Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

Objective:To retrospectively analyze the results of auditory examination,vestibular function examination and laboratory examination of 63 patients diagnosed as vestibular neuritis.Methods:A total of 63 patients diagnosed with vestibular neuritis hospitalized in the Department of Otolaryngology, Head and Neck Surgery of the Third Affiliated Hospital of Sun Yat-sen University, from October 2012 to December 2022 were recruited. All patients met the diagnostic criteria for the 2022 Bárány association vestibular neuritis. Clinical data and the results of pure tone audiometry, electrocochleogram, video electronystagmogram, caloric test, cervical vestibuloevoked myogenic potential（cVEMP）, ocular vestibuloevoked myogenic potential（oVEMP）, video head impulse test（vHIT） was collected.A total of 63 age-and sex-matched healthy subjects in the physical examination center were randomly selected as the control group. The differences of blood indexs and lipid metabolism indexes between the two groups were compared. Results:In patients with vestibular neuritis, 50 out of 63 patients presented normal threshold in pure tone audiometry, 8 out of 63 patients had bilateral high-frequency sensorineural hearing loss and 5 out of 63 patients had unilateral mild high-frequency sensorineural hearing loss, 56 out of 63 cases completed the electrocochleogram, of which 3 cases had a binaural-SP/AP amplitude ratio≥0.4, 5 cases had monaural amplitude ratio ≥0.4. Fifty-five out of 63 patients completed the caloric test with CP values greater than 30% in all. The ratio of patients completed cVEMP, oVEMP and vHIT were 46 cases, 22 cases and 30 cases, respectively. 17 out of 63 cases completed all the four vestibular function tests. According to these tests, 49 patients could determine the extent of injury，including 27 cases with unilateral superior vestibular nerve injury, 21 cases with unilateral superior and inferior vestibular nerve injury and 1 case with unilateral inferior vestibular nerve injury. There were significant differences in neutrophil value（P<0.001）, lymphocyte value（P<0.005）, neutrophil/lymphocyte ratio（P<0.001） and apolipoprotein A1（P<0.001） between patient group and control group. Inflammatory markers were risk factors for patients with vestibular neuritis. The OR values of neutrophil value and blood neutrophil/lymphocyte ratio were 1.81（1.38-2.37, P<0.001） and 2.11（1.41-3.16, P<0.001）, respectively. Apolipoprotein A1 was a protective factor for patients with vestibular neuritis, and the OR value was 0.004（0.001-0.042, P<0.001）. Conclusion:Electrocochleogram could be used in vestibular neuritis patients with normal pure tone threshold to test whether there is hidden hearing loss in these patients. Neutrophil value, lymphocyte value, neutrophil/lymphocyte ratio and apolipoprotein A1 were correlated with vestibular neuritis. The Neutrophil value and neutrophil/lymphocyte ratio were risk factors for morbidity.
Humans ; Vestibular Neuronitis/physiopathology* ; Retrospective Studies ; Female ; Male ; Audiometry, Pure-Tone ; Hearing Loss, Sensorineural/physiopathology* ; Middle Aged ; Adult ; Vestibular Function Tests ; Vestibular Evoked Myogenic Potentials ; Aged

