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.

Total-body PET/CT, with its long axial field of view and high sensitivity detector, has shown potential for reducing the dose of radiopharmaceuticals. However, pediatric patients are significantly more sensitive to radiation and have a higher long-term cancer risk than adults, posing fundamental challenges for dose management in PET/CT examinations for these patients. In this article, the technical characteristics of total-body PET/CT and its radiation exposure status in children were systematically analyzed. The radiation exposure could be controlled by the following optimization strategies: adjusting the CT exposure parameters, optimizing the scanning mode, adding reconstruction algorithm, and reducing the injected dose of radioactive tracer. By addressing both external and internal radiation during the PET/CT scanning process, the overall radiation dose received by pediatric patients can be reduced within a certain range. In addition, this article also discusses the technical differences between “total-body” and “whole-body” concepts, and emphasizes that the future optimization of radiation dose in pediatric PET/CT should be realized by integration of personalized scanning protocols. Through reasonable management of scanning protocols and processes, low-dose and high-quality PET/CT imaging can be achieved in clinical environments, thus maximizing protection of pediatric patient health while minimizing the risks associated with ionizing radiation exposure.

Objective: To retrospectively analyze the clinical data of 474 newborns with hyperbilirubinemia, and to investigate the clinical characteristics of hyperbilirubinemia caused by ABO hemolytic disease of the fetus and newborn (ABO-HDFN) and factors influencing the phototherapy duration. Methods: A total of 474 neonates with hyperbilirubinemia treated in the First Hospital of Lanzhou University from January 2019 to January 2023 were enrolled. Blood type identification and the standard serological tests (direct antiglobulin test, serum free antibody test, and antibody elution test) were performed for all neonates. Baseline clinical data were collected and analyzed. According to the results of the hemolysis tests, neonates were divided into hemolytic jaundice group and non-hemolytic jaundice group. Clinical indicators, including hemoglobin levels, length of hospital stay, and phototherapy duration, were compared between the two groups. A multiple linear regression model was used to explore clinical factors influencing the duration of phototherapy. Results: Among the 474 neonates with hyperbilirubinemia, 354 were diagnosed with ABO-HDFN (hemolytic group), while 120 were without ABO-HDFN (non-hemolytic group). The incidence of ABO-HDFN in neonates with blood type A (55.93%, 198/354) was significantly higher than those with blood type B (44.07%, 156/354) (P<0.05). Furthermore, neonates born to multiparous women had a significantly higher ABO-HDFN incidence (81.56%, 146/179) than first-born neonates (70.51%, 208/295) (P<0.05). Neonates in the hemolytic group had significantly lower hemoglobin levels (170.67±21.86 g/L vs 178.99±22.05 g/L, P<0.001), lower red blood cell counts (4.66±0.63×10 /L vs 4.89±0.59×10 /L, P<0.05), and lower hematocrit (50.05±6.56% vs 52.61±6.75%, P<0.05) compared to the non-hemolytic group. Additionally, the hemolytic group had significantly longer hospital stays (6 [5, 9] days vs 6 [4, 8] days), longer phototherapy duration (62 [38, 84.25] h vs 53 [34.25, 64.77] h), and higher frequency of jaundice episodes (9 [7, 13] times vs 8 [6, 12] times] compared to the non-hemolytic group (all P<0.05). Regression analysis indicated that a positive indirect Coombs test and multiparity were independent risk factors associated with prolonged phototherapy duration (P<0.05). Conclusion: ABO incompatibility is the leading cause of hemolytic disease in neonates, particularly in cases where the mother has blood type O and the neonate has blood type A. In such cases, close monitoring of bilirubin levels is strongly recommended. Multiparous pregnancies increase the risk of alloimmune hemolysis. Therefore, neonates born to multiparous women may require more frequent bilirubin monitoring and appropriate prenatal interventions when necessary. Additionally, changes in indicators such as hemoglobin level and red blood cell count should be closely monitored as early warning indicators for hemolytic anemia and bilirubin elevation.

Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.

Tuberculosis （TB） and human immunodeficiency virus infection / acquired immune deficiency syndrome （HIV/AIDS） are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years， with the promotion and application of new TB and HIV detection technologies worldwide， TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening， summarizes important progress of research and applications， and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.

