AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.

AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.

[Objective] To investigate the infection status and characteristics of HEV among voluntary blood donors in Ningbo, and to provide a basis for improving the blood screening strategy. [Methods] A total of 12 227 blood samples from voluntary blood donors in Ningbo from June 2022 to May 2023 were tested for HEV serology, enzymology, and nucleic acid testing. Furthermore, HEV gene sequencing was performed for genotyping analysis, and donors with reactive nucleic acid testing results were followed up to confirm their infection status. [Results] The reactivity rate of HEV Ag, anti-HEV IgM and anti-HEV IgG was 0.098%, 0.899% and 29.198%, respectively. There was no difference in the reactivity of anti-HEV IgM and anti-HEV IgG between genders, donation frequencies and donation types (P>0.05). The reactivity rate increased significantly with age (P<0.05). The rate of ALT disqualification (ALT>50U/L) was significantly higher than that in non-reactive samples (P<0.05). The HEV Ag reactivity rate (0.098%) was not correlated with gender, donation frequency, donation type or age. One HEV RNA positive case was found, with a positive rate of 0.008%(1/12 227). It was confirmed to be hepatitis E virus genotype 3 by sequencing analysis. Apart from HEV Ag reactivity, all other blood safety screening items were non-reactive, suggesting this case might be in the acute infection phase. The follow-up results showed that all indicators of the donor's previous blood donation were non-reactive. [Conclusion] Pre-donation ALT detection can reduce the risk of transfusion-transmitted HEV (TT-HEV) to a certain extent, and the effective way to prevent TT-HEV is to detect HEV RNA and serology of donor blood.

Aim To predict the mechanism of action of ginsenoside Rg1(G-Rg1)paired with hirudin in the treatment of myocardial fibrosis in acute myocardial in-farction(AMI)based on the network pharmacology ap-proach,and to validate it by in vivo and in vitro experi-ments.Methods The corresponding targets of G-Rg1 and Hirudin were collected using SwissTargetPredic-tion,TargetNet,ETCM and ChEMBL databases,and the targets related to AMI and myocardial fibrosis were collected using GeneCards,OMIM and DisGeNET da-tabases.The drug-disease intersection targets were subjected to protein-protein interaction network(PPI)network analysis,gene ontology(GO)functional en-richment analysis and kyoto encyclopedia of genomes(KEGG)pathway enrichment analysis.Key targets and pathways were validated using an AMI mouse mod-el induced by ligation of the anterior descending branch of the left coronary artery in mice versus a hypoxia-in-duced injury model of human cardiac microvascular en-dothelial cells(HCMECs).Results G-Rg1 paired with hirudin had 229 drug targets,816 AMI and myo-cardial fibrosis disease targets,and 65 intersecting tar-gets.PPI analysis showed that tumor necrosis factor(TNF),interleukin-1[3(IL-1 β),transforming growth factor beta-1(TGF-β1),nuclear factor kappa-B(NF-κB),and interleukin-6(IL-6)might be the core tar-gets of G-Rg1 paired with Hirudin in the treatment of post-MI myocardial fibrosis;KEGG was enriched for a total of 141 pathways involving endocrine and metabo-lism,inflammation,and