Objective To explore the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus.Methods A total of 100 patients with hypertension complicated with type 2 diabetes mellitus who were treated in Nanchang Third Hospital from October 2022 to August 2023 were selected as the research subjects.They were divided into the control group and the study group by the random number table method,with 50 cases in each group.Both groups of patients received conventional antihypertensive,hypoglycemic,and antiplatelet therapy.The control group took 20 mg of atorvastatin calcium tablets orally,once a night.On the basis of the control group,the study group was additionally given 150 mg of evolocumab injection(a PCSK9 inhibitor)by subcutaneous injection,once every two weeks.Both groups of patients were followed up for 24 weeks.The levels of blood lipids,blood glucose,inflammatory cytokines,carotid intima-media thickness(IMT),atherosclerotic plaque score and adverse reactions of the patients in the two groups before and after treatment were detected and compared.Results The levels of TC,TG and LDL-C in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜0.05).The levels of IL-1,IL-6,TNF-α,hs-CRP,as well as the ca-rotid IMT and atherosclerotic plaque score in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜O.05).During the treatment period,there was no significant difference in the occurrence of adverse reac-tions between the two groups(P＞0.05).Conclusion The combination of PCSK9 inhibitor and atorvastatin can effectively regulate the blood lipid levels of patients with hypertension complicated and type 2 diabetes mellitus,alleviate the inflammatory response,and improve the degree of carotid atherosclerosis in these pa-tients.

OBJECTIVE: To investigate the short-term effectiveness of uni-portal non-coaxial spinal endoscopic surgery (UNSES) via crossing midline approach (CMA) in the treatment of free lumbar disc herniation (FLDH). METHODS: Between March 2024 and June 2024, 16 patients with FLDH were admitted and treated with UNSES via CMA. There were 9 males and 7 females with an average age of 55.1 years (range, 47-62 years). The disease duration was 8-30 months (mean, 15.6 months). The pathological segments was L _{3, 4} in 4 cases, L _{4, 5} in 5 cases, and L ₅, S ₁ in 7 cases. The preoperative pain visual analogue scale (VAS) score was 6.9±0.9 and the Oswestry disability index (ODI) was 57.22%±4.16%. The operation time, intraoperative bleeding volume, postoperative hospital stay, and incidence of complications were recorded. The spinal pain and functional status were evaluated by VAS score and ODI, and effectiveness was evaluated according to the modified MacNab criteria. CT and MRI were used to evaluate the effect of nerve decompression. RESULTS: All 16 patients underwent operation successfully without any complications. The operation time was 63-81 minutes (mean, 71.0 minutes). The intraoperative bleeding volume was 47.3-59.0 mL (mean, 55.0 mL). The length of hospital stay after operation was 3-4 days (mean, 3.5 days). All patients were followed up 1-3 months, with 15 cases followed up for 2 months and 14 cases for 3 months. The VAS score and ODI gradually decreased over time after operation, and there were significant differences between different time points ( P<0.05). At 3 months after operation, the effectiveness was rated as excellent in 12 cases and good in 2 cases according to the modified MacNab criteria, with an excellent and good rate of 100%. CT and MRI during follow-up showed a significant increase in the diameter and cross-sectional area of the spinal canal, indicating effective decompression of the canal. CONCLUSION When using UNSES to treat FLDH, choosing CMA for nerve decompression has the advantages of wide decompression range, large operating space, and freedom of operation. It can maximize the preservation of the articular process, avoid fracture and breakage of the isthmus, clearly display the exiting and traversing nerve root, and achieve good short-term effectiveness.
Humans ; Male ; Intervertebral Disc Displacement/diagnostic imaging* ; Middle Aged ; Female ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Treatment Outcome ; Operative Time ; Pain Measurement ; Length of Stay

