Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with al-terations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,trans-mission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assess-ment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

ObjectiveTo observe the effect of Shenghuitang on serum levels of neurotransmitters in the mouse model of Alzheimer's disease （AD） and explore the mechanism of Shenghuitang in mitigating the cognitive impairment and circadian rhythm disturbance of AD. MethodTwenty-seven APP/PS1 dementia mice were randomly assigned into a model group， a donepezil （0.92×10^-4 g·kg^-1·d^-1） group， and a Shenghuitang （13.5 g·kg^-1·d^-1） group. Another nine wild-type C57BL/6JNju mice was set as the control group. The mice were administrated with corresponding drugs by gavage and the control and model groups were given the same volume of pure water. Every group was continuously treated for 4 weeks. The cognitive function and circadian rhythm of mice were evaluated by Morris water maze test and open field test. The liquid chromatography-tandem mass spectrometry （LC-MS/MS） was employed to determine the expression levels of acetylcholine （ACh）， choline acetyltransferase （ChAT）， norepinephrine （NE）， epinephrine （E）， glutamate （Glu）， 5-hydroxyindoleacetic acid （5-HIAA）， and dopamine （DA） in the serum. ResultCompared with the control group， the modeling increased the escape latency， swimming distance， time of first arrival on the platform， activity time of light environment， activity time of dark environment， and total activity time （P<0.01）， while it decreased the number of crossing the platform and the swimming time in the target quadrant （P<0.01）. Compared with the model group， donepezil and Shenghuitang decreased the escape latency， swimming distance， time of first arrival on the platform， activity time of light environment， activity time of dark environment and total activity time （P<0.05， P<0.01）， while they increased the number of crossing the platform and the swimming time in the target quadrant （P<0.05， P<0.01）. Compared with the control group， the modeling down-regulated the expression levels of ACh and ChAT in the serum （P<0.01）. Compared with the model group， donepezil and Shenghuitang up-regulated the expression levels of ACh and ChAT in the serum （P<0.05， P<0.01）. Compared with the control group， the modeling up-regulated the expression level of Glu in the serum （P<0.01） and down-regulated the expression levels of NE， 5-HIAA， and DA （P<0.01）. Compared with the model group， Shenghuitang down-regulated the expression level of Glu （P<0.05） and up-regulated the expression levels of NE， 5-HIAA， and DA （P<0.05， P<0.01）. The expression levels of NE， Glu， 5-HIAA， and DA in the donepezil group did not change significantly compared with those in the model group. The expression level of E showed no significant difference among different groups. ConclusionShenghuitang may ameliorate the cognitive impairment and circadian rhythm disturbance of AD mice by regulating the levels of neurotransmitters in the serum.

To analyze the clinical characteristics and genetic data of a child with type Ⅱ Bruce syndrome (type Ⅱ BS) admitted to the Department of Orthopedics, Shanxi Children′s Hospital at May 2020.A 3-day-old boy was admitted due to the pain and swelling of the right lower limb 3 days after birth.Due to the patient had multiple fractures, callus formation after clavicle and rib fracture, greendstick fracture of the humerus, right femur fracture, left tibia and fibula fracture, congenital clubfoot, and congenital contracture of wrist, elbow, hip and knee joint, and therefore, chromosome diseases were considered.Gene sequencing data showed gene mutation in PLOD2 with compound heterozygosity deletion of the child (proband), and mutation and heterozygosity deletion came from their parents, respectively.The patient was diagnosed as type Ⅱ BS.This case report alarms clinicians to identify a missense mutation of PLOD2 and loss of heterozygosity, so as to reduce the misdiagnosis rate and achieve early diagnosis and treatment.

Objective:To investigate the clinical effect of minimally invasive treatment of supracondylar fracture of humerus with nerve injury and the need for surgical exploration of nerve.Methods:From August 2017 to September 2020, 34 cases of children with supracondylar fracture of humerus with nerve injury in the Department of orthopedics of Shanxi Children′s Hospital were selected for retrospective analysis.Closed reduction, Kirschner wire fixation and small incision surgery were used to explore the injured nerve.The follow-up period ranged from 6 months to 3 years, with a follow-up time of (2.15±0.49) years.The elbow function, radial nerve, median nerve and ulnar nerve function were evaluated according to the trial standard of upper limb peripheral nerve function evaluation of Hand Surgery Society of Chinese Medical Association.Results:The elbow function of children in this group: excellent 31 cases, good 2 cases, fair 1 cases, poor 0 cases, excellent 33 cases.Three patients failed to take early functional rehabilitation exercise.Two patients recovered after 2.5 months of treatment by professional orthopedic rehabilitation therapists and physical therapy.One of them did not cooperate with functional rehabilitation training.After 3.5 months of treatment by orthopedic rehabilitation therapists, elbow and finger functions were not affected.Two weeks after nerve injury: radial nerve function evaluation: excellent in 15 cases, good in 3 cases, fair in 4 cases, poor in 0 cases, excellent in 18 cases.Median nerve function evaluation: excellent in 5 cases, good in 2 cases, fair in 6 cases, poor in 0 cases, excellent in 7 cases.Ulnar nerve function evaluation: excellent 5 cases, good 0 cases, fair 1 cases, poor 0 cases, excellent 5 cases.At 3 months after injury, the excellent and good rate of radial nerve, median nerve and ulnar nerve was 100%.Conclusion:The supracondylar fracture of humerus with nerve injury is treated by minimally invasive surgery, and the nerve exploration is still a few.The recovery of nerve injury after surgery is smooth, and the clinical effect is good.

