ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

AIM To investigate the clinical effects of Cinobufosin Injection combined with RALOX-HAIC regimen on patients with hepatocellular carcinoma.METHODS Ninety-two patients were randomly assigned into control group(46 cases)for intervention of RALOX-HAIC regimen,and observation group(46 cases)for intervention of both Cinobufosin Injection and RALOX-HAIC regimen.The changes in short-term effects,survival situation,inflammatory indices(LCN2,NLRP3 inflammasome,NLR,PLR),immune indices(NK cells,CD8+T cells,IL-17,Th17/Treg)and incidence of toxic and side effects were detected.RESULTS Based on mRECIST,the observation group demonstrated higher disease control rate and objective remission rate than the control group(P＜0.05),along with lower disease progression(P＜0.05).After the treatment,the two groups displayed decreased inflammatory indices,IL-17,Th17/Treg(P＜0.05),and increased NK cells,CD8+T cells(P＜0.05),especially for the observation group(P＜0.05).The observation group exhibited lower incidence of abdominal pain,nausea,vomiting,diarrhea,leukopenia and thrombocytopenia than the control group(P＜0.05),and no significant differences in overall survival and incidence of other toxic and side effects were found between the two groups(P＞0.05).CONCLUSION For the patients with hepatocellular carcinoma,Cinobufosin Injection combined with RALOX-HAIC regimen can safely and effectively enhance body immune functions,and reduce in vivo immune indices.

Objective:To establish an identical UPLC-MS/MS method for determination of related substances of 15 drugs(bezafibrate,acipimox,gliquidone,glimepiride,glipizide,glibenclamide,enalapril,captopril,irbesartan,amlodipine,felodipine,nimodipine,nitrendipine,nisoldipine,nifedipine).Methods:The chromatography was performed on Waters ACQUITY UPLCHSS T3(2.1 mm × 100 mm,1.8 μm)column,mobile phase was 0.01 mmol·L-1 Ammonium formate solution containing 0.1％formic acid and methanol with gradient elution.The flow rate was 0.3 mL·min-1,and the injection volume was 2 μL.The detection was carried out by electrospray ioniza-tion(ESI).Multiple-reaction monitoring(MRM)was employed with switching electrospray ion source polarity in positive and negative mode.Results:The 21 related substances showed good linearity(r ≥0.998 35)in the tested ranges.The precision(RS D≤3.45％)and stability(RSD≤3.48％)of the method were good for the related sub-stances.The average recoveries of the related substances were in the range of 91.81％-101.84％with relative standard deviations RSD≤4.66％.Conclusion:The method is rapid,simple,accurate and highly sensitive,and can be used as a auxiliary test method and confirmatory method for current drug standards.

Objective:To establish an identical UPLC-MS/MS method for determination of related substances of 15 drugs(bezafibrate,acipimox,gliquidone,glimepiride,glipizide,glibenclamide,enalapril,captopril,irbesartan,amlodipine,felodipine,nimodipine,nitrendipine,nisoldipine,nifedipine).Methods:The chromatography was performed on Waters ACQUITY UPLCHSS T3(2.1 mm × 100 mm,1.8 μm)column,mobile phase was 0.01 mmol·L-1 Ammonium formate solution containing 0.1％formic acid and methanol with gradient elution.The flow rate was 0.3 mL·min-1,and the injection volume was 2 μL.The detection was carried out by electrospray ioniza-tion(ESI).Multiple-reaction monitoring(MRM)was employed with switching electrospray ion source polarity in positive and negative mode.Results:The 21 related substances showed good linearity(r ≥0.998 35)in the tested ranges.The precision(RS D≤3.45％)and stability(RSD≤3.48％)of the method were good for the related sub-stances.The average recoveries of the related substances were in the range of 91.81％-101.84％with relative standard deviations RSD≤4.66％.Conclusion:The method is rapid,simple,accurate and highly sensitive,and can be used as a auxiliary test method and confirmatory method for current drug standards.

