Objective:This study investigated the dynamic expression of lipocalin-2(LCN2)and its receptor,brain-type organic cation transporter protein(BOCT),in spinal cords of hSOD1G93A transgenic mice during disease pro-gression,providing potential targets for early anti-inflammatory therapy for ALS.Methods:Utilizing hSOD1G93A trans-genic mice and their wild-type littermates(WT)as animal models,this investigation examined the expression of LCN2 and BOCT at four distinct disease stages:pre-symptomatic stage(60 d),early-symptomatic stage(95 d),symptomatic stage(108 d),and late-symptomatic stage(122 d).Spinal cords were harvested,then RT-qPCR,Western blot,and immunofluorescence double-labeling techniques were employed to assess alteration expressions of LCN2 and BOCT.Ad-ditionally,BV2 cells transfected with the pcDNA3.1-G93A-SOD1 overexpression plasmid served as an in vitro hSOD1G93A BV2 microglial model.After stimulated with LPS for 24 hours,LCN2 mRNA and protein expression in hSOD1G93A BV2 microglial cells and its culture medium were measured by RT-qPCR and ELISA respectively,while BOCT expression was measured by Western blot.Results:Compared with WT mice littermates,increased expression of LCN2 mRNA was detected in the spinal cords of hSOD1G93A transgenic mice at 108 and 122 d.No significant differences were observed in LCN2 or BOCT protein expression in the spinal cords of hSOD1G93A transgenic mice from 60 to 122 d.Double-immunofluorescence labeling revealed co-localization of LCN2 and BOCT with the microglial marker Iba-1 in the ventral horn of lumbar spinal cord of hSOD1G93A transgenic mice from 95 to 122 d.In hSOD1G93A BV2 microglial model,LPS stimulation led to a significantly increased LCN2 mRNA expression and protein secretion.Conversely,there was no significant change in BOCT protein expression after LPS stimulation.Conclusion:Our findings suggest that during ALS progression,there is an enhanced expression and release of LCN2 from activated microglia,potentially exacerbating neuroinflammation and neuronal degeneration.

Objective:This study investigated the dynamic expression of lipocalin-2(LCN2)and its receptor,brain-type organic cation transporter protein(BOCT),in spinal cords of hSOD1G93A transgenic mice during disease pro-gression,providing potential targets for early anti-inflammatory therapy for ALS.Methods:Utilizing hSOD1G93A trans-genic mice and their wild-type littermates(WT)as animal models,this investigation examined the expression of LCN2 and BOCT at four distinct disease stages:pre-symptomatic stage(60 d),early-symptomatic stage(95 d),symptomatic stage(108 d),and late-symptomatic stage(122 d).Spinal cords were harvested,then RT-qPCR,Western blot,and immunofluorescence double-labeling techniques were employed to assess alteration expressions of LCN2 and BOCT.Ad-ditionally,BV2 cells transfected with the pcDNA3.1-G93A-SOD1 overexpression plasmid served as an in vitro hSOD1G93A BV2 microglial model.After stimulated with LPS for 24 hours,LCN2 mRNA and protein expression in hSOD1G93A BV2 microglial cells and its culture medium were measured by RT-qPCR and ELISA respectively,while BOCT expression was measured by Western blot.Results:Compared with WT mice littermates,increased expression of LCN2 mRNA was detected in the spinal cords of hSOD1G93A transgenic mice at 108 and 122 d.No significant differences were observed in LCN2 or BOCT protein expression in the spinal cords of hSOD1G93A transgenic mice from 60 to 122 d.Double-immunofluorescence labeling revealed co-localization of LCN2 and BOCT with the microglial marker Iba-1 in the ventral horn of lumbar spinal cord of hSOD1G93A transgenic mice from 95 to 122 d.In hSOD1G93A BV2 microglial model,LPS stimulation led to a significantly increased LCN2 mRNA expression and protein secretion.Conversely,there was no significant change in BOCT protein expression after LPS stimulation.Conclusion:Our findings suggest that during ALS progression,there is an enhanced expression and release of LCN2 from activated microglia,potentially exacerbating neuroinflammation and neuronal degeneration.

