Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To measure pancreatic fat deposition by magnetic resonance chemical shift imaging (CSI), and analyze the correlation between pancreatic fat deposition and pancreatic fistula after pancreaticoduodenectomy (PD).Methods:A retrospective analysis was conducted on the data of 55 patients who underwent PD in the Affiliated Hospital of Xuzhou Medical University from September 2021 to April 2024. Among them, 34 were male (61.8%) and 21 were female (38.2%), with the age of (63.5±12.0) years. The 55 patients included 17 cases (30.9%) of pancreatic ductal adenocarcinoma, 1 case (1.8%) of pancreatic serous cystadenoma, 2 cases (3.6%) of pancreatic mucinous cystadenoma, 1 case (1.8%) of pancreatic solid pseudopapillary tumor, 11 cases (20.0%) of ampullary carcinoma, 10 cases (18.2%) of common bile duct carcinoma, and 13 cases of other pathological types (such as high-grade intraepithelial neoplasia of the ampullary gland, duodenal adenocarcinoma, etc.) (23.6%). Before the operation, pancreatic fat deposition was measured by CSI and the fat fraction was calculated. With a fat fraction of 6.2% as the cut-off value, 55 patients were divided into the normal pancreas group (fat fraction ≤ 6.2%, n=29) and the fat pancreas group (fat fraction > 6.2%, n=26). The total hospitalization cost, postoperative hospital stay, biochemical leakage, grade B pancreatic fistula of the two groups were compared, and the correlation between pancreatic fat fraction and pancreatic fistula was analyzed. Result:The total hospitalization cost in the normal pancreas group was (91 527.3±19 118.4) yuan, and the postoperative hospital stay was 9.0 (8.0, 13.0) days, both of which were lower than those in the fatty pancreas group (107 772.4 ± 27 055.6) yuan and 11.0 (8.0, 22.0) days, and the differences were statistically significant ( t=-2.59, P=0.012; Z=-2.08, P=0.038). In the normal pancreas group, 8 cases (27.6%) of biochemical leakage and 1 case (3.4%) of grade B pancreatic fistula occurred after the operation. In the fat pancreas group, 10 cases (38.5%) of biochemical leakage and 8 cases (30.8%) of grade B pancreatic fistula occurred after the operation. There was no statistically significant difference in the incidence of biochemical leakage between the two groups ( χ2=0.74, P=0.391). The incidence of grade B pancreatic fistula after surgery in the adipose pancreas group was significantly higher than that in the normal pancreas group, and the difference was statistically significant ( χ2=5.61, P=0.018). The relationship between pancreatic body fat fraction and the occurrence of pancreatic fistula is correlated (the correlation coefficient was 0.334, 95% CI: 0.127-0.515, P=0.013) The relationship between the overall fat fraction of the pancreas and the occurrence of pancreatic fistula is correlated (the correlation coefficient was 0.472, 95% CI: 0.235-0.689, P<0.001). Conclusions:The incidence of grade B pancreatic fistula after PD in patients with a low fat fraction of the pancreas measured by CSI was lower than that in patients with a high fat fraction. Fat deposition in the pancreatic body and the pancreas as a whole is associated with the incidence of pancreatic fistula.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective To develop and validate a nomogram incorporating postoperative blood pressure and other multifactorial predictors for the risk of delayed cerebral ischemia(DCI)following surgical clipping in patients with aneurysmal subarachnoid hemorrhage(aSAH).Methods This retrospective cohort study consecutively enrolled 272 aSAH patients who underwent aneurysm clipping at the Department of Neurosurgery,Second Affiliated Hospital of Chongqing Medical University from January 2018 to January 2022.Demographic,clinical,and imaging data were collected.Predictors were screened using LASSO regression,and a multifactorial logistic regression-based nomogram was constructed.The dataset was randomly divided into training(n=190)and validation(n=82)sets at a 7∶3 ratio.Model discrimination,calibration,and clinical utility were evaluated using the area under the receiver operating characteristic curve(AUC),calibration curves,and decision curve analysis(DCA),respectively.Results Among 272 enrolled patients,98(36%)developed DCI.Multivariate analysis identified age(OR=0.97;95%CI:0.94～0.99;P=0.036),World Federation of Neurological Surgeons(WFNS)grade(OR=1.36;95%CI:1.02～1.82;P=0.038),Fisher grade(OR=1.44;95%CI:1.01～2.05;P=0.048),and mean arterial pressure on postoperative day 2(OR=1.06;95%CI:1.03～1.09;P<0.001)as independent risk factors for DCI.The model achieved C-indices of 0.739(95%CI:0.668～0.810)in the training set and 0.760(95%CI:0.647～0.872)in the validation set.Calibration curves demonstrated high agreement between predicted and observed probabilities(mean absolute error=0.027),while DCA confirmed significant net clinical benefit at threshold probabilities of 15%～65%.Conclusion We successfully developed a predictive model incorporating age,WFNS grade,Fisher grade,and postoperative day 2 mean arterial pressure,with elevated postoperative blood pressure identified as an early critical indicator for DCI development.

