ObjectiveTo explore the therapeutic mechanism of Buchong Tiaojing prescription for rats with diminished ovarian reserve （DOR） from the perspectives of nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） inflammasome and ferroptosis. MethodsA total of 48 female SD rats were randomly divided into a normal group， a model group， low， medium， and high dose groups of Buchong Tiaojing prescription， and an MCC950 group， with eight rats in each group. Except the normal group， all the other groups were injected subcutaneously on the back of the neck with D-galactose to prepare the DOR rat model. From the 15th day of modeling， the rats in the low， medium， and high dose groups of Buchong Tiaojing prescription were subjected to gavage daily at doses of 14.4， 28.8， 57.6 g·kg^-1， respectively. Rats in the MCC950 group were injected intraperitoneally with MCC950 at a dose of 10 mg·kg^-1， once every other day. The interventions of all the groups lasted for 4 weeks. The estrous cycle of the rats was observed with vaginal exfoliated cell smear. Hematoxylin-eosin （HE） staining was performed to observe the development of follicles and corpus luteum in the ovary. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the levels of serum sex hormones and interleukin-1β （IL-1β）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot assay were performed to detect the mRNA and protein expression of NLRP3 inflammasome， acyl-CoA synthetase long-chain family member 4 （ACSL4）， transferrin receptor 1 （TFR1）， and glutathione peroxidase 4 （GPX4）， and oxidative stress kits were used to detect ovarian superoxide dismutase （SOD） and malondialdehyde （MDA） levels. ResultsDuring the experiment， one rat died in the high dose group of Buchong Tiaojing prescription， and a total of 47 rats were finally included in the index tests and statistics. Compared with those in the normal group， rats in the model group had significantly disturbed estrous cycles， increased number of atretic follicles， and significant disorder of serum sex hormones. The mRNA and protein expression of NLRP3 inflammasome， ACSL4， and TFR1 in ovarian tissue was up-regulated （P<0.01）， while that of GPX4 was significantly down-regulated （P<0.01）. The SOD content in the ovary was decreased significantly， while the MDA level was increased （P<0.01）. After drug intervention， the estrous cycle of rats was basically resumed， and the follicles at all levels were more structurally intact and significantly increased in number. Additionally， the levels of serum sex hormones and IL-1β were significantly improved. The mRNA and protein expression of NLRP3 inflammasome， ACSL4， and TFR1 were down-regulated， while that of GPX4 was significantly up-regulated， and the ovarian oxidative stress was alleviated （P<0.05， P<0.01）， especially in the high dose group of Buchong Tiaojing prescription and the MCC950 group. ConclusionInflammatory injury and ferroptosis occur in the ovaries of DOR rats， and the Buchong Tiaojing prescription is able to inhibit ovarian NLRP3 inflammasome， alleviate the degree of ovarian ferroptosis， and improve ovarian reserve.

ObjectiveTo observe and compare the electrocardiogram index， myocardial morphology， and connexin 43 （Cx43） expression of two rat models of acute cerebral infarction （ACI） due to stasis combined with toxin complicated with cerebral-cardiac syndrome （CCS）， and to provide experimental evidence for the research on the occurrence mechanism of cardiac diseases induced by ACI and the clinical diagnosis and treatment of CCS. MethodSixty SPF-grade male SD rats were randomized into six groups （n=10）： normal ， syndrome of stasis combined with toxin induced by carrageenin combined with dry yeast （CA/Y）， multi-infarct induced by micro-embolism （ME）， middle cerebral artery occlusion （MCAO）， CA/Y+ME， and CA/Y+MCAO groups. The model of syndrome of stasis combined with toxin was established by intraperitoneal injection with carrageenan （CA） at 10 mg·kg^-1 on the first day and subcutaneous injection with dry yeast （Y） suspension （2 mg·kg^-1） on the second day of modeling. Twenty-four hours after the modeling of ACI， the electrocardiograms （ECGs） of rats in each group were collected and the number/percentage （%） of abnormal ECG was calculated. The infarct area of the brain was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and myocardial injury was assessed by hematoxylin-eosin （HE） staining. Immumohistochemical staining and Western blot were employed to determine the expression of Cx43 in the myocardium. ResultA certain number of rats in each model group presented abnormal ECG. Compared with the normal group and CA/Y group， CA/Y+MCAO group had the highest rate of abnormal ECG （P<0.01）. Compared with the normal， CA/Y， ME， and CA/Y+ME groups， the CA/Y+ME and CA/Y+MCAO groups showed decreased amplitudes of P-wave and T-wave， shortened P-R interval， and extended Q-T interval， which were particularly obvious in the CA/Y+MCAO group （P<0.05， P<0.01） and in accordance with the cerebral infarction area and pathological changes. The expression of Cx43 was up-regulated in both CA/Y+ME and CA/Y+MCAO groups， especially in the CA/Y+MCAO group （P<0.01）. ConclusionThe two rat models of ACI due to stasis combined with toxin complicated with CCS can be used to study the mechanism of heart diseases caused by cerebrovascular diseases and the therapeutic effects of Chinese medicines with the functions of resolving stasis and detoxifying. Moreover， the CA/Y+MCAO method has higher abnormal electrocardiogram rate， severer myocardial pathological injury， and higher expression of Cx43 protein. The models can be chosen according to specific experimental purpose.