Objective To screen and analyze the differentially expressed genes(DEGs)in basal cell carcinoma(BCC)of the eyelid using RNA sequencing technology.Methods Six patients who underwent extended resection and primary eyelid reconstruction for BCC of the eyelid in Hebei Eye Hospital from July to November 2021 were selected.Part of the excised cancer tissues and the adjacent normal tissues trimmed during the repair of the defect were sampled for the study.The library construction for sequencing was performed using RNA sequencing technology.The threshold for DEGs was set using the DESeq2 software:P＜0.05 and|log2(foldchange)|＞1,to identify DEGs.Gene Ontology(GO)and Kyo-to Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using the clusterProfiler software,and the biological significance of these DEGs was further analyzed.Results DESeq2 software was used to analyze the differential expression between cancer tissues and adjacent tissues,and 1 317 DEGs were screened out.In the cancer tis-sues of the 6 patients,906 DEGs were up-regulated,and 411 DEGs were down-regulated.GO enrichment analysis showed that the top 30 up-regulated DEGs were mainly concentrated in humoral immune response,immunoglobulin complex,B cell receptor signaling pathway,extracellular matrix,antigen binding,and receptor modulator activity,and the top 10 down-regulated genes were mainly related to epidermal development in biological process,cell composition,and molecular func-tion.KEGG pathway analysis revealed that DEGs were mainly enriched in the melanogenesis signaling pathway,WNT sig-naling pathway,and immune-related signaling pathway,and there were 8 related gene pathways.According to the signifi-cance of gene up-regulation,the core genes identified finally were FZD2,PTCH1,WNT7B,TCF3,MMP-9,and TEAD2.Conclusion The occurrence of BCC is closely related to the interaction and synergy of various pathways.Among the highly expressed genes,the up-regulation of FZD2,PTCH1,WNT7B,TCF3,MMP-9,and TEAD2 expression in the tissues of patients with BCC of the eyelid is the most significant,which is closely related to the occurrence and development of BCC of the eyelid.

Objective:To explore the long term efficacy of absorbable sutures coated with silver nanoparticles on the suture track of skin incisions in mice.Methods:This study was an experimental research. Eighteen half male and half female BALB/c mice aged 10-12 weeks were divided into normal Vicryl suture group, antibiotic Vicryl suture group, and silver nanoparticle Vicryl suture group according to the random number table, with 6 mice in each group, half male and half female. After the skin incisions were created on the back of all mice, the skin incisions of mice in normal Vicryl suture group, antibiotic Vicryl suture group, and silver nanoparticle Vicryl suture group were performed with continuous intradermal suture by absorbable Vicryl sutures, absorbable Vicryl sutures coated with triclosan antimicrobial, and absorbable Vicryl sutures coated with silver nanoparticles, respectively. On the 25 th day after surgery, the skin tissue in the suture track of incisions was collected, immunohistochemical staining was used to detect the percentages of F4/80, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) positive areas in the suture track of incisions of mice, the TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the percentage of TUNEL staining positive area in the suture track of incisions of mice, Masson staining was used to observe the collagen fiber formation in the suture track of incisions of mice, and immunohistochemical staining was used to detect the percentage of tissue cathepsin K positive area in the suture track of incisions of mice. The number of the above experimental samples was 6. Results:On the 25 th day after surgery, the percentages of F4/80, IL-6, and TNF-α positive areas in the suture track of incisions of mice in silver nanoparticle Vicryl suture group ((19.2±1.6)%, (20.2±1.7)%, and (16.0±1.6)%) were significantly lower than those in normal Vicryl suture group ((100±6.4)%, (100±7.6)%, and (100±9.6)%) and antibiotic Vicryl suture group ((47.2±3.2)%, (53.8±5.0)%, and 43.2%, P<0.05). The percentages of F4/80, IL-6, and TNF-α positive areas in the suture track of incisions of mice in antibiotic Vicryl suture group were significantly lower than those in normal Vicryl suture group ( P<0.05). On the 25 th day after surgery, the percentage of TUNEL staining positive area in the suture track of incisions of mice in silver nanoparticle Vicryl suture group was significantly lower than those in normal Vicryl suture group and antibiotic Vicryl suture group (with both P values <0.05). The percentage of TUNEL staining positive area in the suture track of incisions of mice in antibiotic Vicryl suture group was significantly higher than that in normal Vicryl suture group ( P<0.05). On the 25 th day after surgery, the collagen fiber deposition was not obvious in the suture track of incisions of mice in normal Vicryl suture group, no obvious collagen fiber formation was observed in the suture track of incisions of mice in antibiotic Vicryl suture group, while the collagen fibers were mostly densely arranged and well-ordered in the suture track of incisions of mice in silver nanoparticle Vicryl suture group. On the 25 th day after surgery, the percentage of tissue cathepsin K positive area in the suture track of incisions of mice in silver nanoparticle Vicryl suture group was significantly lower than those in normal Vicryl suture group and antibiotic Vicryl suture group (with P values both <0.05), the percentage of tissue cathepsin K positive area in the suture track of incisions of mice in antibiotic Vicryl suture group was significantly lower than that in normal Vicryl suture group ( P<0.05). Conclusions:In the suture track of incisions of mice, silver nanoparticle Vicryl sutures exhibit superior long-term anti-inflammatory effects compared with absorbable Vicryl sutures coated with triclosan antimicrobial and normal absorbable Vicryl sutures. Additionally, cell apoptosis is reduced, collagen fiber deposition is obvious, and delayed-type hypersensitivity reactions is the weakest in the suture track of incisions of mice sutured by silver nanoparticle Vicryl sutures. The silver nanoparticle Vicryl sutures have potential value for clinical application.

