Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

Objective: To compare the changes in the concentration of relevant growth factors released from platelet-rich plasma (PRP) stored at -80℃ by cryopreservation and at 4℃ by refrigerated lyophilization over 2 years, aiming to provide a theoretical basis for prolonging PRP storage duration. Methods: PRP (n=15) was separated using a blood cell separator and stored under -80℃ cryopreservation (F-PRP group) and 4℃ refrigerated freeze-drying conditions (FD-PRP group). The contents of growth factors (PDGF-AA, PDGF-BB, EGF, TGF-β1, and VEGF) in both groups were measured by ELISA at 1, 3, 6, 9, 12 and 24 months. Results: PDGF-AA and VEGF maintained good stability in both groups for up to 24 months. PDGF-BB and TGF-β1 showed high stability in the first 12 months but their stability decreased gradually from 12th to 24th months. EGF demonstrated good stability in the first 6 months, and its stability gradually decreased from the 9th to 24th months. Comparing the F-PRP and FD-PRP groups, the concentrations of the five growth factors in the FD-PRP group were either not statistically different or higher than those in the F-PRP group at all time points. Specifically, the concentrations of EGF were significantly higher in the FD-PRP group at all time points. Conclusion: Both -80℃ freezing and 4℃ freeze-drying enable long-term preservation of PRP. Freeze-drying imposes less stringent storage requirements and facilitates growth factor compared to frozen storage.

Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.

OBJECTIVE To investigate the intervention effect of kushenol F （KSC-F） on ulcerative colitis （UC） mice. METHODS Totally 30 male C57BL/6J mice were randomly divided into the normal group， model group， positive drug group （sulfasalazine， 703 mg/kg）， KSC-F 50 mg/kg group （KSC-F50 group）， and KSC-F 100 mg/kg group （KSC-F100 group）， with 6 mice in each group. Except for the normal group， the mice in the remaining groups were given 3% dextran sulfate sodium solution continuously for 7 days to induce UC model. Concurrently， administration groups received corresponding drug solution intragastrically， once a day， for 10 consecutive days. During the experiment， the changes in body weight and bowel movements of the mice were observed. Disease activity index scoring was performed after the last administration. The histopathological morphology of colonic tissue was examined. The levels of inflammatory factors in the serum and colon tissue were measured. Additionally， the mRNA expression of inflammatory factors， and the protein expressions of inflammation-related proteins [interleukin-1β （IL-1β）， forkhead box O1（FOXO1）， phosphoinositide 3-kinase（PI3K）， phosphorylated PI3K（p-PI3K）， p38 mitogen-activated protein kinase（p38 MAPK）， phosphorylated p38 MAPK（p-p38 MPAK） and phosphorylated protein kinase B（p- Akt）] were determined in colonic tissue. RESULTS KSC-F could alleviate weight loss and colonic tissue damage in UC mice. KSC- F reduced the levels of IL-1β， IL-6， IL-8 and tumor necrosis factor-α （TNF-α） in serum， as well as IL-1β， IL-6， IL-17 and TNF- α in colonic tissue to varying degrees and increased the levels of IL-10 in both serum and colonic tissue （P＜0.05 or P＜0.01）. Moreover， KSC-F decreased the expression levels of IL-1β， IL-17 and TNF-α mRNA， as well as p-PI3K， p-p38 MAPK， and p- Akt proteins in colonic tissue to varying degrees， and increased the expression levels of IL-10 mRNA and FOXO1 protein in colonic tissue （P＜0.05 or P＜0.01）. CONCLUSIONS KSC-F effectively alleviates UC symptoms in mice by inhibiting PI3K， Akt and p38 MAPK activation， mitigating the release of pro-inflammatory factors such as IL-1β， IL-6， TNF- α，promoting the anti-inflammatory factor IL-10 secretion， and reducing inflammation-induced colonic tissue damage.