OBJECTIVE: To detect and analyze the expression and clinical significance of long non-coding RNA tyrosine kinase non-catalytic region adaptor protein 1-antisense RNA1 (NCK1-AS1) in patients with acute myeloid leukemia (AML). METHODS: 89 AML patients and 23 healthy controls were included from the People's Hospital Affiliated to Jiangsu University. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of NCK1-AS1 and NCK1 in bone marrow samples. The relationship between the expression of NCK1-AS1 and the clinical characteristics of patients were analyzed, as well as the correlation between NCK1-AS1 and NCK1. RESULTS: The expression level of NCK1-AS1 in all AML, non-M3 AML and cytogenetically normal AML (CN-AML) patients was significantly higher than that in the control group (P < 0.01, P < 0.05, P < 0.01, respectively). In non-M3 AML, patients with high NCK1-AS1 expression had a significantly lower hemoglobin level than those with low NCK1-AS1 expression (P =0.036), furthermore, NCK1-AS1 ^high patients had shorter overall survival than NCK1-AS1^low patients (P =0.0378). Multivariate analysis showed that NCK1-AS1 expression was an independent adverse factor in patients with non-M3 AML ( HR =2.392, 95% CI :1.089-5.255, P =0.030). In addition, NCK1 expression was also significantly upregulated in all AML, non-M3 AML and CN-AML patients compared with controls (P < 0.01, P < 0.01, P < 0.001, respectively). There was a certain correlation between NCK1-AS1 and NCK1 expression (r =0.37, P =0.0058). CONCLUSION High expression of NCK1-AS1 in AML indicates poor prognosis of AML patients.
Humans ; Leukemia, Myeloid, Acute/genetics* ; RNA, Long Noncoding/genetics* ; Oncogene Proteins/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Prognosis ; Male ; Female ; Middle Aged ; Adult ; Case-Control Studies ; Clinical Relevance

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the acupoint selection law of acupuncture and moxibustion in the treatment of broca aphasia after stroke.Methods:RCT articles about acupuncture and moxibustion treatment for broca aphasia after stroke were retrieved from CNKI, VIP, Wanfang Data, China Medical Journal Full-text Database, SinoMed, PubMed, Web of Science and Embase database from the establishment of the databases to May 31, 2024. Excel 2021, SPSS Statistics 27.0, SPSS Modeler 18.0 and Cytoscape 3.9.1 software were used to analyze the frequency of acupoint, clustering, association rules and core co-occurrence network.Results:A total of 87 articles were included, involving 100 acupuncture and moxibustion prescriptions and 101 acupoints/acupoint area, involving 6 types, including Lianquan (CV 23) (35 times), Jinjin (EX-HN12) (35 times) and Yuye (EX-HN13) (34 times). The selected acupoints were mainly distributed in the head, face, neck and lower limbs, and the meridians were mainly Governor Vessel and Conception Vessel; the specific acupoints were mainly original acupoints, followed by collaterals acupoints, and scalp acupuncture was used most frequently in special acupuncture (88 times). According to the clustering analysis of high-frequency acupoints/acupoint area, there were five effective groups, such as "Jinjin (EX-HN12)-Yuye (EX-HN13)-Lianquan (CV 23)-Baihui (GV 20)-Yamen (GV 15)". The core co-occurrence network analysis showed that the acupoints used most frequently were Lianquan (CV 23) and Jinjin (EX-HN12), and the highest correlation between the two acupoints was Jinjin (EX-HN12)-Yuye (EX-HN13).Conclusions:Acupuncture and moxibustion for the treatment of broca aphasia after stroke is often based on "awakening the brain as the outline, benefiting the marrow as the foundation, and resuscitation". Under the guidance of the theory of Zang-fu meridians and collaterals, through dredging the meridians and collaterals, tonifying the brain and opening and closing the sound, the recovery of language function can be achieved.