Objective:To explore the long term efficacy of absorbable sutures coated with silver nanoparticles on the suture track of skin incisions in mice.Methods:This study was an experimental research. Eighteen half male and half female BALB/c mice aged 10-12 weeks were divided into normal Vicryl suture group, antibiotic Vicryl suture group, and silver nanoparticle Vicryl suture group according to the random number table, with 6 mice in each group, half male and half female. After the skin incisions were created on the back of all mice, the skin incisions of mice in normal Vicryl suture group, antibiotic Vicryl suture group, and silver nanoparticle Vicryl suture group were performed with continuous intradermal suture by absorbable Vicryl sutures, absorbable Vicryl sutures coated with triclosan antimicrobial, and absorbable Vicryl sutures coated with silver nanoparticles, respectively. On the 25 th day after surgery, the skin tissue in the suture track of incisions was collected, immunohistochemical staining was used to detect the percentages of F4/80, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) positive areas in the suture track of incisions of mice, the TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the percentage of TUNEL staining positive area in the suture track of incisions of mice, Masson staining was used to observe the collagen fiber formation in the suture track of incisions of mice, and immunohistochemical staining was used to detect the percentage of tissue cathepsin K positive area in the suture track of incisions of mice. The number of the above experimental samples was 6. Results:On the 25 th day after surgery, the percentages of F4/80, IL-6, and TNF-α positive areas in the suture track of incisions of mice in silver nanoparticle Vicryl suture group ((19.2±1.6)%, (20.2±1.7)%, and (16.0±1.6)%) were significantly lower than those in normal Vicryl suture group ((100±6.4)%, (100±7.6)%, and (100±9.6)%) and antibiotic Vicryl suture group ((47.2±3.2)%, (53.8±5.0)%, and 43.2%, P<0.05). The percentages of F4/80, IL-6, and TNF-α positive areas in the suture track of incisions of mice in antibiotic Vicryl suture group were significantly lower than those in normal Vicryl suture group ( P<0.05). On the 25 th day after surgery, the percentage of TUNEL staining positive area in the suture track of incisions of mice in silver nanoparticle Vicryl suture group was significantly lower than those in normal Vicryl suture group and antibiotic Vicryl suture group (with both P values <0.05). The percentage of TUNEL staining positive area in the suture track of incisions of mice in antibiotic Vicryl suture group was significantly higher than that in normal Vicryl suture group ( P<0.05). On the 25 th day after surgery, the collagen fiber deposition was not obvious in the suture track of incisions of mice in normal Vicryl suture group, no obvious collagen fiber formation was observed in the suture track of incisions of mice in antibiotic Vicryl suture group, while the collagen fibers were mostly densely arranged and well-ordered in the suture track of incisions of mice in silver nanoparticle Vicryl suture group. On the 25 th day after surgery, the percentage of tissue cathepsin K positive area in the suture track of incisions of mice in silver nanoparticle Vicryl suture group was significantly lower than those in normal Vicryl suture group and antibiotic Vicryl suture group (with P values both <0.05), the percentage of tissue cathepsin K positive area in the suture track of incisions of mice in antibiotic Vicryl suture group was significantly lower than that in normal Vicryl suture group ( P<0.05). Conclusions:In the suture track of incisions of mice, silver nanoparticle Vicryl sutures exhibit superior long-term anti-inflammatory effects compared with absorbable Vicryl sutures coated with triclosan antimicrobial and normal absorbable Vicryl sutures. Additionally, cell apoptosis is reduced, collagen fiber deposition is obvious, and delayed-type hypersensitivity reactions is the weakest in the suture track of incisions of mice sutured by silver nanoparticle Vicryl sutures. The silver nanoparticle Vicryl sutures have potential value for clinical application.

