATP and NAD + in cardiac tissue ，mRNA expression of AMPK ，SIRT1 and PGC- 1α，the phosphorylation level of AMPK protein ，the protein expression of SIRT 1 and PGC- 1α were increased significantly（P＜0.05 or P＜ 0.01），while the contents of ADP and AMP were decreased significantly （P＜0.01）. Compared with TFDM group ，improvement effects of Compound C + TFDM group and EX- 527 + TFDM group on above indexes were reversed （P＜0.05 or P＜0.01）. CONCLUSIONS：TFDM may play a protective role on myocardium by activating AMPK/SIRT 1/PGC-1α signaling pathway and regulating energy metabolism.