ObjectiveTo investigate the potential mechanisms underlying the therapeutic effects of Bushen Huoxue Formulation （补肾活血方， BSHXF） in Parkinson's disease （PD） from the perspectives of synaptic vesicle cycling and intestinal barrier function. MethodsForty-eight male SD rats were randomly divided into four groups， control group， model group， Madopar group， and BSHXF group， with 12 rats in each group. Except for the control group， rats were administered rotenone by gavage once daily for 4 consecutive weeks to establish a PD rat model. After successful modeling， rats in the BSHXF group received concentrated BSHXF solution by gavage at a dose of 13.5 g/（kg·d）， while rats in the Madopar group received Madopar tablet suspension at 2 g/（kg·d）. Rats in the control group and the model group were administered distilled water by gavage at 10 ml/（kg·d）. All groups received continuous gavage treatment for 2 weeks. Motor function was evaluated using the open field test （total distance traveled， average speed， and total distance traveled in the central zone）， rotarod test （latency to fall）， and balance beam test （traversal time）. Histopathological changes in colon tissues were observed by HE staining. Western Blotting was used to detect the protein levels of α-synuclein （α-syn）， phosphorylated serine 129 α-synuclein （pSer129-α-syn）， vesicle-associated membrane protein 2 （VAMP2）， and synaptophysin （SYP） in the substantia nigra and colon tissues. The mRNA expression levels of α-syn， VAMP2， and SYP were detected by RT-PCR， and α-syn expression was examined by immunohistochemistry. Immunofluorescence staining was performed to assess the levels of tight junction protein 1 （ZO-1） and occludin in colon tissues， as well as tyrosine hydroxylase （TH） levels in substantia nigra tissues. ResultsCompared with the control group， rats in the model group showed reduced total distance traveled， average speed， and central-zone distance in the open field test， decreased latency to fall in the rotarod test， and prolonged traversal time in the balance beam test. The protein levels of pSer129-α-syn and α-syn， as well as α-syn mRNA expression were increased in the substantia nigra and colon tissues， whereas the protein and mRNA expression levels of VAMP2 and SYP were decreased. The relative integrated optical density of α-syn in the substantia nigra and colon tissues was increased， while the relative fluorescence intensities of ZO-1 and occludin in colon tissues and TH in the substantia nigra were decreased （P＜0.05）. HE staining showed focal necrosis in the mucosal layer of colon tissues， disappearance of some intestinal glands， extensive inflammatory cell infiltration， and proliferation of fibrous connective tissue in the submucosa. Compared with the model group， both the Madopar group and BSHXF group showed varying degrees of improvement in the above indicators （P＜0.05）. Pathological damage in colon tissues was also alleviated， with only mild fibrous tissue proliferation and limited diffuse inflammatory cell infiltration observed in the mucosal layer. Compared with the Madopar group， rats in the BSHXF group exhibited increased average speed， central-zone distance， and latency to fall in the rotarod test. The levels of pSer129-α-syn and α-syn proteins in the substantia nigra were decreased， while VAMP2 protein expression was increased. In colon tissues， SYP protein levels and mRNA expression were elevated. The relative fluorescence intensity of ZO-1 in colon tissues and TH in substantia nigra tissues was also increased （P＜0.05）. ConclusionBSHXF may improve motor dysfunction in PD by regulating synaptic vesicle cycling， restoring intestinal barrier integrity， and improving neuronal synaptic function through modulation of synaptic vesicle-associated protein expression in the substantia nigra and colon tissues.