BACKGROUND:Immune cells are correlated with various metabolic bone diseases,yet the specific immunological mechanisms and causal relationships remain elusive.OBJECTIVE:To investigate the causal relationship between immune cells and the risk of metabolic bone diseases through two-sample Mendelian randomization.METHODS:Genome-wide association study(GWAS)data on 731 immune cells and metabolic bone diseases(osteonecrosis,osteomalacia,osteoporosis,and osteoporosis combined with pathological fracture)were obtained from publicly available databases.Genetic variants related to immune cells were employed as instrumental variables.The inverse variance weighting method was utilized as the primary analytical approach,while MR-Egger and weighted median methods were applied to assess the causal relationships between immune cells and the risk of metabolic bone diseases.In addition,MR-PRESSO,MR-Egger regression,Cochran's Q test,and the leave-one-out method were implemented to evaluate genetic polymorphisms and the heterogeneity of instrumental variables,and MR Steiger method was used to exclude reverse causality.RESULTS AND CONCLUSION:(1)The analysis revealed that IgD-CD38dim％B cells,HLA DR on CD14+CD16-monocytes,and HLA DR on CD14+monocytes were significantly and causally associated with an increased risk of osteoporosis(P＜6.8x10-5).Sensitivity analyses confirmed the reliability and stability of these results.Furthermore,among the immune cell types studied,28 demonstrated potential causal associations with osteonecrosis,23 with osteomalacia,46 with osteoporosis,and 45 with the combined condition of osteoporosis and pathologic fracture(P＜0.05).(2)This study provides a comprehensive assessment of the causal influence of immune cells on metabolic bone diseases,highlighting the significant role of immune factors in the pathogenesis of these conditions,particularly osteoporosis.The findings contribute valuable insights into the relationship between immune traits and bone metabolism,laying a foundation for future research in this domain.This study utilized an international database to analyze the European population,which offers a reference for Chinese biomedical research in the realm of metabolic bone diseases,and facilitates the conduction of relevant studies for the Chinese population,thereby promoting the enhancement of the prevention and treatment of metabolic bone diseases.

Purpose To explore the clinical and imaging characteristics of central nervous system candidiasis due to Candida albicans in immunocompetent infants children.Materials and Methods A retrospective analysis was conducted on immunocompetent children with central nervous system candidiasis diagnosed at Beijing Children's Hospital,Capital Medical University from October 2012 to October 2022,and their clinical and MRI characteristics were analyzed.Results Among the 26 enrolled children,88.5%(23 cases)were under one year old,and 88.5%(23 cases)had high-risk factors.Premature birth was the most common high-risk factor(16 cases,61.5%).All 26 cases had positive MRI examinations,with the main manifestations being meningeal thickening and enhancement(25 cases,96.2%),57.7%(15 cases)involving the skull base meninges,23.1%(six cases)involving the cranial nerves,intracranial localized granulomas(16 cases,61.5%),hydrocephalus(14 cases,53.8%),cerebral infarction(four cases,15.4%),subdural effusion(six cases,23.1%)and cerebral abscess(two cases,7.7%);13 cases of magnetic resonance angiography and magnetic resonance venography examinations were performed,and 10 cases of magnetic resonance angiography abnormalities were found,mainly due to thinning,narrowing or reduced branches of the arterial trunk,and one case of magnetic resonance venography transverse sinus thrombosis.Conclusion Central nervous system candidiasis mostly exists in children younger than one year old.MR imaging shows a more characteristic invasion of the skull base,often causing enhancement of the skull base meninges and cranial nerves,as well as localized granulomas and hydrocephalus.Imaging examination is of great significance for early diagnosis.

Purpose To explore the clinical and imaging characteristics of central nervous system candidiasis due to Candida albicans in immunocompetent infants children.Materials and Methods A retrospective analysis was conducted on immunocompetent children with central nervous system candidiasis diagnosed at Beijing Children's Hospital,Capital Medical University from October 2012 to October 2022,and their clinical and MRI characteristics were analyzed.Results Among the 26 enrolled children,88.5%(23 cases)were under one year old,and 88.5%(23 cases)had high-risk factors.Premature birth was the most common high-risk factor(16 cases,61.5%).All 26 cases had positive MRI examinations,with the main manifestations being meningeal thickening and enhancement(25 cases,96.2%),57.7%(15 cases)involving the skull base meninges,23.1%(six cases)involving the cranial nerves,intracranial localized granulomas(16 cases,61.5%),hydrocephalus(14 cases,53.8%),cerebral infarction(four cases,15.4%),subdural effusion(six cases,23.1%)and cerebral abscess(two cases,7.7%);13 cases of magnetic resonance angiography and magnetic resonance venography examinations were performed,and 10 cases of magnetic resonance angiography abnormalities were found,mainly due to thinning,narrowing or reduced branches of the arterial trunk,and one case of magnetic resonance venography transverse sinus thrombosis.Conclusion Central nervous system candidiasis mostly exists in children younger than one year old.MR imaging shows a more characteristic invasion of the skull base,often causing enhancement of the skull base meninges and cranial nerves,as well as localized granulomas and hydrocephalus.Imaging examination is of great significance for early diagnosis.