Objective To assess the tear film stability and morphological characteristics of the tarsal gland in myopic children.Methods In this prospective descriptive study,myopic children who performed refractive examinations in the Pediatric Ophthalmology & Refraction Clinic,Jinan Mingshui Eye Hospital from November 2021 to November 2022 were in-cluded.An Ocular Surface Disease Index(OSDI)questionnaire survey was carried out;tear meniscus height(TMH),non-invasive first breakup time(NIf-BUT)and images of the tarsal glands were obtained by OCULUS Keratograph 5M compre-hensive ocular surface analyzer.In addition,the atrophy and tortuosity of tarsal glands were scored to analyze the tear film stability and clinical characteristics of tarsal glands in myopic children.Results A total of 48 myopic children(91 eyes)aged from 7 to 16(10.25±2.23)years were recruited,including 27 males(56.25％)and 21 females(43.75％).The aver-age TMH was(0.19±0.04)mm(95％CI:0.18-0.19)and the average NIf-BUT was(5.40±2.62)s(95％CI:4.90-5.94);the TMH was positively correlated with NIf-BUT(r=0.223,P=0.034).The tarsal gland atrophy score was 1(0,1).The tortuosity score of the upper and lower tarsal gland was 0(0,1)and 0(0,0),respectively,with a statistically significant difference(Z=3.692,P＜0.001).In all subjects,49 eyes(53.85％)had tarsal gland atrophy,and 37 eyes(40.66％)had tarsal gland tortuosity.There were significant differences in TMH and NIf-BUT between children aged＜12 years and children aged ≥12 years(both P＜0.05).There was a significant difference in TMH between children with an OSDI score＜13 and children with an OSDI score ≥ 13(t=2.305,P=0.026).There was a significant difference in NIf-BUT between mild and moderate myopia children(t=2.300,P=0.024);the spherical equivalent was positively correlated with NIf-BUT(r=0.283,P=0.023).Conclusion Children with mild to moderate myopia show low tear film stability and a certain proportion of abnormal morphology in tarsal glands.In addition to the refractive status of children,attention should also be paid to ocular surface health in the refraction clinic.

ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg^-1） and Captopril group （0.002 57 g·kg^-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

ObjectiveTo investigate the incidence of hypertension and its influencing factors in community-dwellers at risk for high blood pressure in Minhang District of Shanghai， and to provide scientific evidence for the community management. MethodsA retrospective cohort study was conducted using the electronic health records of community-dwellers at risk for high blood pressure in Minhang District， Shanghai from January 1， 2011 to December 31， 2017. The study end-point was the occurrence of hypertension，and the followup was finished in December 2021. A total of 17 265 community-dwellers at risk for high blood pressure were enrolled in our study. Log-rank test and Cox regression analysis were used to determine the influencing factors. ResultsAfter 6.04 years of follow-up， the hypertension incidence among community-dwellers at risk for high blood pressure in Minhang District of Shanghai was 25.5%. Family history of hypertension （HR=1.250， 95%CI： 1.168‒1.338）， family history of stroke （HR=1.295， 95%CI： 1.080‒1.553）， history of diabetes （HR=1.203， 95%CI： 1.076‒1.345）， daily smoking （HR=1.187， 95%CI： 1.087‒1.296）， overweight （HR=1.393， 95%CI：1.308‒1.484）， obesity（HR=1.903， 95%CI： 1.719‒2.106）， high values of normal blood pressure （HR=1.275， 95%CI： 1.195‒1.359） and advanced age （HR=1.033， 95%CI： 1.030‒1.036） were all risk factors. Emaciation （HR=0.649， 95%CI： 0.500‒0.840） was a protective factors. ConclusionBlood pressure monitoring should be strengthened for people elderly， with family history of hypertension， family history of stroke， diabetes or high values of normal blood pressure， so as to diagnose hypertension early. Timely intervention measures should be taken for community-dwellers with unhealthy lifestyles such as smoking， overweight and obesity.