Objective To investigate the correlation between brain injury and spleen damage in a rat model of acute ischemic stroke and stasis interaction,and its effect on the MCP-1/CCR2 axis,and to provide an experimental basis for the mechanism of brain-spleen inflammatory coupling in spleen lesions caused by acute ischemic stroke.Methods Forty male SD rats were randomly divided into a sham group,carrageenan/yeast stasis syndrome group(carrageenan/yeast,CA/Y),middle cerebral artery occlusion group(MCAO),and middle cerebral artery stasis syndrome group(MCAO CA/Y)with 10 rats in each group.CA/Y and MCAO CA/Y groups were injected with 10 mg/kg carrageenan and 10 mg/kg intraperitoneally on the first day of modeling.2 mg/kg of dry yeast suspension were injected subcutaneously on the second day.MCAO and MCAO CA/Y groups were established by wire embolism on the second day.At 24 h after cerebral infarction modeling,the neurological deficit score was calculated in each group,the percentage of the cerebral infarction area was determined by TTC staining,the spleen weight was measured,and the correlation between the percentage of the cerebral infarction area and spleen weight was analyzed by the Spearman correlation coefficient.Furthermore,the pathological morphology of brain and spleen tissues was observed by hematoxylin-eosin(HE)staining,and chemotactic protein 1(MCP-1)and interferon-γ(IFN-γ)contents were measured in rat plasma by enzyme-linked immunosorbent assays.Western blot was used to detect chemokine C-C-motif receptor 2(CCR2)protein expression in the ischemic side of brain tissue.Results Compared with the sham group,the neurological deficit score,cerebral infarction area,and MCP-1 and IFN-γ contents in plasma were significantly increased(P＜0.01),spleen weight was decreased significantly(P＜0.01),and CCR2 protein expression in brain tissue was significantly upregulated(P＜0.05)in MCAO and MCAO CA/Y groups.Moreover,the area of cerebral infarction was increased significantly(P＜0.01),the spleen weight was decreased significantly(P＜0.01),and CCR2 protein expression in brain and spleen tissues was significantly upregulated(P＜0.05)Compared with the MCAO group,the area of cerebral infarction in the MCAO CA/Y group was significantly increased(P＜0.01)and the spleen weight was decreased significantly(P＜0.05).Spearman correlation analysis showed that the spleen weight was negatively correlated to the percentage of the cerebral infarction area(P＜0.01,r=-0.9711).Pathological morphology observation revealed that the pathological changes in the MCAO CA/Y group were the most serious,cerebral liquefaction necrosis foci were seen in the brain tissue cortex,arrangement of neuronal cells in the lesions was sparse and disordered with volume atrophy and a small number of vacuoles and nuclear solidification,most neuronal cells were degenerated and necrotic,microglia hyperplasia was obvious,small blood vessels were significantly increased,and interstitial lipid degeneration was severe.The density of periarterial lymph sheath cells in some of the spleen tissue was reduced and the marginal area is widened.Conclusions A correlation between brain and spleen injury was found after acute ischemic stroke with stasis and toxin syndrome,and the chemokine signaling axis of MCP-1/CCR2 might be involved in the mechanism of brain-spleen inflammation coupling.