AIM To investigate the effects of Liangxue Heying Formula-medicated serum(LXHY-MS)on human umbilical vein endothelial cells(HUVECs)induced by lipopolysaccharide(LPS).METHODS CCK-8,DCFH-DA fluorescence probe and Western blot method were used to screen the LPS concentration in modeling and the serum LXHY concentration for treatment.The HUVECs divided into the normal group,the model group and the LXHY-MS group had their SOD activity detected by automatic biochemical analyzer;their MDA level detected by colorimetry;their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 detected by Western blot;and their mROS expression and recruitment effect on THP-1 photographed with high connotation.With the use of JAK2/STAT3 pathway inhibitor(AG490),the HUVECs divided into the normal group,the AG490 group,the LPS group,the LPS+AG490 group,the LPS+LXHY-MS group,and LPS+LXHY-MS+AG490 group were subjected to the corresponding treatment,followed by the detection of their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 by Western blot.RESULTS Compared with the normal group,the model group displayed decreased SOD activity(P＜0.01),increased MDA level(P＜0.05),increased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P＜0.05,P＜0.01),and increased mROS expression and THP-1 cells recruitment.Compared with the model group,the LXHY-MS group shared increased SOD activity(P＜0.05),decreased MDA level(P＜0.01),decreased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P＜0.05,P＜0.01),reduced mROS expression and THP-1 cells recruitment.Given the use of AG490,the model group displayed increased protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 in contrast to the normal group(P＜0.05,P＜0.01);each intervened group showed decreased expressions of related proteins in contrast to the model group(P＜0.05,P＜0.01).CONCLUSION LXHY-MS may protect the injury due to the activation of HUVECs by inhibiting the JAK2/STAT3 signaling pathway.

Objective To analyze the serum metabolomic changes of preterm infants with bronchopulmonary dysplasia(BPD)at postmenstrual age(PMA)36 weeks,screen potential biomarkers and associated metabolic pathways,and assess their relationship with short-term respiratory outcomes.Methods A retrospective case-control study was conducted.Infants with gestational age 28-32 weeks admitted to the Children's Hospital Affiliated to Zhengzhou University from January to December 2024 were included.Twenty infants with BPD and 20 gestational age-,birth weight-,and sex-matched non-BPD preterm infants were included.Serum collected at PMA 36 weeks was subjected to untargeted metabolomics analysis,and associations with short-term respiratory outcomes were analyzed.Results Thirteen potential biomarkers distinguishing BPD were identified(area under the curve>0.75,P<0.05).Eight biomarkers—including terephthalic acid,phosphatidylinositol,fumarate,and lysophosphatidic acid—were significantly upregulated(FC≥1.5),while five biomarkers,such as 7α-hydroxy-3-oxo-4-cholestenoate ester and phosphatidylcholine,were significantly downregulated(FC≤1/1.5).Pathway analysis indicated five pathways associated with BPD,including glycerophospholipid metabolism and phenylalanine metabolism.Dysregulation of glycerophospholipid and bile acid metabolism may affect adverse short-term respiratory outcomes in infants with BPD.Conclusions The 13 significantly different metabolites may serve as biomarkers for the diagnosis of BPD.Glycerophospholipid metabolism is associated with the occurrence of BPD and with adverse short-term respiratory outcomes.