ObjectiveTo investigate the improvement effect of Qibai Pingfei capsules on pulmonary vascular remodeling in rats at different stages of chronic obstructive pulmonary disease （COPD） and to analyze its possible mechanism of action. MethodsMale Sprague-Dawley （SD） rats were randomly divided into a normal group， an early COPD model group， an advanced COPD model group， an early-intervention high-dose group， a late-intervention high-dose group， an early-intervention low-dose group， a late-intervention low-dose group， an early-intervention pyrrolidine dithiocarbamate （PDTC） group， and a late-intervention PDTC group， with 15 rats in each group. A rat model of early COPD was constructed by using cigarette smoke combined with airway infusion using lipopolysaccharide（LPS）， and a rat model of advanced COPD was constructed by using airway infusion with LPS， cigarette smoke， and hypoxia. All groups except the normal group were given LPS airway drops on days 1 and 14 of the experiment， smoked for 1 h per day， and administered the drug once a day for 40 weeks from day 15 onward. In the high- and low-dose groups， rats were given 1 g·kg^-1 and 250 mg·kg^-1 Qibai Pingfei capsules， respectively by gavage， and in PDTC groups， rats were given 100 mg·kg^-1 of PDTC by intraperitoneal injection. The advanced COPD model group underwent 6 h of hypoxia per day in weeks 5-6. Lung function and mean pulmonary artery pressure were tested in rats. Morphologic changes in lung tissues were detected by hematoxylin-eosin（HE）staining. Collagen deposition in lung tissues was examined by Masson staining， and the levels of inflammatory factors including interleukin-1β（IL-1β）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α）in lung tissues were detected by enzyme-linked immunosorbent assay （ELISA）. The number of inflammatory cells in the alveolar lavage fluid of rats in each group was detected by Giemsa staining， and the protein expression of Toll-like receptor 4（TLR4）， myeloid differentiation factor 88（MyD88）， nuclear factor-κB（NF-κB）， TNF-α， vascular endothelial-cadherin（VE-cadherin）， α-smooth muscle actin（α-SMA）， and platelet endothelial cell adhesion molecule-1（CD31） was detected by Western blot in the lung tissues of rats. ResultsCompared with the normal group， the model group showed significantly decreased forced expiratory volume in 0.3 s （FEV_0.3）， forced vital capacity （FVC）， and FEV_0.3/FVC ratio related to lung function （P<0.05）， thickening of pulmonary vasculature， increased collagen deposition in the lungs， and enhanced mean pulmonary arterial pressure and expression levels of IL-6， IL-1β， and TNF-α （P<0.05）. Additionally， the model group also exhibited increased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， significantly higher protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05）， and significantly lower protein expression of VE-cadherin and CD31 （P<0.05）. Lung function was significantly improved in the Qibai Pingfei capsules groups compared with the model group （P<0.05）， with mean pulmonary arterial pressure reduced and pulmonary vascular thickening and collagen deposition in the lungs ameliorated. The Qibai Pingfei capsules groups also showed reduced expression levels of IL-6， IL-1β， and TNF-α （P<0.05） and decreased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， as well as reduced protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05） and elevated protein expression of VE-cadherin and CD31 （P<0.05） in rat lung tissues. ConclusionQibai Pingfei capsules inhibits inflammatory response and endothelial-to-mesenchymal transition probably by regulating the TLR4/NF-κB signaling pathway， thus improving pulmonary vascular remodeling in COPD model rats and showing therapeutic effects in the early stage of COPD.

Cancer is a group of chronic diseases caused by a combination of genetic and environmental factors.Immune cells play a vital role in the regulation of tumor diseases.Recently,innate lymphoid cells(ILCs)have been found to have an important regu-latory role in the tumor microenvironment.ILCs are tissue resident immune cells located mainly in the mucosa and first barrier organs and have been extensively studied for defense against pathogenic invasion,lymphatic development and tissue repair.The role of ILCs in tumor immunity has received increasing attention in recent years.Among the various subpopulations of ILCs cells,the regulation of ILC3s in tumor immunity is the most controversial.Therefore,we summarized the role of ILC3s in tumor immunity by combining rele-vant studies on the involvement of ILC3s in tumor immune regulation in recent years.

Objective:To understand the status of intestinal helminth infections in Lunan area of Shandong Province (Jining City, Rizhao City, Linyi City, Heze City, and Zaozhuang City), and provide scientific basis for formulating parasitic disease prevention and control strategies.Methods:From 2016 to 2023, a stratified sampling method was used to conduct surveillance in 33 counties (cities, districts, hereinafter referred to as counties) in Lunan area of Shandong Province. Each county was divided into five areas (east, south, west, north, and center), with one administrative village (community) selected from each area. And ≥200 permanent residents (aged ≥3 years old, having lived locally for ≥6 months) were sampled from each village (community), and one stool sample was collected from each participant. The Kato-Katz method (two slides per sample) was used for parasite detection, and the results were analyzed.Results:From 2016 to 2023, a total of 49 436 people were surveyed, including 23 861 males and 25 575 females, with an age range of 3 - 105 years old. The testing identified 687 intestinal helminth infections, with an overall infection rate of 1.39%. The predominant infection was whipworm (582 cases), with an infection rate of 1.18%; followed by roundworm and hookworm, with infection rates of 0.13% (62 cases) and 0.05% (23 cases) respectively; other types of helminths ( Clonorchis sinensis and pinworm) totaled 20 cases, with an infection rate of 0.04%. From 2016 to 2023, the annual intestinal helminth infection rates were 2.76% (201/7 292), 0.90% (56/6 327), 0.84% (52/6 200), 1.70% (124/7 282), 1.23% (88/7 133), 1.45% (104/7 150), 0.34% (17/5 058), and 1.46% (45/3 084), showing an overall downward trend (χ 2trend = 42.40, P < 0.001). The ≥60 age group had the highest intestinal helminth infection rate (2.39%, 323/13 489), while the 30 - 39 age group had the lowest rate (0.68%, 48/7 016). There was statistically significant difference in infection rates among different age groups (χ 2 = 172.25, P < 0.001). There was no statistically significant difference in infection rates between genders (χ 2 = 0.03, P = 0.862). Farmers had the highest infection rate (1.69%, 560/33 118), with statistically significant differences among different occupational groups (χ 2 = 64.88, P < 0.001). Those with primary school education or below had the highest infection rate (1.82%, 445/24 469), with statistically significant differences among different education levels (χ 2 = 64.93, P < 0.001). Conclusions:In Lunan area of Shandong Province, whipworm is the predominant intestinal helminth infection, with elderly people being the high-risk group. Although the intestinal helminth infection rate in this region remains at a low level, there is still a risk of transmission. Continuous surveillance is needed, along with strengthened prevention and control measures for key populations.