ObjectiveTo investigate the potential mechanisms underlying the therapeutic effects of Bushen Huoxue Formulation （补肾活血方， BSHXF） in Parkinson's disease （PD） from the perspectives of synaptic vesicle cycling and intestinal barrier function. MethodsForty-eight male SD rats were randomly divided into four groups， control group， model group， Madopar group， and BSHXF group， with 12 rats in each group. Except for the control group， rats were administered rotenone by gavage once daily for 4 consecutive weeks to establish a PD rat model. After successful modeling， rats in the BSHXF group received concentrated BSHXF solution by gavage at a dose of 13.5 g/（kg·d）， while rats in the Madopar group received Madopar tablet suspension at 2 g/（kg·d）. Rats in the control group and the model group were administered distilled water by gavage at 10 ml/（kg·d）. All groups received continuous gavage treatment for 2 weeks. Motor function was evaluated using the open field test （total distance traveled， average speed， and total distance traveled in the central zone）， rotarod test （latency to fall）， and balance beam test （traversal time）. Histopathological changes in colon tissues were observed by HE staining. Western Blotting was used to detect the protein levels of α-synuclein （α-syn）， phosphorylated serine 129 α-synuclein （pSer129-α-syn）， vesicle-associated membrane protein 2 （VAMP2）， and synaptophysin （SYP） in the substantia nigra and colon tissues. The mRNA expression levels of α-syn， VAMP2， and SYP were detected by RT-PCR， and α-syn expression was examined by immunohistochemistry. Immunofluorescence staining was performed to assess the levels of tight junction protein 1 （ZO-1） and occludin in colon tissues， as well as tyrosine hydroxylase （TH） levels in substantia nigra tissues. ResultsCompared with the control group， rats in the model group showed reduced total distance traveled， average speed， and central-zone distance in the open field test， decreased latency to fall in the rotarod test， and prolonged traversal time in the balance beam test. The protein levels of pSer129-α-syn and α-syn， as well as α-syn mRNA expression were increased in the substantia nigra and colon tissues， whereas the protein and mRNA expression levels of VAMP2 and SYP were decreased. The relative integrated optical density of α-syn in the substantia nigra and colon tissues was increased， while the relative fluorescence intensities of ZO-1 and occludin in colon tissues and TH in the substantia nigra were decreased （P＜0.05）. HE staining showed focal necrosis in the mucosal layer of colon tissues， disappearance of some intestinal glands， extensive inflammatory cell infiltration， and proliferation of fibrous connective tissue in the submucosa. Compared with the model group， both the Madopar group and BSHXF group showed varying degrees of improvement in the above indicators （P＜0.05）. Pathological damage in colon tissues was also alleviated， with only mild fibrous tissue proliferation and limited diffuse inflammatory cell infiltration observed in the mucosal layer. Compared with the Madopar group， rats in the BSHXF group exhibited increased average speed， central-zone distance， and latency to fall in the rotarod test. The levels of pSer129-α-syn and α-syn proteins in the substantia nigra were decreased， while VAMP2 protein expression was increased. In colon tissues， SYP protein levels and mRNA expression were elevated. The relative fluorescence intensity of ZO-1 in colon tissues and TH in substantia nigra tissues was also increased （P＜0.05）. ConclusionBSHXF may improve motor dysfunction in PD by regulating synaptic vesicle cycling， restoring intestinal barrier integrity， and improving neuronal synaptic function through modulation of synaptic vesicle-associated protein expression in the substantia nigra and colon tissues.

AIM: To compare the differences in intraocular pressure and anterior segment biometric parameters among Tibetan populations permanent residing at different altitudes in Xizang autonomous region, and to explore the impact of high-altitude environments on ocular characteristics.

METHODS:This was a retrospective cross-sectional study. Data were collected from Tibetan patients who visited the People's Hospital of Xizang Autonomous Region from September 2019 to October 2021. Participants were divided into two groups based on their permanent residence altitude: a higher altitude group(2 500-3 750 m)and a very high-altitude group(>3 750 m). The eye with better best corrected visual acuity was selected for each participant. Intraocular pressure, refractive error, and anterior segment biometric measurements \〖white-to-white corneal diameter(WTW), central corneal thickness(CCT), anterior chamber depth(ACD), lens thickness(LT), axial length(AL)\〗 were recorded and compared between the two groups.

RESULTS: A total of 43 Tibetan patients(43 eyes)were enrolled in this study, comprising 23 males and 20 females, with a mean age of 57.88±13.90 y. There were 19 patients(19 eyes)in the very high-altitude group and 24 patients(24 eyes)in the higher altitude group. The mean intraocular pressure in the very high-altitude group was 11.79±1.72 mmHg, which was significantly lower than 13.44±2.43 mmHg in the higher altitude group(P=0.019). CCT in the very high-altitude group was 482.70±23.76 μm, significantly thinner than 503.00±31.09 μm in the higher altitude group(P=0.012). AL in the very high-altitude group was 22.96±0.96 mm, significantly shorter than 23.64±1.10 mm in the higher altitude group(P=0.020). No statistically significant differences were found between the two groups in WTW, ACD, LT, or refractive error(all P>0.05).