immunity,mainly TNF signa-ling pathway,PI3K/Akt signaling pathway and TGF-βsignaling pathway.In vivo experiments confirmed that G-Rg1 paired with hirudin attenuated myocardial fibro-sis after AMI in mice,and down-regulated the expres-sion of TNF-α,IL-1β,NF-κB,TGF-β1,and Smad2/3 proteins in myocardial tissues.In vitro experiments confirmed that G-Rg1 paired with Hirudin inhibited cellular NF-κB/TGF-β1 pathway,reduced hypoxia-in-duced cellular TNF-α and IL-1β expression,and su-perimposed NF-κB inhibitor significantly reduced IL-1 β expression and attenuated cellular inflammatory re-sponse.Conclusions G-Rg1 with Hirudin treats post-MI myocardial fibrosis by regulating TNF-α,IL-1 β and other targets and NF-KB/TGF-β1 pathway,reflecting its multi-pathway and multi-target action characteris-tics,and providing a pharmacological basis for the treatment of post-MI myocardial fibrosis with G-Rg1 with Hirudin.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective:To analyze the awareness of HCV infection status and willingness for HCV-RNA testing among hepatitis C cases in four provinces in China and to provide a reference for adjusting HCV prevention and control strategies.Methods:From September 2021 to September 2022, a cross-sectional survey was conducted using stratified random cluster sampling in four provinces (Jiangsu, Henan, Hubei, and Yunnan) in China, with an estimated sample size of 6 468 participants. The questionnaire included sociodemographic information, HCV infection awareness, willingness for HCV-RNA testing, and history of high-risk behaviors from the survey participants. Logistic regression models were used to analyze the factors associated with HCV infection awareness and willingness for HCV-RNA testing among hepatitis C cases. Statistical analysis was performed using R 4.1.3 software.Results:A total of 10 563 hepatitis C cases were surveyed. The awareness rate of HCV infection was 86.74% (9 162/10 563), and the willingness rate for HCV-RNA testing was 85.21% (9 001/10 563). Multivariate logistic regression models analysis showed that the awareness rate of HCV infection was lower among individuals aged ≥60 years, urban residents (with New Rural Cooperative Medical Insurance ), those without a history of blood transfusion, those without a history of paid blood donation, those without a history of injection drug use, and those without a family member with hepatitis C case.The awareness rate was higher among individuals with high or technical secondary school education, college education or above, and those married with a spouse (all P<0.05). In terms of willingness for HCV-RNA testing, it was lower among females, individuals aged ≥60 years, and those without a history of blood transfusion, paid blood donation, or injection drug use. The willingness was higher among farmers or migrant workers, employees of enterprises or institutions, and those in other occupations (all P<0.05). Conclusions:There was room for improvement in the awareness proportion of HCV infection and willingness for HCV-RNA testing among hepatitis C cases in the four provinces of China. More convenient policies and measures should be provided to increase the awareness rate of HCV infection and the willingness to undergo HCV-RNA testing in this population.

Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

Objective:To investigate the expression and methylation status of the SALL4 gene in placental tissues of fetal growth restriction (FGR) and its effects on trophoblast cell proliferation, migration, and invasion. Methods:Placental tissues were collected from 20 full-term FGR patients and 20 healthy term controls who underwent regular prenatal examination and cesarean section at the Third Affiliated Hospital, Zhengzhou University between July 2023 and February 2024. SALL4 mRNA and protein expression were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Methylation specific polymerase china reaction (MSP) assessed promoter methylation levels. HTR8/SVneo cells were transfected with SALL4-targeting small interfering RNA (si-SALL4) or negative control small interfering RNA (si-NC). HTR8/SVneo cells were treated with the demethylating agent 5-aza-2′-deoxycytidine (5-Aza-dC) to inhibit gene methylation (5-Aza-dC group) or with 10% RPMI-1640 medium as a vehicle control. Transfection efficiency (for siRNA) and the efficacy of 5-Aza-dC-induced demethylation were assessed by qRT-PCR and Western blot. The functional effects of SALL4 knockdown and methylation inhibition on trophoblast cells were evaluated using proliferation assays, scratch wound healing assays, and Transwell invasion assays. Statistical analyses included independent t-tests and Chi-square test. Results:(1) Human tissues: FGR placentas showed lower SALL4 mRNA (0.802±0.194 vs. 1.015±0.186, t=3.55) and protein expression (0.445±0.114 vs. 0.701±0.113, t=3.19), alongside higher methylation rates of SALL4 [80% (16/20) vs. 15% (3/20), χ2=14.44] compared to controls (all P<0.05). (2) In vitro: si-SALL4 transfection reduced HTR8/SVneo proliferation (OD450 at 48 h: 0.653±0.021 vs. 0.827±0.040, t=6.60), migration [healing rate at 48 h: (24.317±2.637)% vs. (49.327±1.961)%, t=13.18], and invasion [counted invaded cells: (133.000±6.557) vs. (272.667±18.009) cells, t=12.62] versus si-NC (all P<0.05). Conversely, 5-Aza-dC treatment increased HTR8/SVneo proliferation (0.917±0.042 vs. 0.783±0.031, t=－4.47), migration [(71.097±3.354)% vs. (51.632±2.877)%, t=－7.63], and invasion [(384.000±12.166) vs. (202.833±7.095) cells, t=－13.69] versus vehicle control (all P<0.05). Conclusions:Hypermethylation of the SALL4 promoter in FGR placentas suppresses its expression, impairing trophoblast cell function. Demethylation restores SALL4 expression and enhances cellular proliferation, migration, and invasion, involving in the occurrence and development of FGR disease.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective To analyze the clinical characteristics of cancer related anemia(CRA)in older cancer patients undergoing multi-line anti-tumor treatment.Methods A cross-sectional study was conducted,including patients with CRA who were≥65 years old and had received or were currently undergoing multi-line treatment at 9 hospitals in Beijing from June 1,2018 to September 30,2023.Data on gender,age,past history,family history,tumor type,metastasis site,clinical symptoms,blood routine,specialized examination for anemia,anti-tumor and anemia correction treatment were collected.The basic characteristics of the included patients,clinical symptoms,the status of blood cell reduction,treatment conditions,and the distribution of traditional Chinese medicine(TCM)syndrome characteristics were analyzed.Results A total of 602 patients were included.The tumor types included lung cancer,colorectal cancer,gastric cancer,esophageal cancer,breast cancer,gynecological tumors,lymphoma.The overall median hemoglobin(HGB)level was 99.00(88.00,107.00)g/L.The HGB levels of patients with different tumor types showed significant differences(P<0.001).The HGB levels of patients with gynecological tumors were significantly lower than those of patients with colorectal cancer,lung cancer and esophageal cancer(P<0.05).The most common clinical symptoms were fatigue,loss of appetite,irregular bowel movements and pain.In terms of anti-tumor treatment,405 patients were receiving multi-line anti-tumor treatment(including combined chemotherapy,combined radiotherapy,combined targeted therapy,and combined immunotherapy),197 patients were receiving symptomatic supportive treatment after multi-line anti-tumor treatment.In terms of anemia correction treatment,183 patients received erythropoietin,folic acid,iron,vitamin B12,or blood transfusion,while 293 patients received TCM for correcting anemia(including Chinese patent medicines,Chinese herbal decoctions,combinations of Chinese patent medicines and Chinese herbal decoctions).Specialized tests for anemia,such as serum iron,total iron binding capacity,transferrin saturation,transferrin,erythropoietin et al,have a detection rate of only 3.65%～27.91%.In terms of the characteristics of TCM syndromes,the main TCM syndrome types of the patients were as follows:syndrome of spleen-stomach weakness,syndrome of qi and blood deficiency,syndrome of heart-spleen deficiency,syndrome of spleen-kidney yang deficiency,syndrome of liver and kidney yin deficiency.Some patients also have the accompanying symptoms of internal binding of static blood and poison,phlegm dampness retention.Further comparison revealed that the HGB level of older patients with CRA who had syndrome of spleen-stomach weakness was significantly lower than patients with other symptom types(P<0.001).The HGB level of patients with syndrome of qi and blood deficiency was significantly lower than patients with syndrome of spleen-kidney yang deficiency(P<0.01)and syndrome of liver and kidney yin deficiency(P<0.001).Patients with symptoms of internal binding of static blood and poison,or symptoms of phlegm dampness retention had significantly lower HGB levels compared to those without accompanying symptoms(P<0.01).Conclusion The rate of specialized blood test for anemia in older patients with CRA was relatively low.The most common TCM syndrome types were syndrome of spleen-stomach weakness and syndrome of qi and blood deficiency.The overall treatment rate was also low.The screening,specialized diagnosis and monitoring of older patients with CRA need to be given more attention,and treatment methods such as TCM,Western medicine,and integrated TCM-Western medicine should be selected based on the patient's condition.