Objective:To construct a fall risk prediction model for patients with hematologic malignancies and to provide a reference for the risk assessment and accurate management of falls.Methods:The prospective study design was adopted to facilitate the selection of 510 patients with hematologic malignant in Qilu Hospital of Shandong University for investigation, and relevant data such as patient demographic characteristics, disease treatment and drugs were collected. The LASSO-Logistic regression was used to screen the risk factors of falls in patients with hematologic malignancies, to construct a nomogram risk prediction model. The receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the predictive performance of the model. Bootstrap resampling were used to validate internal validation of the model.Results:Among 510 patients with hematological malignancies, there were 273 males and 237 females, aged 53.0 (41.0, 63.0) years old. A total of 6 risk factors were included in the fall risk prediction model for patients with hematological malignancies, which were disease type ( OR = 0.185, 95% CI 0.061 - 0.562), body temperature ≥38 ℃ ( OR = 2.239, 95% CI 1.128 - 4.445), pain ( OR = 15.581, 95% CI 6.592 - 36.829), anemia ( OR = 4.097, 95% CI 1.536 - 10.927), days of bone marrow suppression ( OR = 3.341, 95% CI 1.619 - 6.893), and assessment of daily self-care ability ( OR = 3.160, 95% CI 1.051 - 9.506)(all P<0.05). The ROC curve of the fall risk prediction model was 0.884 (95% CI 0.841-0.927). The optimal threshold, sensitivity, and specificity of the risk prediction model were 0.248, 87.4% and 75.6%. The internal validation C statistic was 0.873. The Calibration curve was almost coincides with the ideal curve, and the model Brier score was 0.080. Conclusions:The constructed fall risk prediction model has good predictive performance, which can efficiently and objectively quantify the risk of falls, and provide a reference for the early assessment and effective prevention of falls in patients with hematological malignancies.

Objective To evaluate the feasibility,reliability and validity of the symptom identification scale for kidney yang deficiency syndrome.Methods The symptom identification scale for kidney yang deficiency syndrome developed in previous research was administered to 200 vascular cognitive impairment patients from September 2020 to September 2022 to assess feasibility through recall rate,completion rate,and completion time;reliability was measured using retest reliability,split-half reliability,homogeneity reliability,and inter-rater reliability;and validity was evaluated based on discriminant and structural validity.Results A total of 200 scales were sent out,and all of them cooperated and were completed and retrieved within 20 min.The results of reliability analysis showed that the retest reliability of the scale was 0.828 for the dimension of yang deficiency and 0.718 for the dimension of kidney qi deficiency;the Spearman-Brown coefficient of split-half reliability was 0.784;the Cronbach coefficient of the dimension of yang deficiency was 0.799,and the Cronbach coefficient of the dimension of kidney qi deficiency in the homogeneity reliability was 0.670.The results of the analysis showed that the differences between the kidney yang deficiency syndrome group and the non-kidney yang deficiency syndrome group in the yang deficiency dimension,kidney qi deficiency dimension scores and total scale scores in the discriminant validity were statistically significant(P<0.001);the KMO value in the structural validity was 0.842,and a total of two factors with eigenvalues greater than 1 were extracted,with a cumulative variance contribution rate of 58.227%.Conclusion The symptom identification scale for kidney yang deficiency syndrome demonstrates adequate reliability and validity,potentially enhancing the prediction of kidney yang deficiency in vascular cognitive impairment.However,the validity of the scale is somewhat limited and requires further refinement for clinical application.