Objective:To explore the role of fibroblast growth factor 21 (FGF21) in rats with severe acute pancreatitis-associated acute lung injury (SAP-ALI) and its related molecular mechanisms.Methods:Twenty-four healthy male SD rats were randomly divided into 4 groups (random number, n=6 per group): Control group, SAP group, FGF21 intervention group (SAP+FGF21 group), and autophagy inhibitor group (SAP+FGF21+3-MA group). The SAP model was established by retrograde injection of 3.5% sodium taurocholate into the pancreatic duct. In SAP+FGF21 group, FGF21 10 mg/kg was intraperitoneally injected at 1 hour before modeling. In SAP+FGF21+3-MA group, FGF21 10 mg/kg and 3-MA 20 mg/kg were intraperitoneally injected at 1 h before modeling. Serum amylase activity was detected by biochemical kit. Plasma levels of tumor necrosis factor alpha (TNF-α) and FGF21 were detected by ELISA. HE staining was used to observe the pathological changes of pancreas and lung tissues. Immunofluorescence was used to detect the protein level of FGF21 in lung tissue. Western blot was used to detect the expression levels of autophagy-related proteins in lung tissue. Autophagosomes in lung tissue were observed by electron microscopy. Results:Compared with the Control group, the plasma and lung tissue FGF21 levels in SAP group were significantly decreased (both P<0.001) , severe pancreatic and lung tissue damage, and elevated plasma TNF-α levels ( P<0.001). Western Blot and transmission electron microscopy showed that: The expression of LC3Ⅱ/Ⅰ in lung tissue of SAP group was down-regulated [(0.912±0.052) vs. (0.700±0.135), P<0.001], and P62 protein level was up-regulated [(0.475±0.068) vs. (0.687±0.070), P<0.001] , and reduced autophagosome counts in the SAP group. In contrast, the SAP+FGF21 group showed elevated FGF21 levels (both P<0.01), attenuated pancreatic and lung injury ( P<0.001), decreased TNF-α levels [(280.10±49.36) pg/mL vs. (86.32±66.00) pg/mL, P<0.001]. Lung tissue of LC3 Ⅱ/Ⅰ levels increase [(0.700±0.135) vs. (0.853±0.073), P<0.01], P62 protein levels cut [(0.687±0.070) vs. (0.538±0.030), P<0.01] ], and increased autophagosomes and autolysosomes under electron microscopy. Compared with SAP+FGF21 group, the expression levels of FGF21 in plasma and lung tissue in SAP+FGF21+3-MA group were not significantly changed, and the level of autophagy was decreased. Pancreas and lung tissue injury was severe ( P<0.001), Plasma TNF-α level obviously higher [(86.32±66.00) pg/mL vs. (212.90±11.56) pg/mL, P<0.05]. Conclusion:FGF21 may play a protective role in SAP-ALI by up-regulating the level of autophagy.

