The blood-brain barrier in humans significantly restricts the effective delivery of drugs into the brain,resulting in poor therapeutic efficacy and difficulty in brain disease management.In recent years,innovative strategies and novel preparations have been studied and developed in order to circumvent the blood-brain barrier,achieve efficient drug entry into the brain,minimize the incidence of peripheral adverse effects,and bring significant therapeutic outcomes to patients.This review summarizes some key development strategies for treating encephalopathy,to provide some insights for the development of the next generation of drugs.

[Objective]To explore the regulatory mechanism of hypoxia exposure on carbon metabolism pathway in spleen of mice.[Methods]C57BL/6 mice were raised at altitudes of 400 m and 4 200 m,with 5 mice in each group.After 30 days,spleen tissues were aseptically removed for analysis of differentially expressed genes,proteins,and metabolites using transcriptome sequencing,proteomics,and non-targeted metabolomics.GO and KEGG enrichment analysis were conducted to explore key pathways.The key genes and protein in the pathway were validated by RT-qPCR and Western blot.[Results]Transcriptome sequencing revealed a significant difference in the expression of 4 213 genes in hypoxic exposure,of which 1 947 were up-regulated and 2 266 were down-regulated.The analysis of differentially expressed proteins showed that 166 proteins were up-regulated and 39 proteins were down-regulated.The results of non-targeted metabolomics showed that 133 different metabolites were screened under high altitude hypoxia condition,of which 95 were up-regulated and 38 were down-regulated.KEGG enrichment analysis showed that differentially expressed genes,differentially expressed proteins and differentially expressed metabolites were enriched into the carbon metabolic pathway.Therefore,the key genes and proteins in the carbon metabolic pathway were verified.The mRNA and protein expressions of PGAM2、ENO3、PRPS2、PGLS、RPE、IDH3A、SUCLA2 and MDH2 were significantly down-regulated in the carbon metabolism pathway.[Conclusion]Low oxygen environment at high altitude weakens glycolysis,tricarboxylic acid cycle and pentose phosphate pathway by inhibiting the carbon metabolism pathway of the body,resulting in oxidative stress and energy metabolism imbalance.

Isolated vertigo due to vascular mechanisms manifests as vertigo, dizziness or imbalance only. Due to the lack of focal neurological symptoms or signs, it is often misdiagnosed as peripheral vestibular disease, resulting in serious adverse consequences. This article reviews the lesion location, cerebrovascular basis, clinical evaluation, and imaging examination of isolated vertigo caused by vascular mechanisms.