Objective To investigate the effect of probiotics in patients with chronic heart failure (CHF) and its impact on intestinal microecology. Methods A total of 112 patients with CHF were selected as research subjects and randomly divided into study group and control group, with 56 patients in each group. The control group received angiotensin-converting enzyme inhibitors (ACEI) combined with angiotensin Ⅱ receptor blockers (ARB) for treatment, while the study group received bifidobacterium viable capsules on the basis of treatment in the control group. The levels of myocardial fibrosis markers[type Ⅰ collagen precursor C-propeptide (PⅠCP), type Ⅲ collagen precursor N-propeptide (PⅢNP), PⅠCP/PⅢNP, type Ⅰ collagen carboxyl-terminal peptide (ⅠCTP)], cardiac function indicators[leftventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic volume (LVESV)], intestinal flora abundance, plasma trimethylamine oxide (TMAO) levels, and serum tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) levels were measured in both groups. The therapeutic effects, drug safety, re-hospitalization rate, and mortality rate within 3 months after discharge were observed in both groups. Results The total effective rate in the study group was 71.43 %, which was higher than 51.79 % in the control group (P < 0.05). After treatment, the LVEF in the study group was higher than that in the control group, while LVEDD, LVESD, and LVESV were lower than those in the control group (P < 0.05). After treatment, the PⅠCP/PⅢNP in the study group was higher than that in the control group, while the ⅠCTP level was lower than that in the control group (P < 0.05). After treatment, the abundances of Proteobacteria, Actinobacteria, Firmicutes, and Fusobacteria in the study group were lower than those in the control group, while the abundance of Bacteroidetes was higher than that in the control group (P < 0.05). After treatment, the levels of TMAO, TNF-α, and IL-1β in the study group were lower than those in the control group (P < 0.05). No serious adverse reactions occurred in either group after treatment. Within 3 months after discharge, the re-hospitalization rate in the study group was 12.50 %, which was lower than 30.36 %in the control group (P < 0.05). The mortality rates in the study group and the control group were 1.79 % and 7.14 %, respectively, but no statistically significant difference was observed(P>0.05). Conclusion The combination of probiotics with ACEI and ARB can effectively reduce myocardial fibrosis in patients with CHF and improve intestinal microecology and prognosis.

Objective:To explore the influencing factors and effectiveness of community follow-up in patients with cardiac implantable electronic device (CIED) implantation.Method:A total of 132 patients who received CIED implantation in the Department of Cardiology of Tongren Hospital, Shanghai Jiao Tong University School of Medicine from February 2021 to February 2022 were enrolled in this prospective cohort study. Among them 33 patients were followed up in community health service centers associated with Tongren Hospital (community follow-up group) and 99 matched patients were followed up in the CIED outpatient clinic of the hospital (outpatient follow-up group) with a ratio of 1∶3. The clinical data of the selected patients were collected through a questionnaire survey; the follow-up data were extracted through the CarelinkExpress electronic follow-up platform and the CIED outpatient information system of Tongren Hospital. Adjustment of the treatment protocol or CIED parameters at follow-up, and the referral from the community health service centers were defined as visit with-an-action (VWA). The endpoint of follow-up was the occurrence of major adverse events. The multivariate logistic regression model was used to analyze the factors influencing patient selection for community follow-up.Results:The univariate analysis showed that the frequency of visits to community health service centers and the service contracting rate in community follow-up group were higher than those of outpatient follow-up group ( P<0.05). The multivariate logistic regression analysis showed that the contracted community physician service was an independent influencing factor of patient choosing community follow-up ( OR=2.143, 95% CI: 1.103-4.166, P=0.025). A total of 469 visits of followed up occurred in 132 patients, including 45 community visits and 424 outpatient visits. VWA accounted for 22.2% (10/45) in the community follow-up group, and 17.2% (73/424) in the outpatient follow-up group ( P>0.05). There was no significant difference in the safety and effectiveness indicators (VWA, major adverse events, and unplanned follow-up) between the two groups ( P>0.05). More patients in the community follow-up group walked to the hospital than the outpatient follow-up group ( P<0.05);and the main transportation for the later was by bus or taxi(42(42.4%)or 41(41.4%)). The average waiting time in the community follow-up group was significantly shorter than that in outpatient follow-up group ( P<0.05). The total time required for a single follow-up in the community follow-up group was 50.0 (45.0, 59.5) minutes, which was significantly shorter than that in the routine outpatient follow-up group (107.0 (90.0, 135.0) minutes, P<0.05). Conclusions:The contracting with community physicians is an independent influencing factor for CIED implanted patients to choose community follow-up. The safety and effectiveness of community follow-up are comparable to routine outpatient follow-up, and community follow-up is more convenient.

