AIM:To investigate the effects of high-altitude hypoxic exposure on retinal injury and the associated changes in oxidative stress-related indicators in rats. METHODS: Twenty-four healthy male Sprague-Dawley(SD)rats were randomly divided into a plain group and a high-altitude group, with 12 rats(24 eyes)in each group. Rats in the plain group were housed under normoxic conditions in an SPF-grade animal facility, whereas rats in the high-altitude group were placed in a special environmental chamber simulating an altitude of 6 000 m for 7 d. Optical coherence tomography(OCT)was used to assess retinal layer architecture and quantify retinal thickness. Hematoxylin-eosin(HE)staining was performed to observe retinal histopathological changes. Immunofluorescence(IF)was used to detect the expression of hypoxia-inducible factor-1α(HIF-1α)in retinal tissue. Transmission electron microscopy(TEM)was applied to examine the ultrastructure of retinal ganglion cells(RGCs). Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of malondialdehyde(MDA), total superoxide dismutase(T-SOD), and reduced glutathione(GSH)in retinal tissue. In addition, intracellular reactive oxygen species(ROS)levels in retinal tissue were assessed using the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe. RESULTS: OCT examination revealed disorganized retinal architecture in the high-altitude group, with increased inner and middle ring thickness and decreased outer ring thickness compared with the plain group(all P<0.05). HE staining showed varying degrees of retinal layer damage, blurred layer boundaries, loosely arranged RGCs, and partial cellular necrosis in the high-altitude group. IF analysis demonstrated significantly increased HIF-1α expression in the inner nuclear layer of the high-altitude group(P<0.01). TEM revealed mitochondrial swelling, disrupted cristae, and reduced matrix electron density in RGCs of the high-altitude group. ELISA and fluorescence probe assays showed significantly elevated MDA levels and ROS fluorescence intensity, accompanied by decreased T-SOD and GSH levels in the retinal tissue of the high-altitude group(all P<0.05). CONCLUSION: Exposure to a high-altitude hypoxic environment induces marked morphological and ultrastructural damage in the rat retina and significantly enhances oxidative stress, suggesting that oxidative stress may play a critical role in retinal injury induced by high-altitude hypoxia.

OBJECTIVE To provide reference for medical institutions to establish the record management mode and review rules of off-label use of 5-aminolevulinic acid （ALA） in photodynamic therapy based on the level of evidence. METHODS All ALA-containing outpatient prescriptions in the rational drug use system in our hospital from January 1， 2024 to December 31， 2025 were retrospectively collected. Based on the drug instructions， the current status of off-label use of ALA in photodynamic therapy was identified . The relevant studies in Micromedex， PubMed， CNKI， Wanfang Data and other databases were systematically searched as the relevant evidence-based evidence of ALA off-label use. According to the Off-label Drug Use Filing Standard of the hospital，the evidence-based evaluation method was used to evaluate the evidence-based evidence of ALA off-label use and carry out hierarchical management. RESULTS A total of 1 803 effective prescriptions were included， of which 676 （37.49%） were off-label use， distributed in the dermatology department （564 prescriptions，83.43%） and the plastic surgery department （112 prescriptions，16.57%）. All 676 prescriptions were off-indications medication， involving ten types of skin diseases， primarily including moderate to severe acne （39.94%）， skin warts （25.44%）， Bowen’s disease （11.98%）， and others. According to evidence-based evidence，off-label uses such as moderate to severe acne， actinic keratosis， and Bowen’s disease were managed according to the evidence categoryⅠ orⅡ.The uses of extramammary Paget’s disease and rosacea were managed according to the evidence category Ⅲ.The uses of lichen sclerosus and keloids were managed according to the evidence category Ⅳ.The results of evidence-based evaluation showed that 92.01% of off-label use in our hospital had high-level evidence-based support （ evidence category was gradeⅠ-Ⅱ）. CONCLUSIONS Off-label uses supported by high-level evidence， such as moderate to severe acne， skin warts， and Bowen’s disease， can be managed under filing category Ⅰ or Ⅱ. For the use of lichen sclerosus and keloids， evidence-based evidence is insufficient and should be strictly restricted.The vast majority of ALA off-label use in our hospital has sufficient evidence-based basis.