Objective To investigate the role and mechanism of exosomes derived from mesenchymal stem cells in hyperbaric oxygen caused pulmonary oxygen toxicity.Methods Mice were divided into the control group that was exposed to normal air,and hyperbaric oxygen exposure groups treated with phosphate buffer saline(PBS)or exosomes,respectively.PBS and exosome treatment were given one day prior to exposure.Mice were subjected to 0.23 MPa pure oxygen for 8 hours.The lung wet-dry ratio,inflammation,exudation and pathological injury were analyzed,while cell death and antioxidant related molecules were detected.Results Pretreatment with exosome significantly attenuated lung injury caused by hyperbaric oxygen exposure by decreasing the lung wet-dry ratio,inflammation,and cell apoptosis.Conclusion Prophylactic administration of exosomes derived from mesenchymal stem cells can alleviate hyperbaric oxygen induced pulmonary oxygen poisoning by attenuating cell death and inflammation.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective:Exploring the clinical effects of silicone silver ion foam dressing in managing scalp donor site wounds in burn patients.Methods:A retrospective analysis was conducted on the clinical data of burn patients admitted to the 940th Hospital of Joint Logistics Support Force of PLA from January 2020 to January 2023. Patients underwent intraoperative harvesting of split-thickness skin grafting to repair deep burn wounds, with the denuded scalp area covered by either silicone silver ion foam dressing (Group A) or petrolatum gauze (Group B). Comparison of the following 5 parameters between the two groups: (1) Postoperative wound healing time. (2) Initial dressing change pain score was assessed using the numeric rating scale (NRS). 0 points indicated no pain, 1-3 points indicated mild pain, 4-6 points indicated moderate pain, and 7-10 points indicated severe pain. (3) Number of dressing changes. (4) Secondary trauma score, with a total score ranging from 1 to 3, where a higher score indicates more severe trauma. (5) Proportion of wounds healed to grade A (number of grade A healed cases/total number of cases in each group×100%). Depending on the data type, between-group comparisons were performed using t-test, Wilcoxon rank-sum test, or chi-square test. P<0.05 was considered a statistically significant difference. Results:A total of 60 patients, with 30 in each Group A and Group B, were included in the study. Group A was comprised of 18 males and 12 females, with an average age of (29.4±16.6) years. The burn area was (21.43±5.66)% of the total body surface area (TBSA), and the area of skin taken from the scalp was (1.80±0.61)% of TBSA. Group B was comprised of 20 males and 10 females, with an average age of (30.2±16.2) years. The burn area was (21.37±5.67)% of TBSA, and the area of skin taken from the scalp was (1.78±0.63)% of TBSA. No statistically significant differences were observed in gender distribution, age, burn area, and scalp area between the two groups( P>0.05). The wound healing time in the denuded scalp area was shorter in Group A than in Group B [(5.97±0.41) days vs. (6.93±0.58) days, t=-7.40, P<0.001]. The initial NRS pain score during dressing change was lower in Group A than in Group B [3.0 (2.0, 4.0) points vs. 5.5 (4.0, 6.0) points, Z=-4.82, P<0.001]. Group A had fewer frequency of dressing changes compared to Group B [2 (2, 2) vs. 4 (3, 5), Z=-6.64, P<0.001]. The secondary injury score was lower in Group A than in Group B [1 (1, 1) points vs. 3 (3, 3) points, Z=-7.08, P<0.001]. The proportion of grade A healing was 96.7% (29/30) in Group A and 90.0% (27/30) in Group B, with no statistically significant difference between the two groups ( χ2=0.27, P=0.605). Conclusion:The application of silicone silver ion foam dressing to cover the denuded scalp area of burn patients significantly improves therapeutic efficacy compared to petrolatum gauze. It can shorten wound healing time, reduce the frequency of dressing changes, alleviate pain, minimize the occurrence of secondary injuries, and enhance patient comfort.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective To explore the value of shear wave elastography(SWE)in the early assessment of hepatic and renal fibrosis in patients with metabolic associated fatty liver disease(MAFLD).Methods A total of 52 MAFLD patients admitted to the Second Affiliated Hospital of Wenzhou Medical University from July 2023 to May 2024 were selected as MAFLD group,and 40 non-MAFLD patients treated during the same period were served as control group.General information,laboratory data and ultrasound data were collected and compared between two groups.The differences as well as the correlation of the indicators between two groups were compared.The value of SWE in hepatic fibrosis and renal fibrosis in MAFLD patients was assessed.Results Liver function indicators,uric acid and aspartate aminotransferase-to-platelet ratio index(APRI)in MAFLD group were higher than those in control group(P＜0.01);There were no statistically significant differences between two groups in fibrosis 4 index,estimated glomerular filtration rate,serum creatinine and blood urea nitrogen(P＞0.05).The brightness of the liver,liver-kidney ratio,and liver elasticity value were higher in MAFLD group than those in control group(P＜0.05);There was no significant difference in the elasticity value of the right renal cortex between two groups(P＞0.05).Liver elasticity values was positively correlated with alanine aminotransferase(ALT);The liver-kidney ratio was positively correlated with body mass index(BMI),ALT,aspartate aminotransferase,alkaline phosphatase,y-glutamyl transferase and APRI.No significant correlation was found between the right renal cortex elasticity and BMI,estimated glomerular filtration rate,serum creatinine,blood urea nitrogen,or serum uric acid.Conclusion SWE helps in early identification of liver hardness in the MAFLD patients.But the application of SWE in early renal fibrosis in the MAFLD patients needs further evaluation.