CONCLUSION:Among the Tibetan population in Xizang autonomous region, as the altitude of residence increases, intraocular pressure significantly decreases, CCT becomes thinner and AL shortens. These morphological changes suggest possible adaptive remodelling of the eye in very high-altitude environments, and a thinner cornea may be an important factor contributing to the lower measured intraocular pressure values.

Objective To explore the sleep quality and mental fatigue level in elderly patients with cerebrovascular small disease(CSVD).Methods A total of 222 patients aged over 65 years old hospitalized due to chronic diseases in Department of Neurology of the Affiliated Jiangning Hospi-tal of Nanjing Medical University from August 2022 to June 2024 were recruited prospectively and continuously.According to the CSVD score,they were divided into a CSVD group(CSVD score≥1,148 cases)and a non-CSVD group(CSVD score=0,74 cases).All the patients were evaluated by sleep quality,fatigue and neuropsychological scale when they were fully cooperated and in good condition.Subsequently,the patients in the CSVD group were further assigned into a good sleep subgroup(117 cases)and a poor sleep subgroup(31 patients).Results The CSVD group had significantly higher total score of Pittsburgh sleep quality index(PSQI),sleep quality score,sleep disturbance score,total score of self-rating fatigue,and mental fatigue score than the non-CSVD group(P＜0.01).The sleep quality score,sleep disturbance score,and mental fatigue score were risk factors for CSVD(P＜0.05).The mental fatigue score was significantly higher in the CSVD patients with poor sleep than those with good sleep(4.13±1.15 vs 2.50±1.92,P＜0.01).Conclusion Elderly CSVD patients were more likely to have decreased sleep quality and mental fatigue,and among them,those with poor sleep quality are prone to having mental fatigue than those with good sleep.

Objective:To observe the effect of moxibustion on angiogenesis-related indicators in knee joint synovial tissue of adjuvant arthritis model rats,and to explore the mechanism of moxibustion in inhibiting vascular endothelial growth factor(VEGF)expression in synovial tissue and further limiting the activation of Rho family proteins Rac1 and Cdc42,thereby inhibiting angiogenesis during rheumatoid arthritis(RA)treatment.Methods:Forty-eight male Sprague-Dawley rats were equally divided into a normal group,a model group,a moxibustion group,and a moxibustion+VEGF agonist group according to the random principle.The complete Freund's adjuvant method was used for modeling.On the 12th day after modeling,the moxibustion group and the moxibustion+VEGF agonist group were subjected to suspended moxibustion at bilateral Zusanli(ST36),Guanyuan(CV4),and Ashi points for 20 min each time,once a day,for a total of 15 times.The moxibustion+VEGF agonist group received VEGF agonist(tirofiban hydrochloride hydrate)injection in the knee joint cavity at the same time.Hematoxylin-eosin staining was used to evaluate the pathological changes of rat synovial tissue in each group.Immunohistochemistry was used to observe the CD31 expression level in rat synovial tissue.Western blotting was used to detect the levels of VEGF,Rac1,and Cdc42 protein in rat synovial tissue,and polymerase chain reaction(PCR)was used to detect the VEGF mRNA expression.Results:Compared to the normal group,the expression levels of CD31 protein and VEGF mRNA and protein in rat synovial tissue in the model group increased significantly(P<0.01),and the expression levels of phospho-Rac1 and phospho-Cdc42 proteins also increased significantly(P<0.01).After moxibustion intervention,the expression levels of CD31 protein and VEGF mRNA and protein in the moxibustion group were significantly lower than those in the model group(P<0.01),while the differences in each indicator between the moxibustion+VEGF agonist group and the model group were not statistically significant(P>0.05).Compared to the moxibustion group,the expression levels of CD31 protein,VEGF mRNA and protein,phospho-Cdc42,and phospho-Rac1 in the moxibustion+VEGF agonist group increased significantly(P<0.01).Conclusion:Moxibustion improved synovial inflammation in RA by inhibiting angiogenesis.The mechanism may be to regulate angiogenesis-related VEGF,restrict the activation of Rac1 and Cdc42,and inhibit pseudopodia formation in vascular endothelial cells,thereby reducing angiogenesis.