OBJECTIVE To investigate the protective effect of 2-dodecyl-6-methoxy-2，5-diene-1，4-cyclohexanedione （DMDD）， an active component from Averrhoa carambola root， on myocardial injury in diabetic mice based on the nuclear receptor coactivator 4/ferritin heavy chain 1/autophagy-related protein 8 （NCOA4/FTH1/ATG8） axis. METHODS The successfully modeled diabetic mice were randomly divided into model group and DMDD low-， medium-， and high-dose （12.5， 25， 50 mg/kg） groups， while an additional non-modeled control group was established， with 6 mice in each group. Each group received the corresponding drug solution or an equal volume of normal saline intragastically once daily for 21 consecutive days. After the administration， the levels of fasting blood glucose （FBG）， serum lactate dehydrogenase （LDH）， and creatine kinase isoenzyme MB （CK-MB） were measured. Myocardial pathological changes， degree of fibrosis， and myocardial cell ultrastructure were observed. Myocardial cell death index and NCOA4 protein positive index were detected. The protein expression levels of NCOA4， FTH1， ATG8， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in cardiac tissue were measured. RESULTS Compared with model group， each DMDD group showed significant alleviation of cardiac pathological injury and varying degrees of improvement in the myocardial cell ultrastructure. The FBG and serum LDH and CK-MB levels， the myocardial cell death index and NCOA4 protein positive index，the protein expression levels of NCOA4， FTH1， and ATG8 in cardiac tissue were significantly decreased （ P ＜0.001）， while the protein expression levels of SLC7A11 and GPX4 were significantly increased （ P ＜0.001）. CONCLUSIONS DMDD can reduce blood glucose levels， alleviate myocardial histopathological injury， and inhibit cell death in diabetic mice. The mechanism is associated with inhibiting excessive activation of the NCOA4/FTH1/ATG8 axis and reducing ferritinophagy.

Diabetic Peripheral Neuropathy （DPN） is one of the most common and harmful complications of type 2 diabetes. DPN's pathogenesis include high blood sugar-induced oxidative stress， inflammation， and mitochondrial dysfunction. These factors are combined to damage nerve fibers， leading to sensory issues， pain， and numbness. Through a coordinated effect， these factors trigger nerve fiber damage and lead to sensory abnormalities， pain and numbness in limbs， and other symptoms， seriously restricting patients' activities of daily living and mobility. Recent research highlights that cellular senescence plays a critical role in DPN. Cellular senescence is manifested by the loss of cell proliferation ability， and further aggravates nerve damage via oxidative stress， mitochondrial dysfunction， autophagy impairment， inflammatory reaction， and other mechanisms， accelerating DPN occurrence and progression. In terms of medical treatment， current methods focus on blood sugar control， pain relief medicine， and microcirculation improvement， while no therapy has been developed based on cellular senescence. In contrast， traditional Chinese medicine （TCM） shows a unique advantage in DPN prevention and treatment via cellular senescence modulation. TCM emphasizes a holistic approach， as well as syndrome differentiation and treatment， effective in anti-aging and nerve damage repair. Recent studies show that TCM active ingredients， including puerarin， ginsenosides， and berberine， can reduce inflammation， oxidative stress， and apoptosis via signaling pathway regulation， thereby slowing cellular senescence to alleviate nerve damage. Furthermore， TCM compounds such as Buyang Huanwutang， Taohong Siwutang， and Huangqi Guizhi Wuwutang exert synergistic effects on cellular senescence-related pathways to improve nerve health and reduce DPN clinical symptoms. Therefore， this paper reviews the literature related to the interaction between cellular senescence and DPN from the perspective of cellular senescence， summarizing the mechanism of DPN and TCM intervention strategies.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

Objective:To investigate the iodine nutrition status of children aged 8 - 10 and pregnant women in Xining City, Qinghai Province.Methods:From 2019 to 2021, a stratified cluster sampling method was used to divide 7 counties (districts) under the jurisdiction of Xining City, Qinghai Province into 5 sampling areas according to east, west, south, north, and center each year. One township (town, street) was selected from each area. Forty non boarding students aged 8 to 10 from each primary school (half male and half female, age balanced) and 20 pregnant women from each township (town, street) location were selected to collect edible salt samples at home and a random urine sample to measure salt iodine and urinary iodine level. B-ultrasound was used to measure thyroid volume in children and the goiter rate was calculated.Results:A total of 6 534 samples of household edible salt were collected from children and pregnant women, with an average salt iodine concentration of 25.58 mg/kg. The coverage rate of iodized salt was 97.50% (6 371/6 534), and the qualified iodized salt consumption rate was 89.46% (5 845/6 534). A total of 4 362 urine samples were collected from children, with a median urinary iodine level of 183.10 μg/L. The difference between different years was statistically significant ( H = 20.27, P < 0.001). A total of 2 169 urine samples were collected from pregnant women, with a median urinary iodine level of 168.90 μg/L. The difference between different years was statistically significant ( H = 107.09, P < 0.001). A total of 3 336 cases of thyroid gland examination were conducted in children, including 33 cases of thyroid enlargement, with a goiter rate of 0.99%. There was a statistically significant difference between different years (χ 2 = 15.00, P < 0.001). Conclusion:From 2019 to 2021, children aged 8 to 10 and pregnant women in Xining City are at an appropriate level of iodine, and the achievements in prevention and treatment of iodine deficiency disorders still need to be continuously consolidated.