Objective:To investigate the factors influencing the delayed onset of intrapartum fever following epidural labor analgesia and their impact on maternal and neonatal outcomes.Methods:Select parturients who experienced intrapartum fever following labor analgesia(T≥38.0℃,age≥18 years,singleton pregnancy,ASA classification Ⅱ)between January 1,2021,and December 31,2023.Group them based on the median time of intra-partum fever onset after labor analgesia:those with onset times less than the median were classified as the ear-ly-onset fever group,and those with onset times greater than the median were classified as the late-onset fever group.Using univariate and multivariate Logistic regression analysis to explore factors influencing the delay in in-trapartum fever onset and the pregnancy outcomes of the mothers and newborns in both groups.Results:A total of 253 parturients were included,and the time range of onset of intrapartum fever following epidural labor analgesi-a was 1.83-28.42 hours,with a median fever onset time of 8.00 hours.There were 126 cases in the early-onset group and 127 in the late-onset group.Multivariate Logistic regression analysis indicated that primiparous women,artificial membrane rupture,and neonatal birth weight were independent risk factors for delayed fever onset(OR＞1,P＜0.05),whereas the administration of oxytocin prior to labor analgesia was found to be a protective factor(OR＜1,P＜0.05).The late-onset group exhibited higher levels of white blood cells(WBC),C-reactive pro-tein,longer hospital stays,higher hospitalization costs,greater diagnosis rates of chorioamnionitis,higher NICU ad-mission rates,as well as a higher incidence of neonatal pneumonia,for newborns compared to the early-onset group(P＜0.05).Conclusions:Primiparous women,artificial membrane rupture,and higher neonatal birth weight may be associated with delayed onset of intrapartum fever,while oxytocin administration prior to labor analgesia may offer some protective benefit.The later the onset of intrapartum fever,the worse the clinical outcomes for both mother and infants.

Objective:To evaluate the clinical utility of machine learning model based radiomics in predicting high-risk molecular subtypes of lower-grade gliomas(LrGGs).Methods:This was a cross-sectional study. A total of 287 patients diagnosed with LrGGs in the First Hospital of Shanxi Medical University, Shanxi Provincial People′s Hospital, and the Third Hospital of Shanxi Medical University from January 2011 to September 2023 were retrospectively collected, including 166 males and 121 females; 114 cases of high-risk molecular subtypes and 173 cases of non-high-risk molecular subtypes. All patients were divided into 201 cases in the training set and 86 cases in the test set according to 7∶3 in simple randomized grouping method. All patients underwent contrast-enhanced T 1WI (CE-T 1WI) and T 2-weighted fluid-attenuated inversion recovery sequence imaging (T 2-FLAIR), and the imaging features of high-risk and non-high-risk molecular subtypes were analyzed. Analysis of variance, recursive feature elimination, and Kruskal-Wallis were used for radiomics feature screening, and a support vector machine (SVM) classifier was used to construct a radiomics-based classifier model. Univariate and multivariate logistic regression were used to analyze clinical variables independently influencing high-risk molecular subtypes of LrGGs to construct a clinical model; a combined model was developed by integrating radiomics labels and clinical variables. Receiver operating characteristic curve and area under the curve (AUC), calibration curve, and decision curve were used to compare the predictive performance of different models. Results:The patient′s age ( OR=1.042, 95% CI 1.018-1.068, P=0.001), pathological grade ( OR=2.270, 95% CI 1.212-4.311, P=0.011), MGMT methylation status ( OR=0.456, 95% CI 0.238-0.866, P=0.017), and ependymal involvement ( OR=7.335, 95% CI 2.929-18.370, P<0.001) were independent influencing factors for the high-risk molecular subtype of LrGGs, and a clinical model was developed based on these factors. An SVM model was constructed based on 12 radiomics features (3 radiomics features based on CE-T 1WI and 9 radiomics features based on T 2-FLAIR). The radiomics score of the probability output by the SVM model was combined with age, pathological grade, MGMT methylation status, and ependymal involvement to develop a combined model. The AUC values of the SVM model for predicting the high-risk molecular subtype of LrGGs were 0.824 and 0.859 in the training set and test set, respectively; the AUC values of the clinical model in the training set and test set were 0.759 and 0.721, respectively; and the AUC values of the combined model in the training set and test set were 0.823 and 0.815, respectively. The combined model had a high clinical net benefit. Conclusion:The machine learning MRI radiomics model can preoperatively predict high risk molecular subtypes of LGGrs, assist in individualized treatment decisions.