Objective:To investigate the effects of thoracolumbar vertebral fracture with incomplete spinal cord injury on male sexual function and postoperative prognosis.Methods:A retrospective review was conducted on data from 144 male patients with thoracolumbar vertebral fractures and incomplete spinal cord injuries treated between May 2009 and May 2021 in the Department of Traumatology and Orthopedics at Peking University Third Hospital. Patients ranged in age from 19 to 55 years (mean: 38.6±10.6 years) and underwent posterior incision and reduction internal fixation. The International Index of Erectile Function-5 (IIEF-5), the Premature Ejaculation Diagnostic Tool (PEDT), and the International Spinal Cord Injury Male Sexual Function Basic Data Set were used for sexual function evaluation. Based on the American Spinal Injury Association (ASIA) Spinal Cord Injury classification, changes in neurological and sexual function were assessed at the pre-injury stage, 3 months post-injury, 2 years postoperatively, and at the final follow-up. Factors influencing sexual dysfunction and recovery were analyzed. Spearman correlation analysis was used to identify factors affecting sexual function injury and recovery.Results:A total of 117 patients were included in the final analysis. Follow-up duration ranged from 26.2 to 161.7 months (mean: 74.6±40.5 months). After injury, ASIA grades were distributed as follows: 43 patients with grade B, 41 with grade C, and 33 with grade D. At the 2-year follow-up, 30 patients were grade E, 63 grade D, 19 grade C, and 5 grade B. Improvement in ASIA classification was observed in 90.6% (106/117) of patients: 79 improved by one grade, 27 by two grades, 8 remained unchanged, 1 worsened by one grade, and 2 worsened by two grades. Mean IIEF-5 scores were 19.5±6.4 pre-injury, 8.7±8.0 at 3 months post-injury, and 17.5±7.1 at 2 years postoperatively, with statistically significant differences ( F=123.247, P<0.001). Differences between 3 months post-injury vs. pre-injury and 2 years postoperatively vs. 3 months post-injury were statistically significant ( P<0.05). Mean PEDT scores were 5.3±3.1 pre-injury, 6.9±5.2 at 3 months post-injury, and 6.4±5.1 at 2 years postoperatively, with statistically significant differences ( F=17.014, P<0.001). The difference between 3 months post-injury and pre-injury was statistically significant ( P<0.05), but not between 2 years postoperatively and 3 months post-injury ( P>0.05). At the 2-year follow-up, 96 patients had their IIEF-5 classification restored to pre-injury levels, 85 restored PEDT classifications, and 83 restored both. Post-injury ASIA classification was positively correlated with a decrease in IIEF-5 score and an increase in PEDT score at 3 months post-injury ( P<0.05). Injury segment was positively correlated with the decrease in IIEF-5 score ( P<0.05). Time from injury to surgery showed a positive correlation with increased PEDT score at 3 months ( P<0.05). Post-injury ASIA grade, injury segment, time to surgery, age, intraoperative decompression, and spinal cord function recovery all showed significant correlations with changes in IIEF-5 and (or) PEDT scores at 2 years postoperatively ( P<0.05). According to the International Spinal Cord Injury Male Sexual Function Basic Data Set, the proportion of patients willing to discuss sexual issues increased from 29.9% at 3 months post-injury to 47.9% at 2 years postoperatively ( P<0.05). The proportion of patients with absent or diminished psychogenic erections remained stable (48.7% vs. 48.9%, P>0.05), while those with normal reflexive erections increased from 34.2% to 65.0% ( P<0.05). Conclusion:Thoracolumbar fractures with incomplete spinal cord injury result in reduced erectile function and increased incidence of premature ejaculation. The degree of spinal cord injury and the level of the injured segment are strongly correlated with the extent of sexual dysfunction. At the 2-year postoperative follow-up, 70.9% of patients had recovered sexual function to pre-injury levels.