Objective : To explore the effect of hydroxy⁃carboxylic acid receptor 2 (HCAR2) on erythroid differen⁃ tiation of human chronic myeloid leukemia K562 cells under hypoxia . Methods : The cells were cultured in medium containing hemin to compare the ability of K562 cells to differentiate into erythroid cells under normoxia/hypoxia conditions . Then the expression of HCAR2 was interfered with genetic methods to knockdown or overexpress it in K562 cells , respectively . Benzidine staining , RT⁃qPCR , Western blot and flow cytometry were used to detect the role of HCAR2 in the erythroid differentiation of K562 promoted by hypoxia . Results : On day 1 , 2 , 3 after differentiation , the expression level of HCAR2 and the erythroid differentiation， the expression level of HCAR2 and the erythroid differentiation ability of K562 cells increased gradually with time , and hypoxia enhanced the above phenotypes compared with normoxia . In HCAR2⁃silenced K562 cells , erythroid cells was reduced and the expression of erythroid differentiation markers CD235a and γ⁃globin decreased . Simultaneously , the proportion of double⁃positive cells expressing erythroid cell surface molecules CD71 and CD235a was lower than that of the control group . On the contrary , the overexpression of HCAR2 in K562 cells increased erythroid cells generation as well as elevated the expression levels of CD235a and γ⁃globin . In addition , the proportion of CD71 /CD235a double⁃positive cells also increased in HCAR2⁃overexpressed K562 cells . Conclusion HCAR2 mediates hypoxia in promoting the erythroid differentiation of K562 cells .

Abstract Allostatic load (AL) is related to stress. Adverse childhood experiences(ACEs), as a common stress in childhood, can make a serious and lasting impact on it. Allostatic load can reflect the wear and tear of an individual s physiological system. This article mainly reviews the functional changes of several systems of AL who have experienced ACEs, including neuroendocrine, metabolism, immune, and cardiovascular systems, as well as the different effects of the occurrence time and subtypes of ACES on AL, providing some theoretical basis for the development of early intervention plans in the future and reducing the occurrence and development of deleterious outcomes.

Objective:To investigate the influence of abnormal blood pressure circadian rhythms and the morning surge on aortic stiffness in elderly patients with isolated systolic hypertension(ISH).Methods:A total of 300 untreated elderly(≥60 years)patients with ISH were enrolled.24-hour ambulatory blood pressure was measured by using a non-invasive portable ambulatory sphygmomanometer with an inflatable cuff.Brachial-ankle pulse wave velocity(baPWV)and the ankle-brachial pressure index(ABI)were measured by using an automated device.Patients were divided into the dipper(n=95), no-dipper(n=177)and extreme dipper(n=28)groups according to the rate of nocturnal blood pressure reduction.They were also divided into the morning surge(n=88)and no morning surge(n=212)groups according to the morning blood pressure surge(MBPS). Differences between the groups were compared.Correlations between the parameters were calculated by partial correlation analyses.The effects on baPWV and ABI were calculated by multiple linear regression analyses.Results:baPWV was higher in the extreme dipper group than in the dipper and no dipper groups[(1 402±234)cm/s vs.(1 467±114)cm/s vs.(1 538±140)cm/s, P<0.01], while ABI values were lower in the extreme dipper group than in the dipper group(0.98±0.10 vs.1.05±0.12, P<0.01)and the no dipper group(0.98±0.10 vs.1.03±0.12, P<0.05). Moreover, baPWV[(1 508±170)cm/s vs.(1 430±163)cm/s, P<0.01]was higher while ABI values(0.98±0.13 vs.1.06±0.11, P<0.01)were lower in the morning surge group than in the no morning surge group.baPWV was positively correlated with daytime Systolic blood pressure(dSBP)( r=0.169, P<0.01), 24 hSBPCV( r=0.143, P<0.05), and MBPS( r=0.157, P<0.01), while ABI was negatively correlated with dSBP( r=-0.146, P=0.011)and MBPS( r=-0.321, P<0.01). Age( P<0.01), dSBP( P<0.05)and 24 h systolic blood pressure variation coefficient( P<0.05)were independent factors for baPWV, while dSBP and MBPS were independent factors for ABI(all P<0.01). Conclusions:Abnormal blood pressure circadian rhythms and the morning surge are associated with increased aortic stiffness in elderly patients with ISH.