This paper applied gas chromatography-mass spectrometry (GC-MS), network pharmacology and nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) metabolomics techniques to study the material basis and mechanism of action of Ning Shen Essential Oil in anti-insomnia. The main volatile components of Ning Shen Essential Oil were analyzed by gas chromatography-mass spectrometry (GC-MS), and the insomnia-related targets were predicted using the Traditional Chinese Medicine Systematic Pharmacology Database and Analytical Platform (TCMSP) and the databases of GeneCards, OMIM and Drugbank. The insomnia model of rats was replicated by intraperitoneal injection of 4-chloro-DL-phenylalanine (PCPA). Animal experiments were approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Ethics No.: SDUTCM20221025010). The modulating effect of Compound Ning Shen Essential Oil on anxiety behavior of rats was evaluated by behavioral related indexes. The serum levels of corticotropin-releasing hormone (CRH), adrenotropic corticotropic hormone (ACTH) and melatonin (MT) were measured by enzyme-linked immunoassay (ELISA). Rat serum and hippocampus were taken for nuclear magnetic resonance (¹H NMR) metabolomics to detect the changes of endogenous metabolites in rat serum hippocampus, to designate the differential metabolites and to construct metabolic pathways. The results showed that the exercise distance in the open field experiment and the number of times and time to enter the open arm in the elevated cross maze experiment of the rats in the model group were significantly reduced (P < 0.05, P < 0.01). The behavioral indexes of rats improved to different degrees after the administration of Ning Shen Essential Oil. The serum CRH and ACTH levels of rats in the model group increased significantly (P < 0.05, P < 0.01), and the MT level decreased significantly (P < 0.01); After the intervention, serum CRH and ACTH levels were reduced to different degrees, and MT levels could be regressed. ¹H NMR metabolomics screened 10 potential biomarkers related to insomnia, which involved in 6 potential metabolic pathways. A total of 35 components of Ning Shen Essential Oil were detected by GC-MS, the main component targets of Ning Shen Essential Oil and insomnia disease targets were intersected, a total of 172 intersecting genes were screened, and 26 core targets were identified. The study demonstrated that Ning Shen Essential Oil had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of the hypothalamic-pituitary-adrenal axis (HPA) related hormones and metabolism of amino acids, lipids and choline.

AIM:To study whether glycyrrhizic acid(GL)can resist the ototoxicity of cisplatin(CDDP)in mice and its molecular mechanism.METHODS:Male C57BL/6J mice were divided into 5 groups:control group,DMSO(5%)group,CDDP(4 mg/kg)group,CDDP+low-dose(50 mg/kg)GL group,and CDDP+high-dose(100 mg/kg)GL group(n=14).Auditory brainstem response(ABR)was used to detect hearing changes of mice.HE staining was used to observe the morphological change of cochlear stria vascular in mice.Evans blue(EB)staining was used to observe the per-meability change of the blood-labyrinth barrier(BLB).Immunohistochemical technique was used to detect the expression and distribution of adhesion protein VE-cadherin and tight junction protein ZO-1 on the cochlear stria.ELISA assay and immunofluorescence technology were employed to detect the expression of tumor necrosis factor-α(TNF-α)and interleu-kin-1β(1L-1β).RESULTS:In CDDP group,ABR waveforms of all frequencies were disturbed,the hearing threshold was significantly increased,and I wave latency was prolonged(P＜0.05).In CDDP+GL group,ABR waveforms of various frequencies were well differentiated,the hearing threshold was significantly decreased,and the latency of I-wave was shortened(P＜0.01).The disordered morphology and more vacuoles in the stria vascularis were observed by HE staining in CDDP group.The GL alleviated CDDP-induced damage in the stria vascularis.In EB staining,CDDP caused an increase in per-meability of BLB(P＜0.01),which was improved by GL treatment(P＜0.01).Immunohistochemical results showed that the expression of VE-cadherin and ZO-1 in CDDP group were decreased(P＜0.01),which was restored in CDDP+GL group(P＜0.01).The ELISA and immunofluorescence results showed that the expression of IL-1β and TNF-α was in-creased after CDDP treatment(P＜0.01),which was restored in CDDP+GL group(P＜0.01).CONCLUSION:The GL alleviates CDDP-induced hearing loss in mice by inhibiting CDDP-induced inflammation and reducing the permeability of BLB.

Objective:To investigate the influencing factors of urinary system symptoms in urban and rural residents aged 35 years old and above in Anhui province.Methods:A total of 19 339 residents aged 35 years old and above were selected from 19 counties(districts)of 9 cities in Anhui Province by multi-stage stratified cluster random sampling method.Binary logistic regression was used to analyze the influencing factors of urinary system symptoms.Results:There were statistically significant differences among different gender,age,long-term residence,body mass index and education level in the other 3 symptoms except urinary secretions(P＜0.05).Binary logistic regression analysis model showed that with the increase of age,the risk of frequent urination/urgent urination/painful urination,eyelid or lower limb edema increased,OR values were all＞1.Body mass index≥24 kg/m2 was the risk factor of frequent urination/urgent urination/painful urination,eyelid or lower limb edema(P＜0.05).People who lived in rural areas for a long time had a lower risk of blood urination(OR=0.79,P＜0.05).The risk of urinary secretions decreased with the improvement of education level(P＜0.05).Diagnosed diabetes,use of analgesics(ibuprofen/butazon/indola,etc.),heavy dietary taste was(like to eat pickled/smoked/fried/spicy food),long-term heavy physical work(carrying heavy objects/digging/clearing snow/chopping wood,etc.),and sleep time＜8 h were the risk factors of these four urinary symptoms(P＜0.05).Long-term drinking was a risk factor for frequent urination/urgent urination/painful urination symptoms(OR=1.02,P＜0.05).Conclusion:Personal characteristics,diabetes mellitus,dietary habits,medication history and physical activity have a certain influence on the occurrence of urinary system symptoms.