Objective:To compare the outcomes of ranibizumab and conbercept adjunct for pars plana vitrectomy (PPV) in the treatment of proliferative diabetic retinopathy (PDR).Methods:A prospective randomized case-control study. From June 2022 to December 2023, 90 cases (90 eyes) of PDR patients diagnosed through ophthalmic examination at Department of Ophthalmology of Gansu Provincial Hospital were included in the study. All patients underwent the best corrected visual acuity (BCVA), intraocular pressure, B-mode ultrasound, and optical coherence tomography (OCT) examinations. The central macular thickness (CMT) was measured using an OCT instrument. The patients were randomly divided into a intravitreal injection of ranibizumab group (monoclonal-antibody group) and a intravitreal injection of conbercept group (fusion-protein group) using a random number table method, with 45 cases (45 eyes) in each group. Two groups of patients were intravitreal injected with 10 mg/ml ranibizumab or conbercept 0.05 ml, respectively. A standard 23G PPV was performed through the flat part of the ciliary body 3-7 days after intravitreal injection. Relevant examinations were performed using the same equipments and methods as before surgery at postoperative 1 week, 1, 3, 6, and 12 months. The PPV time, intraoperative use of intraocular electrocoagulation, incidence of iatrogenic retinal breaks, and sterile air or silicone oil tamponade rate in the vitreous cavity, the postoperative changes of BCVA and CMT, and incidence of complications were compared between two groups. Independent sample t test was used for inter group comparison. Results:The intraoperative utilization rate of intraocular electrocoagulation in the monoclonal-antibody group was higher than that in the fusion-protein group, and the difference was statistically significant ( χ2=3.876, P<0.05). There were no statistically significant differences in the PPV time ( t=0.152), intraoperative bleeding rate ( χ2=0.800), incidence of iatrogenic retinal breaks ( χ2=1.975), and sterile air and silicone oil tamponade rate in the vitreous cavity ( χ2=1.607, 1.553) between the two groups ( P>0.05). There were no statistically significant differences in early and late postoperative vitreous hemorrhage ( χ2=1.235, 2.355), and re-PPV ( χ2=2.355) between two groups ( P>0.05). The BCVA of the fusion-protein group was significantly better than that of the monoclonal-antibody group at postoperative 3 months, and the difference was statistically significant ( t=2.428, P<0.05). The CMT of the fusion-protein group was lower than that in the monoclonal-antibody group at postoperative 1 week, and the difference was statistically significant ( t=2.739, P<0.05). None of the patients experienced endophthalmitis, retinal artery occlusion, or severe cardiovascular events after surgery. Conclusion:Compared with intravitreal injection of ranibizumab before PPV, intravitreal injection of conbercept before PPV in PDR patients can shorten the surgical time, reduce intraoperative bleeding rate, lower the rate of electrocoagulation and intraocular tamponade, and incidence of iatrogenic retinal breaks, and improve the visual acuity.

OBJECTIVE To analyze the direct economic burden associated with carbapenem-resistant gram-negative bacteria(CRGNB)infections during hospitalization,and to provide reference for relevant policy formulation.METHODS Basic information including ICU admission,International Classification of Diseases(ICD)codes and CRGNB infection of intensive care unit(ICU)inpatients from Sanya Central Hospital(the Third People's Hospi-tal of Hainan Province)in the southern Hainan region from 2019 to 2023 was collected for risk factor analysis.Propensity matching was performed between the CRGNB infection and non-infection subgroups,and the direct economic differences between the two groups were analyzed.RESULTS A total of 164 373 cases were includ-ed.Multifactor logistic regression analysis revealed that ICD codes F00-F99,G00-G99,I00-I99,J00-J99,L00-L99,N00-N99,P00-P96 and S00-T98,ICU admission,hospital-acquired infection,readmission within 90 days and hospitalization exceeding 7 days were risk factors for CRGNB infection,especially,codes J00-J99(respiratory system diseases)were 7.68 to 17.47 folds higer than codes C00-D48(tumors).In the direct economic analysis of CRGNB infection,different matching results yielded consistent findings.In the 1∶1 matching results,a compari-son of total hospitalization costs(yuan)between different groups showed that the infection group had higher total hospitalization costs than the non-infection group.The costs were as follows:CRGNB group(88 421.40 vs.32 475.56),subgroup with two or more CRGNB types(130 984.02 vs.47 367.27),group with CRGNB and oth-er multidrug-resistant bacteria(103 056.35 vs.37 724.78),CRAB group(98 486.01 vs.36 487.98),and CRE group(26 031.38 vs.17 621.82).CONCLUSIONS The direct economic burden of CRGNB infection is greater than that of the non-infection group.Among them,the direct economic burden of carbapenem-resistant gram-negative bacteria infection,carbapenem-resistant gram-negative bacteria co-infected with other multidrug-resistant bacteria and CRAB infection are the highest.