Objective:To present the epidemiological characteristics of ≤28 days case fatality in both hemorrhagic stroke (HS) and ischemic stroke (IS) patients in national cardiovascular disease surveillance areas from 2015 to 2019.Methods:Data on all new patients with stroke and ≤28 days outcomes from 2015 to 2019 were from the China Registry of Cardiovascular Events, which was established in 2014, covering 100 counties (cities, districts) in 31 provinces in China. Poisson regression was used to analyze the annual trend of ≤28 days case fatality. The age-standardized case fatality was directly calculated based on all new stroke onset.Results:In total, 112 069 deaths in HS patients ≤28 days after the onset, as well as 94 373 in IS patients, were identified during the study period. In 2019, the ≤28 days case fatality rate in HS patients was 4.75 times that of IS patients (37.08% vs. 7.80%), as well as that 4.06 times in urban areas (30.13% vs. 7.43%) and 5.30 times in rural areas (42.63% vs. 8.05%), respectively. Thus, in rural areas, HS patients showed 41.49% higher ≤28 days case fatality rate than that in urban areas, as well as 8.34% higher in IS patients. Those ≤28 days case fatality in both stroke subtypes onset increased with age and reached the highest level in those aged 85 years and over. During the study period, HS and IS patients in each age group displayed significant decrease trend in ≤28 days case fatality rate (trend P<0.001). Compared with that in 2015, the age-standardized ≤28 days case-fatality in HS patients in 2019 decreased by 28.52%, which was more in urban areas (-34.27%) than that in rural areas (-23.19%). Meanwhile, IS patients experienced a 39.90% reduction in ≤28 days case fatality, which was much lower in urban areas (-31.62%) than in rural areas (-45.10%, all trend P<0.001). Conclusions:From 2015 to 2019, ≤28 days case fatality in both HS and IS patients decreased in China. Wide variations of ≤28 days case-fatality were evident in the level and trend in stroke subtype, age of patients, as well as urban and rural areas. More precise and comprehensive strategies for stroke prevention, treatment, and post-stroke management are urgently required in China.

Objective:To explore the surgical strategies and clinical efficacy of open partial nephrectomy in the treatment of renal angiomyolipoma (AML) with inferior vena cava tumor thrombus.Methods:A retrospective analysis was conducted on the clinical data of 5 patients with renal AML and inferior vena cava tumor thrombus who underwent partial nephrectomy at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to December 2022. There were 2 male and 3 female patients, with a median age of 37 years, ranged from 33 to 45 years. All patients were identified during routine physical examinations. Four patients presented with right-sided lesions, while one had a left-sided lesion. The diameter of the primary tumor within the kidney ranged from 3.0 to 7.0 cm, with a median diameter of 5.5 cm.The length of the tumor thrombus within the inferior vena cava ranged from 1.0 to 6.0 cm, with a median length of 1.5 cm. Among them, 2 patients underwent laparoscopic nephrectomy combined with extracorporeal workbench tumor resection and autologous kidney transplantation (the workbench surgery group), while 3 patients underwent open in-situ partial nephrectomy combined with removal of inferior vena cava tumor thrombus (the in-situ nephron-sparing surgery group). The surgical method of the workbench surgery group: The patients first underwent laparoscopic nephrectomy on the affected side combined with inferior vena cava tumor thrombus removal, then the incision was extended to remove the affected kidney, and table partial nephrectomy was performed. After completely removing the tumor and tumor thrombus within the affected kidney and renal vein, autologous kidney transplantation was performed in the iliac fossa. The surgical method of the in-situ kidney preservation surgery group: The affected kidney, renal artery and vein on the affected side, inferior vena cava, and contralateral renal vein were dissected and exposed. The distal end of the inferior vena cava, the contralateral renal vein, the proximal end of the inferior vena cava, and the renal artery on the affected side were blocked respectively. The venous wall was opened in the middle of the renal vein, and the tumor thrombus was gradually pulled out. According to the pre-marked tumor boundary, the tumor within the kidney was gradually removed by alternate blunt and sharp dissection combined with suction, and the wound surface was sutured layer by layer. The perioperative conditions, complications, and follow-up results of the patients were analyzed.Results:All 5 surgeries were successfully completed, with a median operation time of 100 to 450 minutes and a median operation time of 200 minutes. The intraoperative bleeding volume was 100 to 600 ml, with the median of 150 ml. In the in-situ nephron-sparing surgery group, the renal artery occlusion time was 28 to 41 minutes, and the median occlusion time was 34 minutes. All patients were discharged safely after surgery, and there were no serious perioperative complications. The postoperative pathology of all 5 patients was renal angiomyolipoma, without any epithelioid components. The patients were followed up for 12 to 90 months, with a median follow-up duration of 24 months. None of the 5 patients had tumor recurrence or metastasis, and no patient developed chronic kidney dysfunction during follow-ups.Conclusions:Renal AML with venous tumor thrombus is a challenging clinical problem. In situ open partial nephrectomy or the combined approach through the workbench and autologous kidney transplantation can effectively remove the tumor thrombus and maximize the protection of renal function. For cases of ① multiple or complex renal AML; ② complex vascular system structure within the renal sinus requiring precise anatomy; ③ renal AML with a previous history of hemorrhage, complex adhesions around, and difficult dissociation, table partial nephrectomy combined with inferior vena cava tumor thrombus removal and autologous kidney transplantation can be selected. For cases where the expected surgical operation is simple, in situ open partial nephrectomy can significantly shorten the operation time and reduce surgical trauma.