Objective To study the correlation between the characteristics of tympanic membrane perforation and hearing loss in chronic suppurative otitis media.Methods Ear fibreoptic endoscopic images and complete audio-logical data of 80 patients(104 ears)diagnosed with chronic suppurative otitis media and treated with tympanoplasty type Ⅰ surgery at the Department of Otorhinolaryngology-Head and Neck Surgery of the Second Hospital of Lanzhou University from July 2022 to July 2023 were reviewed.The area of tympanic membrane perforation was measured u-sing ImageJ software.Qualitative variables were professionally assessed by a senior practitioner in otology,inclu-ding whether the perforation involved the quadrant,whether the edge of the perforation was calcified,and whether the extent of the perforation involved the malleus.Results There was a significant positive correlation between the area of tympanic membrane perforation and the mean air-bone conductance difference in patients with tympanic mem-brane perforation due to chronic suppurative otitis media(R2=0.141,P＜0.001).The patients with perforation in-volving the malleus handle had a greater air-bone conductance difference than those without malleus handle involve-ment(P＜0.05).The effect of calcification at the edge of the tympanic membrane perforation and the location of the perforation on hearing loss was minimal and almost negligible.Conclusion Conductive hearing loss due to tympanic membrane perforation is related to the size of the perforation and whether or not the perforation involves the malleus handle,and the patients with larger perforation as well as those with perforations involving the handle of malleus tend to exhibit worse conductive hearing loss.

Objective:To explore the specific role and molecular mechanism of octamer-binding transcription factor 4 (Oct4) in promoting the progression of esophageal squamous cell carcinoma and radioresistance.Methods:The Gene Expression Profile Data Dynamic Analysis (GEPIA) database was used to analyze the expression differences of the Oct4 gene in different types of tumor tissues and their corresponding adjacent normal tissues. The clinical data and surgical resection tissue specimens of 196 patients with esophageal squamous cell carcinoma who received surgery combined with radiotherapy at Henan Provincial Chest Hospital from January 2013 to May 2022 were collected. Immunohistochemistry was used to detect the expression of Oct4 protein in the tumor and adjacent tissues. The lentiviral packaging system was used to construct esophageal squamous cell carcinoma cell lines that up-regulated or down-regulated Oct4. The cell counting kit 8 (CCK-8) was used to detect the cell proliferation ability, the scratch test was used to detect the cell migration ability, and the clone formation test was used to detect the cell radiosensitivity. Immunofluorescence experiment was used to detect DNA damage level, and Western blot was used to detect the expressions of Oct4, human phosphorylated histone (γ-H2AX), E-cadherin, N-cadherin, vimentin, and zinc finger E box binding homology box 1 (ZEB1).Results:The analysis of GEPIA database showed that the expression level of Oct4 mRNA in esophageal carcinoma was higher than that in paracancerous tissues. The expression level of Oct4 protein in tumor tissues was 78.35±1.42, which was higher than that in adjacent tissues (16.27±0.49). The survival time of patients with a high expression of Oct4 was significantly shorter than that of patients with a low expression of Oct4 (25.40 and 47.00 months). Compared with the control group, the proliferation ability of KYSE510 cells in the Oct4 up-regulated group was enhanced after 72-h culture, and the cell migration ability of these cells was also enhanced, with the migration rate being (41.67±1.20)% vs (23.67±1.86)% after 24-h culture. The radiosensitivity of cells in this group decreased, with the radiosensitivity enhancement ratio being 0.69±0.06 vs 1.00±0.02. After radiotherapy, the expressions of γ-H2AX and E-cadherin decreased, while the expressions of ZEB1, vimentin and N-cadherin increased. Compared with the control group, the proliferation ability of KYSE150 cells in the Oct4 down-regulated groups 1 and 2 decreased (absorbance being 2.51±0.17, 2.38±0.16, and 3.33±0.07, respectively, P＜0.01) after 72-h culture, and the migration ability also decreased, with the migration rate being (13.33±0.88)%, (13.00±1.00)%, and (40.33±2.03)%, respectively (all P＜0.001), after 24-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.34±0.11,1.24±0.07, and 1.00±0.02, respectively (all P＜0.05). After radiotherapy, the expressions of γ-H2AX and E-cadherin increased, while the expressions of ZEB1, vimentin and N-cadherin decreased. Compared with the control group, the proliferation ability of KYSE510 cells in the ZEB1 down-regulated group decreased [absorbance being 1.33±0.15 vs 1.81±0.16 ( P=0.002)] after 72-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.37±0.11 vs 1.00±0.01 ( P=0.037), and after radiotherapy the expression of γ-H2AX increased. Conclusion:Oct4 is involved in the regulation of epithelial-mesenchymal transformation of esophageal squamous cell carcinoma, which promotes the proliferation, migration, and radioresistance of esophageal squamous cell carcinoma.