Objective To analyze the serum metabolomic changes of preterm infants with bronchopulmonary dysplasia(BPD)at postmenstrual age(PMA)36 weeks,screen potential biomarkers and associated metabolic pathways,and assess their relationship with short-term respiratory outcomes.Methods A retrospective case-control study was conducted.Infants with gestational age 28-32 weeks admitted to the Children's Hospital Affiliated to Zhengzhou University from January to December 2024 were included.Twenty infants with BPD and 20 gestational age-,birth weight-,and sex-matched non-BPD preterm infants were included.Serum collected at PMA 36 weeks was subjected to untargeted metabolomics analysis,and associations with short-term respiratory outcomes were analyzed.Results Thirteen potential biomarkers distinguishing BPD were identified(area under the curve>0.75,P<0.05).Eight biomarkers—including terephthalic acid,phosphatidylinositol,fumarate,and lysophosphatidic acid—were significantly upregulated(FC≥1.5),while five biomarkers,such as 7α-hydroxy-3-oxo-4-cholestenoate ester and phosphatidylcholine,were significantly downregulated(FC≤1/1.5).Pathway analysis indicated five pathways associated with BPD,including glycerophospholipid metabolism and phenylalanine metabolism.Dysregulation of glycerophospholipid and bile acid metabolism may affect adverse short-term respiratory outcomes in infants with BPD.Conclusions The 13 significantly different metabolites may serve as biomarkers for the diagnosis of BPD.Glycerophospholipid metabolism is associated with the occurrence of BPD and with adverse short-term respiratory outcomes.

Objective To analyze the application effect of acetaminophen preemptive analgesia combined with intercostal nerve block in thoracoscopic lobectomy.Methods A total of 120 patients with lung cancer who underwent thoracoscopic lobectomy admitted to Lu'an Traditional Chinese Medicine Hospital from January 2021 to September 2023 were selected as the study objects,and they were divided into the control group and the observation group according to random number table method,with 60 cases in each group.Patients in the control group were given acetaminophen preemptive analgesia before anesthesia induction,while patients in the observation group were given intercostal nerve block on the basis of the control group.The visual analogue scale(VAS)score,Ramsay sedation score,serum β-endorphin level and prostaglandin E2 level 3,12,24 and 48 hours after operation of patients in the two groups were compared.The stress response indexes such as norepinephrine(NE),epinephrine(E)and serum cortisol(Cor),as well as immune function indexes such as CD3+,CD4+and CD4+/CD8+before anesthesia induction and after extubation of patients in the two groups were compared.The incidence of adverse reactions after extubation of patients in the two groups were compared.Results The VAS scores of patients after surgery in the two groups gradually increased with time,and the Ramsay sedation scores gradually decreased with time.The VAS scores of patients in the observation group were lower than those in the control group at each postoperative time point,and the Ramsay sedation scores were higher than those in the control group,with statistically significant differences(P<0.05).The levels of serum β-endorphin and prostaglandin E2 of patients after surgery in the two groups gradually decreased with time.The levels of serum β-endorphin of patients at each postoperative time point in the observation group were higher than those in the control group,and the levels of prostaglandin E2 of patients at each postoperative time point in the observation group were lower than those in the control group,with statistically significant differences(P<0.05).The levels of NE,E,and Cor after extubation of patients in the two groups were significantly decreased(P<0.05),and those in the observation group were lower than those in the control group(P<0.05).The levels of CD3+,CD4+,and CD4+/CD8+after extubation of patients in the two groups were significantly decreased(P<0.05),and those in the observation group were higher than those in the control group(P<0.05).The total incidence of adverse reactions in the observation group was lower than that in the control group,with statistically significant difference(P<0.05).Conclusion The application of acetaminophen preemptive analgesia combined with intercostal nerve block in thoracoscopic lobectomy has good analgesic and sedative effects on patients,which is helpful to improve patients'immune function and reduce postoperative adverse reactions.