Objective:To explore the medication thinking and compatibility rules of TCM for the treatment of diabetic nephropathy (DN).Methods:Relevant journal literature of TCM for the treatment of DN was retrieved from CNKI, Wanfang Data, VIP, and CBM from January 1, 2000 to December 31, 2023, and a database was established through Excel 2016. Python 3.10 and the ancient and modern medical record cloud platform 2.3.5 were used to conduct Latent Dirichlet Allocation (LDA) topic modeling and association rule analysis to explore the thinking and compatibility rules of TCM prescriptions in the literature.Results:A total of 474 articles were included in the study, including 474 prescriptions, involving 260 kinds of Chinese materia medica, of which 40 kinds of Chinese materia medica with a frequency of ≥ 30, mainly Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Dioscoreae Rhizoma, Poria, and Corni Fructus, etc. The LDA topic model identified three groups of prescriptions, including four classic prescriptions: Liuwei Dihuang Pills, Taohong Siwu Decoction, Erzhi Pills, and Wuling Powder. The commonly used drug combinations extracted by association rules were: Rhizoma Alismatis - Poria, Cortex Moutan Radicis-Fructus Corni and Cortex Moutan Radicis - Rhizoma Dioscoreae.Conclusions:The main therapeutic principle of TCM in treating DN is to nourish the yin and tonify the kidney, supplemented by drugs that promoting blood circulation for removing blood stasis as well as promoting urination and draining dampness. In clinical application, modern doctors tend to use classic prescriptions such as Liuwei Dihuang Pills, Erzhi Pills, Taohong Siwu Decoction, and Wuling Powder as the basis, and modify them according to the specific conditions of patients. The LDA topic model can extract valuable prescription information from a large number of modern TCM literature, providing new perspectives and ideas for the study of clinical medication rules in TCM.

