BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

BACKGROUND:Fluid shear stress plays an important role in osteoblast proliferation and apoptosis.However,whether Caveolin-1 is involved in the process of fluid shear stress-induced proliferation and apoptosis in osteoblasts is unknown. OBJECTIVE:To explore the role of Caveolin-1 in fluid shear stress-regulated osteoblast proliferation and apoptosis. METHODS:The MC3T3-E1 osteoblasts in good growth status were selected and loaded with fluid shear stress at an intensity of 1.2 Pa for different times(0,30,60,90 minutes).The expression of Caveolin-1 protein was observed and conditions with a time of 60 minutes were screened for the experiment.MC3T3-E1 cells were divided into control group,fluid shear stress group,fluid shear stress+pcDNA 3.1 group(control),fluid shear stress+pcDNA Cav-1 group(plasmid overexpression),and intervened with fluid shear stress and overexpression of Cav-1,respectively.The expression of molecules related to proliferation and apoptosis in MC3T3-E1 cells was detected by qRT-PCR and western blot.In addition,the proliferative activity of MC3T3-E1 cells was detected by cell counting kit-8 and EdU assay;and cell apoptosis was detected by Hoechst 33258 and flow cytometry. RESULTS AND CONCLUSION:The expression of Caveolin-1 in MC3T3-E1 cells was significantly down-regulated after loading fluid shear stress,and the expression level was lowest after 60 minutes.Overexpression of Caveolin-1 attenuated the proliferation-promoting and apoptosis-suppressing effects of fluid shear stress in MC3T3-E1 cells.In conclusion,Caveolin-1 has a vital role in fluid shear stress-regulated osteoblast proliferation and apoptosis,which may offer a potential therapeutic strategy for osteoporosis.

Objective:To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC).Methods:The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan–Meier method was used for survival analysis.Results:We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4–112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2–21.8) months.Conclusion:The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.

Objective:To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC).Methods:The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan–Meier method was used for survival analysis.Results:We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4–112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2–21.8) months.Conclusion:The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.

Objective:To investigate the correlation between non-traditional lipid parameters and in-hospital recurrence in patients with acute minor ischemic stroke (AMIS).Methods:Patients with AMIS admitted to three sub-central hospitals in Shanxi Province within 72 h of onset in March, June, September, and December of 2012, 2014, 2016, and 2018 were retrospectively included. The demographic information, clinical features, blood lipid parameters, and in-hospital stroke recurrence events were collected. Non-traditional lipid parameters included low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio, total cholesterol (TC)/HDL-C ratio, triglycerides (TG)/HDL-C ratio, and non-HDL-C levels. Multivariate logistic regression analysis was used to determine the independent correlation between the non-traditional lipid parameters and the risk of in-hospitals stroke recurrence. Results:A total of 1 040 patients with AMIS were included, including 727 males (69.9%), aged 61.5±13.0 years old; 51 patients (4.904%) experienced in-hospital stroke recurrence, with an average time from admission to recurrence was 7.4±5.7 d. Four hundred and thirty-six (41.9%) AMIS patients complicated with ICAS, aged 61.0±12.5 years old, with 304 males (69.7%); 26 (6.0%) experienced recurrence of in-hospital stroke, and the time from admission to recurrence was 7.8±6.2 d. Multivariate logistic analysis showed that after adjusting for confounding variables, the higher TC/HDL-C ratio (odds ratio [ OR] 1.35, 95% confidence interval [ CI] 1.02-1.77; P=0.035) and non-HDL-C ( OR 1.37, 95% CI 1.02-1.77; P=0.045) were the independent risk factors for in-hospital stroke recurrence. In AMIS patients with intracranial atherosclerotic stenosis, only higher non-HDL-C was significantly and independently associated with the risk of in-hospital stroke recurrence ( OR 1.67, 95% CI 1.05-2.65; P=0.030). Conclusion:The higher non-traditional lipid parameters are associated with an increased risk of in-hospital stroke recurrence in patients with AMIS.

The main function of anterior cruciate ligament (ACL) is to maintain stability of the knee joint and prevent anterior displacement of the tibial plateau. ACL injury accounts for more than 50% of the knee joint injuries. If not timely handled, it will increase the risk of secondary injuries to structures such as the meniscus and cartilage, causing chronic pain and degeneration of the knee joint. Although most ACL injuries can be determined by their direct signs on MRI, the identification of complex situations and partial tears of ACL are still not satisfactory, which subsequently affects treatment strategies. After ACL injury, changes in anatomical relationship of the knee joint can also lead to morphological changes in other structures such as the posterior cruciate ligament (PCL) on MRI, and these indirect signs can assist in the diagnosis of ACL injury. The authors reviewed the application of MRI-related indicators of PCL in diagnosing ACL injury, hoping to provide references and new ideas for clinical decision-making.