BACKGROUND:Pulsed electromagnetic fields,as an important physical therapy,are exactly effective in the treatment of osteoarthritis,but the mechanism has not been fully clarified. OBJECTIVE:To observe the effect of pulsed electromagnetic field on the degeneration of knee joint cartilage in aged rats. METHODS:Eight 6-month-old Sprague-Dawley rats were selected as the young group and were subjected to normal diet with no treatment.Sixteen 22-month-old Sprague-Dawley rats were randomly divided into old group(n=8)and pulsed electromagnetic field group(n=8).The rats in the pulsed electromagnetic field group were subjected to a pulsed electromagnetic field intervention,once a day,5 days per week for continuous 8 weeks.The rats in the old group were given no treatment.All rats were anesthetized and executed after 8 weeks for the detection of relevant indexes. RESULTS AND CONCLUSION:Compared with the young group,serum type Ⅱ collagen C-terminal peptide level was increased in the old group(P<0.05);compared with the old group,serum type Ⅱ collagen C-terminal peptide level was decreased in the pulsed electromagnetic field group(P<0.05).Micro-CT showed that the bone volume fraction,bone mineral density,and number of bone trabeculae decreased(P<0.05)and the trabecular separation increased(P<0.05)in the tibia of rats in the aged group compared with the young group;and the bone volume fraction,bone density,and number of trabeculae increased(P<0.05)and the trabecular separation decreased(P<0.05)in the tibia of rats in the pulsed electromagnetic field group compared with the aged group.The tibial plateau Safranin O-fast green staining showed that the articular cartilage structure of rats in the aged group was disorganized,and the number of chondrocytes was obviously reduced,and the tidal line could not be distinguished.The above results were improved in the pulsed electromagnetic field group.RT-qPCR and western blot assay showed that the mRNA and protein expression levels of matrix metalloproteinase 1,matrix metalloproteinase 13,P53 and P21 in the articular cartilage and subchondral bone of rats were elevated in the aged group compared with the young group(P<0.05)and decreased in the pulsed electromagnetic field group compared with the old group(P<0.05).To conclude,pulsed electromagnetic fields may improve osteoarthritis in aged rats by inhibiting chondrocyte senescence,alleviating articular cartilage degradation and inhibiting subchondral bone osteoporosis through suppressing the expression of P53/P21.

Background The threshold limit values (TLVs) established and regularly updated by the American Conference of Governmental Industrial Hygienists (ACGIH) are widely adopted and referenced globally, serving as a crucial reference for China's occupational exposure limits (OELs). It is necessary to track it regularly and compare it with China's OELs. Objective To compare the OELs stipulated in Occupational exposure limits for hazardous agents in the workplace—Part 1: Chemical hazardous agents (GBZ 2.1—2019) and the ACGIH TLVs (2024) and to provide references for subsequent formulation and revision of OELs in China. Methods The OELs specified in GBZ 2.1—2019 and the TLVs issued by ACGIH were used to establish a database using Microsoft Excel 2019 software. Cross verification was conducted through matching Chemical Abstracts Service Registry Numbers (CAS Rn) and both Chinese and English names to ensure accuracy. Then, comparisons and analyses were carried out based on the type of limit values, which were matched as follows: permissible concentration-time weighted average (PC-TWA) with threshold limit value-time weighted average (TLV-TWA), permissible concentration-short term exposure limit (PC-STEL) with threshold limit value-short term exposure limit (TLV-STEL), and maximum allowable concentration (MAC) with threshold limit value-ceiling (TLV-C). Comparisons included types, quantities, and sizes of limits. Results The GBZ 2.1—2019 OELs and the ACGIH TLVs (2024) were generally consistent in terms of types and definitions, but there were differences in the number and size of the limits. In terms of the number of limits, GBZ 2.1—2019 specified 365 OELs for 358 chemical hazardous agents, while ACGIH TLVs (2024) included 316 corresponding limits. Among these, 148 (46.9%) limits were consistent, 38 (12.0%) were basically consistent, and 130 (41.1%) were inconsistent. In terms of the size of the limits, out of the 130 inconsistent limits, 51 OELs were lower than the corresponding TLVs, 67 OELs were higher than the corresponding TLVs, and 12 were under different limit types. For some chemical hazardous agents, their OELs were significantly lower or higher than their TLVs. Conclusion Some of the OELs for chemical hazardous agents specified in GBZ 2.1—2019 are significantly lower or higher than the TLVs. For these chemical hazardous factors, it is recommended to prioritize their inclusion in research projects and to complete the revisions as soon as possible based on the latest scientific evidence.