Objective:To study the changes in hemorheology in cirrhotic patients with portal hypertension before and after splenectomy.Methods:The data on cirrhotic patients with portal hypertension and hypersplenism who underwent splenectomy from January 2018 to May 2019 in the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine was analyzed. The hemorheology indexes were monitored during the perioperative period, and portal vein thrombosis was monitored by Color Doppler ultrasound.Results:A total of 30 patients were included, including 18 males and 12 females; aged 12.0-62.0 (31.7±14.0) years. One week after splenectomy, portal vein thrombosis was found in all the patients and it disappeared after heparin treatment. The leukocyte and bilirubin levels significantly improved after splenectomy ( P<0.05). The viscosity of high, medium and low cut blood, platelet and D-dimer significantly increased ( P<0.05). Conclusions:After splenectomy, blood viscosity and platelets of cirrhotic patients with portal hypertension and hypersplenism increased, and portal vein thrombosis formed easily.

Objective:To analyze the epidemiological and etiological characteristics of a dengue fever outbreak in Hunan province in 2018.Methods:Real-time PCR assay was performed for the laboratory diagnosis of 8 suspected dengue fever cases. Etiological surveillance was performed in 186 suspected dengue fever cases and fever cases who had close contacts with dengue fever patients. C6/36 cells was used for the virus isolation from acute phase serum. By sequencing the full length of E genes of 15 dengue virus strains, phylogenetic analysis was performed based on the sequences obtained, including reference sequences from the NCBI GenBank database, the serotypes and gene subtypes of the virus were analyzed to trace the possible source of transmission. An emergency monitoring of vector density and a retrospective survey of sero-epidemiology in healthy population were conducted in the epidemic area.Results:In the serum samples of 8 suspected patients, 6 were dengue virus RNA positive, and 4 were NS1 antigen positive. In 186 suspected patients, 96 were dengue virus nucleic acid, NS1 antigen or antibody positive in etiological test. A total of 64 dengue virus strains were isolated. The phylogenetic analysis showed that all the dengue virus strains belonged to type 2, which might be from Guangdong or Zhejiang provinces. The Bretub index was up to 65, indicating an extremely high risk of transmission. The positive rate of the dengue virus IgG antibody was 0.53%(2/377) in retrospective survey of 377 healthy people.Conclusion:The field epidemiologic and the molecular genetics analyses showed the outbreak of dengue fever in Hunan in 2018 was caused by imported cases and dengue virus 2.

Objective To explore the clinical features,diagnoses,differential diagnoses and treatments of superior cerebellar artery aneurysms.Methods The clinical data of 16 patients with superior cerebellar artery aneurysms,admitted to our hospital from January 2013 to March 2018,were retrospectively collected.Their clinical manifestations,imaging features,surgical effects and related problems in the process of diagnoses and treatments were analyzed.Results Among the 16 patients,11 were caused by aneurysm rupture;8 had subarachnoid hemorrhage alone,and three had subarachnoid hemorrhage accompanied by ventricular hemorrhage;CT and CTA confirmed that 8 were superior cerebellar artery aneurysms,two were posterior cerebral artery aneurysms,and one was with unclear diagnosis.In the other 5 patients,three had eyelid ptosis and two had abducent nerve palsy;CT,CTA or MR imaging showed that two were considered as ventral brainstem occupying lesions,and three did not have clear diagnosis.Finally,all patients were diagnosed as having superior cerebellar artery aneurysms by three-dimensional DSA.Five patients were treated with interventional embolization first,and one was treated with surgical clipping because of vertebral artery stenosis and difficulty of catheter access;two patients were transferred to our department for surgical clipping due to aneurysm rupture after embolization treatment in other hospitals;and 9 patients were treated by surgical clipping directly.After treatments,one patient was in bed for a long time due to cerebellar infarction and systemic complications,and the other 15 patients recovered well;two of them underwent ventricular peritoneal shunt due to hydrocephalus.Conclusions Superior cerebellar artery aneurysm has onset of subarachnoid hemorrhage mostly,and oculomotor and abductor nerve paralysis,and space occupying manifestation around the brainstem sometimes.For patients with suspicious posterior circulation aneurysms whose diagnosis or location are unclear,three-dimensional DSA examination should be performed early to confirm the diagnosis.Treatment should be taken as soon as possible once the superior cerebellar artery aneurysm is defined.Interventional embolization may be the first choice,but it is necessary to master the methods of surgical clipping in order to treat the disease timely.