Objective To design an interactive and shared electronic database for long-term follow-up management of patients with acute minor stroke (NIHSS≤5) using REDCap,and to explore the value of establishing this database,trying to provide new ideas for clinical treatment. Methods The CRF table of case report was designed according to the relevant data of patients in hospital and the requirements of follow-up management. The nosocomial case data of patients with acute minor stroke (NIHSS≤5) from 3 stroke centers in Shanxi Province were collected and recorded on the CRF form of case reports. An interactive shared electronic database was designed by REDCap,and the data in CRF table were checked and revised and entered into the database. Patients were followed up at 3 months and 1 year after onset. Results Based on REDCap system,a database of acute minor stroke ( NIHSS≤5) in Shanxi Province was established and used in clinical practice. The number of patients expected to be included has been achieved. Its data entry,data quality control,user rights management and data export functions can be stable operation. Conclusion The interactive sharing clinical database of acute minor stroke ( NIHSS≤5) is established by redcap,which has the advantages of simple interface operation,convenient communication,timely entry,and multi-access. It provides a powerful tool for longitudinal data collection,reducing deviation in research,and comprehensively implementing and coordinating project research. It ensures the reliability of research results and has clinical research value.

Health service is an important part of the integrated development of the Yangtze River Delta. Taking the cooperation practice between Shanghai Tenth People′s Hospital and Suzhou Yinshanhu Hospital as an example, this article introduced the multi-agent cooperation mode of the loose medical alliance including the government, urban hospitals and cross provincial grassroots medical institutions. Among them, the local government provided policy, fund guarantee and guidance, the urban hospital exported management ideas, medicine talents and technologies, and the primary hospital conducted dual training by inviting in and going out to achieve double growth. Through the high gap cooperation between tertiary hospital and primary hospital, Yinshanhu hospital had been comprehensively developed. The loose medical alliance with multi subject coordination and cross region could give full play to the advantages of the loose healthcare alliance mode, achieve multi-win, and have reference significance for promoting the regional integration of medical and health services in the Yangtze River Delta.

Objective: To study the effects of resistant dextrin (RD) on liver fat deposition in high-fat diet-fed (HFD) mice, and to further explore whether it can regulate the AMPK signaling pathway. Methods: Thirty-six 4-week-old male C57BL/6 mice were randomly divided into three groups: normal control group (chow), high-fat diet group (HFD), and high-fat diet+ resistant dextrin group (HFD+ RD, 10 g·kg^-1·d^-1). After 12 weeks of intervention, the liver tissues and serum samples were collected. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), aspartate aminotransferase (AST), alanine transaminase (ALT) levels and liver TG were measured. Liver tissue HE and oil red O staining were performed to observe hepatocyte steatosis and liver fat deposition. Quantitative real-time PCR was performed to detect the relative expression of fatty acid synthesis related genes SREBP1, ACC, SCD1 in the liver tissue, and Western blot was performed to detect relative protein levels of pAMPK, SREBP1, Fasn, and ACC in the liver. Results: Compared with chow group, the body weight gain, fasting blood glucose (FBG), serum TC, LDL-C, HDL-C, and ALT levels were increased in HFD group (P<0.01), and serum AST level was also increased (P<0.05). Moreover, liver oil red O staining revealed that liver fat deposition was much more obvious in HFD group than that in chow group, and liver TG was also increased in HFD group (P<0.01). The mRNA levels of SREBP1 and ACC were increased in HFD group compared with that in chow group, and the protein level of pAMPK was reduced in HFD group (P<0.05). As compared with HFD group, the body weight gain, serum TG, TC, LDL-C, HDL-C and ALT levels were significantly reduced in RD group (P<0.01), and FBG level was also reduced (P<0.05). Moreover, RD treatment alleviated liver fat deposition and TG accumulation (P<0.01). The mRNA levels of SREBP1, ACC, and SCD1 were all reduced in RD group compared with HFD group. The protein level of pAMPK was increased, and the expression of Fasn was reduced with RD treatment (P<0.01). Conclusion Resistant dextrin improves liver fat deposition and activates the AMPK signaling pathway in HFD-fed mice.

Objective To investigate the differences in risk factors for cerebral hemorrhage between urban and rural areas in northern China to provide accurate prevention for cerebral hemorrhage in both urban and rural areas. Methods Data was collected from patients over 40 years old in different provinces in northern China, which was further divided into urban and rural groups. Condition matching method was used to analyze the risk factors and to compare these risk factors between urban and rural cerebral hemorrhage and. Results Data from 191,625 people were collected. Among 559 patients with cerebral hemorrhage, there were 251 and 308 patients in urban and rural areas, respectively Hypertension and lack of exercise had a stronger effect on cerebral hemorrhage in rural area [OR 95%CI (9.07,6.25～13.16)vs. (7.67,5.20～11.32)]、 [OR 95% CI (2.18,1.59～2.98)vs. (1.89,1.36～2.62)]. Family history of stroke, diabetes, and excessive overweight had bigger impacts on urban cerebral hemorrhage [OR 95%CI(5.40,3.48～8.36)vs.(5.09,3.37～7.68)]、[OR 95%CI(2.41,1.55～3.75)vs.(1.98,1.21～3.23)]、[OR 95%CI(2.38,1.69～3.35)vs.(1.71,1.26～2.32)]. Conclusions A more precise preventive measures can be developed based on the impact of different risk factors on urban and rural areas