Objective:To explore the clinical and biochemical characteristics of patients with hyperuricemia according to different pathophysiological subtypes. This may facilitate rapid identification of each subtype in clinical settings and provide evidence for personalized urate-lowering treatment.Methods:Patients diagnosed with hyperuricemia at the Department of Endocrinology and Metabolism, Tenth People′s Hospital of Tongji University between October 2015 and January 2024 were included. Based on 24-h urinary uric acid excretion(UUE) and the fractional excretion of uric acid(FEUA), patients were classified into four subtypes: renal uric acid underexcretion type(RUE), renal uric acid overload type(ROL), combined type and renal normal type. Clinical and biochemical variables-including sex, age, BMI, smoking history, comorbidities, blood glucose, and serum uric acid-were analyzed. Binary logistic regression was used to identify factors associated with each subtype.Results:Among 2 073 patients with hyperuricemia, 55.8% were RUE type, 6.9% were ROL type, 31.3% were combined type and 6.0% were renal normal type. RUE type had lower blood glucose levels and fewer cases of diabetes [ OR=0.685(95% CI 0.478-0.980), P<0.05]. ROL type showed a higher incidence of tophi, positively correlated with smoking history [ OR=1.672(95% CI 1.009-2.771), P<0.05], and negatively correlated with serum uric acid levels [ OR=0.994(95% CI 0.990-0.998), P=0.001]. Combined type had the youngest onset age, shortest disease duration, and the fewest comorbidities, and was associated with higher BMI [ OR=1.035(95% CI 1.001-1.070), P<0.05]. Renal normal type had the oldest age of onset, the highest proportion of female patients and comorbidities, and was associated with lower serum uric acid levels[ OR=0.994(95% CI 0.989-0.998), P=0.007], higher BMI[ OR=1.064(95% CI 1.003-1.129), P<0.05], and increased tophi incidence[ OR=2.261(95% CI 1.206-4.237), P=0.011]. Conclusion:Each pathophysiological subtype of hyperuricemia exhibits distinct clinical and biochemical characteristics, which may serve as useful references for subtype identification and personalized management in clinical practice.

Objective: To screen the frequency of CD36 antigen expression in platelet donor database in Shaanxi province and analyze the molecular genetic characteristics of samples with CD36 antigen deficiency and low expression. Methods: A total of 525 platelet donors samples were randomly collected during May 2023. CD36-FITC monoclonal antibody was used for immunofluorescence labeling, and flow cytometry was applied to detect the expression of CD36 antigen on platelets. For samples with CD36 antigen deficiency on platelets, the expression of CD36 on monocytes was further detected. Samples with CD36 antigen deficiency and low expression were sequenced and analyzed. Results: Among the 525 blood samples, 99.24% (521/525) showed positive expression of CD36 antigen. There were differences in the expression intensity of CD36 antigen, with low expression accounting for 3.43% (18/525) and CD36 antigen deficiency accounting for 0.76% (4/525), all of which were type Ⅱ deficiency. The exon mutation frequency of CD36 type Ⅱ deficiency and low expression samples was 31.82% (7/22), and the exon mutation types were 121-1_126delGCAAGTT, 329-330delAC, 1142T>G, 1204-1246dupl 43bp, 1221G>A, and 1228-1239delATTGTGCCTATT. All four cases of CD36 type Ⅱ deficiency had a 121-6 T>C mutation in intron 3. All CD36 low expression samples had a mutation of 282-10A>G, and 121-6T>C mutation rate was 61.1%(11/18). Conclusion: There were differences in the expression of CD36 antigen in the platelet donor database in Shaanxi province, which may be caused by multiple molecular genetic variations. The frequency of CD36 antigen deficiency in Shaanxi was lower than that of Han, Zhuang and Yao populations in southern China. This study provides references for solving the CD36 antibody mediated transfusion reaction and auxiliary treatment of diseases caused by CD36 antigen deficiency in the future. It also provides a basis for investigating the molecular mechanisms of CD36 deficiency and low expression.

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.
Male ; Humans ; Autophagy/physiology* ; Apoptosis/physiology* ; Erectile Dysfunction/physiopathology* ; Fibrosis ; Penis/pathology* ; Animals ; Endothelial Cells/pathology* ; Myocytes, Smooth Muscle/pathology*