Objective:Exploring the clinical effects of silicone silver ion foam dressing in managing scalp donor site wounds in burn patients.Methods:A retrospective analysis was conducted on the clinical data of burn patients admitted to the 940th Hospital of Joint Logistics Support Force of PLA from January 2020 to January 2023. Patients underwent intraoperative harvesting of split-thickness skin grafting to repair deep burn wounds, with the denuded scalp area covered by either silicone silver ion foam dressing (Group A) or petrolatum gauze (Group B). Comparison of the following 5 parameters between the two groups: (1) Postoperative wound healing time. (2) Initial dressing change pain score was assessed using the numeric rating scale (NRS). 0 points indicated no pain, 1-3 points indicated mild pain, 4-6 points indicated moderate pain, and 7-10 points indicated severe pain. (3) Number of dressing changes. (4) Secondary trauma score, with a total score ranging from 1 to 3, where a higher score indicates more severe trauma. (5) Proportion of wounds healed to grade A (number of grade A healed cases/total number of cases in each group×100%). Depending on the data type, between-group comparisons were performed using t-test, Wilcoxon rank-sum test, or chi-square test. P<0.05 was considered a statistically significant difference. Results:A total of 60 patients, with 30 in each Group A and Group B, were included in the study. Group A was comprised of 18 males and 12 females, with an average age of (29.4±16.6) years. The burn area was (21.43±5.66)% of the total body surface area (TBSA), and the area of skin taken from the scalp was (1.80±0.61)% of TBSA. Group B was comprised of 20 males and 10 females, with an average age of (30.2±16.2) years. The burn area was (21.37±5.67)% of TBSA, and the area of skin taken from the scalp was (1.78±0.63)% of TBSA. No statistically significant differences were observed in gender distribution, age, burn area, and scalp area between the two groups( P>0.05). The wound healing time in the denuded scalp area was shorter in Group A than in Group B [(5.97±0.41) days vs. (6.93±0.58) days, t=-7.40, P<0.001]. The initial NRS pain score during dressing change was lower in Group A than in Group B [3.0 (2.0, 4.0) points vs. 5.5 (4.0, 6.0) points, Z=-4.82, P<0.001]. Group A had fewer frequency of dressing changes compared to Group B [2 (2, 2) vs. 4 (3, 5), Z=-6.64, P<0.001]. The secondary injury score was lower in Group A than in Group B [1 (1, 1) points vs. 3 (3, 3) points, Z=-7.08, P<0.001]. The proportion of grade A healing was 96.7% (29/30) in Group A and 90.0% (27/30) in Group B, with no statistically significant difference between the two groups ( χ2=0.27, P=0.605). Conclusion:The application of silicone silver ion foam dressing to cover the denuded scalp area of burn patients significantly improves therapeutic efficacy compared to petrolatum gauze. It can shorten wound healing time, reduce the frequency of dressing changes, alleviate pain, minimize the occurrence of secondary injuries, and enhance patient comfort.

Ferroptosis, a new form of programmed cell death marked by iron-dependent phospholipid peroxidation, is regulated by complex cellular metabolic pathways, including iron metabolism, lipid metabolism, and oxidation-reduction system, is associated with many organ injuries and degeneration, and has great potential in the treatment of ischemic diseases and lipid peroxide-related degenerative diseases. Myocardial ischemia reperfusion injury (MIRI) is the most common cause of death in patients with acute myocardial infarction after revascularization therapy. Recent studies have shown that ferroptosis is intimately related to the pathological process of MIRI. Ferroptosis is associated with MIRI through oxidative stress, iron metabolism, lipid metabolism, endoplasmic reticulum stress and inflammatory response. Intervention of ferroptosis during reperfusion can effectively improve cardiac function and reduce myocardial infarct size. In this paper, the research progress was explored between ferroptosis and MIRI, and the specific role of ferroptosis in MIRI was discussed.