Objective This study aims to explore the efficacy and complication rates of the transcranial approach(TCA)and extended endoscopic endonasal approach(EEEA)for the treatment of craniopharyngiomas based on the QST classification,providing a scientific reference for clinical decision-making on surgical approach.Methods A total of 151 patients who underwent craniopharyngioma surgery at our center from January 2018 to December 2023 were enrolled.The patients were categorized into Q-CP(suprasellar type),S-CP(infundibular type),and T-CP(tuberal type)according to the QST classification.Systematic collection and analysis were performed on the outcomes of TCA and EEEA treatments,respectively.The differences in effectiveness between the two approaches were evaluated based on the QST classification.Results The improvement rate of visual symptoms was overall higher in the EEEA group than in the TCA group(59.1%vs.36.5%,P=0.006),and the visual deterioration rate was lower(3.0%vs.14.1%,P=0.006).However,the incidence of cerebrospinal fluid leakage was higher in the EEEA group(15.2%vs.3.5%,χ2=4.986,P=0.026).The incidence of postoperative seizures(8.2%vs.0,P=0.019),brain contusions(10.6%vs.0,P=0.005),and subdural hematoma(9.4%vs.0%,P=0.01)was higher in the TCA group.For patients with Q-CP type,the EEEA group had a higher rate of total tumor resection(92.9%vs.65.2%,P=0.025)and a lower recurrence rate(3.6%vs.21.7%,P=0.047),with shorter hospital stays and lower postoperative costs.The TCA group had higher intraoperative blood loss in this type(300 mL vs.200 mL,Z=-2.261,P=0.024).For S-CP type patients,the EEEA group showed a higher rate of total tumor resection(91.3%vs.74.2%)and a lower recurrence rate(0 vs.12.9%,P=0.031),with lower postoperative hospital costs.In T-CP type,due to the deeper location,EEEA showed limitations in protecting hypothalamic function and the TCA group had a better postoperative hypothalamic function score(P=0.035).Conclusion Based on QST classification,EEEA has advantages in Q-CP and S-CP types and is recommended as the preferred surgical procedure;In the T-CP type,TCA surgery is more helpful in protecting hypothalamic function.

BACKGROUND:Titanium surface micro-nano structure modification is a hot research field in titanium implant surface treatment.The diabetic hyperglycemia environment will affect the stable bonding between titanium implant and bone tissue,so it is necessary to explore the surface micro-nano structure modification to improve the osteogenic activity of titanium implant in high glucose environment.OBJECTIVE:To investigate the effect of gold nanoparticle@mesoporous silica nanoparticles(AuNPs@MSNs)coating on osteogenic activity of osteoblasts under high glucose in vitro.METHODS:Gold nanoparticle suspension and mesoporous silica were prepared respectively,and the two were mixed in deionized water in a certain proportion to prepare gold nanoparticle@mesoporous silica suspension.Titanium sheets were taken and divided into three groups for treatment:the smooth group was treated with water sandpaper;the nanotube group was treated with water sandpaper and then anodized to prepare titanium dioxide nanotube coating,and the experimental group prepared titanium dioxide nanotube coating and then immersed in gold nanoparticle@mesoporous silica suspension to prepare gold nanoparticle@mesoporous silica nanoparticles coating.The microscopic morphology and hydrophilicity of the surface of the three groups of titanium sheets were characterized.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets.Cell proliferation was detected by cell live/dead fluorescence staining and CCK-8 assay.Cell adhesion was detected by DAPI/phalloidin staining.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets,and high-glucose osteogenic induction medium was added for culture.Osteogenic differentiation was detected by alkaline phosphatase and Alizarin Red S staining.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the titanium sheet in the smooth group was uniform and flat.The titanium dioxide nanotube arrays in the nanotube group were closely arranged on the surface,and the titanium sheet in the experimental group was loaded with gold nanoparticle@mesoporous silica on the surface and inside of the titanium dioxide nanotubes.The hydrophilicity of the titanium sheets in the nanotube group and the experimental group was better than that in the smooth group.(2)The results of cell live/dead fluorescence staining exhibited that the cell viability on the surface of the three groups of titanium sheets was higher than 90%.The results of CCK-8 assay show that the cell proliferation rate in the experimental group was higher than that in the smooth group and the nanotube group.The results of DAPI/phalloidin staining showed that the titanium dioxide nanotube coating and the gold nanoparticle@mesoporous silica nanoparticles coating were more conducive to cell adhesion.(3)The results of alkaline phosphatase and Alizarin Red S staining showed that the alkaline phosphatase activity and extracellular matrix mineralization of the cells on the titanium sheet surface in the experimental group were higher than those in the smooth group and the nanotube group.(4)The results show that the gold nanoparticle@mesoporous silica nanoparticles coating can enhance the biological activity of the titanium surface and promote osteogenic differentiation in a high glucose environment.