Objective:To investigate effect and mechanism of Morin on inflammatory response of young asthmatic rats by regu-lating mammalian target of rapamycin(mTOR)/signal transducers and activators of transcription 3(STAT3)signaling pathway.Methods:An asthma rat model was established.Experiment was separated into Control group,Model group,Morin low-dose[Morin-L,10 mg/(kg·d)]group,Morin medium dose[Morin-M,30 mg/(kg·d)]group,Morin high-dose[Morin-H,100 mg/(kg·d)]group and Morin high-dose+mTOR activator group[Morin-H+MHY-1485,100 mg/(kg·d)Morin+7 mg/(kg·d)MHY-1485]group.Enhanced expiratory interval value was detected and recorded;Total IgE,ovalbumin(OVA)specific IgE,IL-4,IL-5,IL-17,IL-13,IFN-γ and TGF-β1 levels were determined by ELISA;Giemsa staining was applied to observe and record situation of related inflammatory cells;proportion of Th1,Th2 and Th17 cells were detected by flow cytometry;HE and PAS staining were applied to observe pathologi-cal changes in lung tissue and goblet cell proliferation;GATA-binding protein 3(GATA-3)expression was detected by immunohisto-chemistry and qRT-PCR;Western blot was applied to detect expression and phosphorylation levels of mTOR and STAT3 proteins.Results:Compared with Control group,inflammatory cell infiltration was obvious in Model group,with irregular thickening of tube wall and basement membrane,obviously more goblet cells,and increased mucus secretion,Penh value,IL-4,IL-5,IL-17,IL-13,total IgE and OVA-sIgE levels,macrophages,lymphocytes,eosinophils and neutrophils numbers,Th2 and Th17 cells proportion,average optical density of GATA-3,GATA-3 mRNA and phosphorylation levels of mTOR and STAT3 were obviously increased(P<0.05),proportion of Th1 cells and IFN-γ level were significantly reduced(P<0.05).Compared with Model group,bronchial wall structure of rats in Morin-L,Morin-M and Morin-H groups was smoother and more complete,with epithelial cells arranged in a more orderly manner,moderate airway wall thickness,reduced inflammatory cell infiltration,and reduced goblet cell proliferation,Penh value,IL-4,IL-5,IL-17,IL-13,TGF-β1,total IgE and OVA-sIgE levels,numbers of macrophages,lymphocytes,eosinophils and neutrophils,proportion of Th2 and Th17 cells,average optical density of GATA-3,GATA-3 mRNA,and phosphorylation levels of mTOR and STAT3 were obviously decreased(P<0.05),proportion of Th1 cells and IFN-γ level were significantly increased(P<0.05).MHY-1485 reversed inhibitory effect of morin on inflammatory response in asthmatic rats(P<0.05).Conclusion:Morin may inhibit activation of mTOR/STAT3 signaling pathway,inhibit inflammatory response in young rats with asthma,and thereby improve asthma symptoms.

Aim To explore the mechanism of Lycium barbarum glycopeptide(LbGP)improving aging in rat primary ovarian granulosa cells.Methods This study divided the cells into a normal group,a DOX group,and four different LbGP concentration treatment groups post-DOX intervention.Results Cell proliferation was assessed using CCK-8,EDU,and Ki67 assays,while aging markers and mitochondrial function-related fac-tors were detected using immunofluorescence and West-ern blotting.The results showed that,compared to the DOX group,LbGP treatment significantly increased cell viability(P＜0.05)and promoted proliferation(P＜0.05).Post LbGP treatment,the β-galactosidase-posi-tive area in cells was significantly reduced compared to the DOX group(P＜0.05).Immunofluorescence re-sults indicated that,compared to the DOX group,levels of p21 and γH2AX significantly decreased(P＜0.05),while pRB increased(P＜0.05)after LbGP treatment.Western blot results showed that,compared to the DOX group,the aging phenotype proteins p21 and p53 significantly decreased(P＜0.05),and pRB notably increased(P＜0.05)in the LbGP treatment group.The release of cytC into the cytoplasm and the activated caspase-9 significantly decreased(P＜0.05);levels of CAMKK2,pAMPK,and mitochondrial calcium homeostasis regulator MCU increased(P＜0.05);nuclear energy metabolism-related proteins SirT1,PGC1α/β and ATP5A1 significantly increased(P＜0.05);compared to the DOX group,ROS levels significantly decreased after LbGP treatment(P＜0.05).Conclusions The results suggest that LbGP can ameliorate DOX-induced aging in rat primary ovar-ian granulosa cells,potentially through the upregulation of the CAMKKβ/AMPK signaling pathway,thereby im-proving mitochondrial calcium homeostasis and increas-ing the expression levels of cell energy metabolism-re-lated regulatory proteins.This provides an experimen-tal basis for LbGP's potential role in supporting the im-provement of ovarian function.