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*

BACKGROUND: More patients with pulmonary nodules are being referred to thoracic surgeons under the increasing use of computed tomography scans (CT). Impalpable peripheral subpleural solitary pulmonary nodules are difficult to be localized by video assisted thoracic surgery. Although some common techniques including CT-guided puncture positioning and electromagnetic navigation bronchoscopy (ENB)-guided methylene blue staining positioning, can bring good results in positioning, there are still some complications such as pneumothorax, hemorrhage and inaccurate positioning. Vectorial localization guided by electromagnetic navigational bronchoscopy followed by thoracoscopic resection is a novel alternative technique by us firstly for definitive diagnosis, which can avoid the possible injury of pleural or enlargement of the location area, providing some guidance for ENB-guided location technology. The main objective of this study was to evaluate the feasibility and our initial experience of vectorial localization guided by electromagnetic navigation followed by video-assisted thoracoscopic pulmonary solitary nodules resection. METHODS: We retrospectively analyzed 22 cases who undergoing vectorial localization of peripheral pulmonary lesion guided by electromagnetic navigation prior to video assisted lung resection, and characteristics and intraoperative outcomes were explored. RESULTS: Twenty-two nodules of twenty-two patients were all localized by this method successfully with an average location time (17.5±4.2) min. The average nodule size was (11.0±3.6) mm. The distance between the locatable guide probe (LG) and lesion on the electromagnetic navigation bronchoscopy screen was (14.5±10.1) mm. The distance between the lesion and probe mark on the dissected specimen was (15.3±11.0) mm. There was no displacement of any case. No conversion to thoracotomy was found. And there were no adverse events during the localization and operation procedure. Length of hospital stay was (3.8±1.2) d and the operative mortality was 0.0%. Malignant lesions were found in 19 patients and they were all completely resected with negative microscopic margins. CONCLUSIONS Our initial experience with vectorial localization of peripheral pulmonary lesion guided by electromagnetic navigation and minimally invasive resection proved that this technique was an alternative accurate and safe way for small pulmonary nodules. Thoracic surgeons should further investigate this method and apply it to clinical practice.

OBJECTIVETo detect mutations of SLC25A13 gene in 20 families affected with citrin deficiency and provide prenatal diagnosis for them.

METHODSThe 20 probands and their parents were subjected to high-frequency mutation screening combined with Sanger sequencing. After confirming the genotype of each pedigree, genetic counseling and prenatal diagnosis were performed for their subsequent pregnancies.

RESULTSBiallelic pathogenic mutations of the SLC25A13 gene were identified in all probands. These included three deletions (c.851del4, c.1092_1095delT, and c.495delA), two splice-site mutations (IVS6+5G to A and IVS11+1G to A), two nonsense mutations (c.775C to T (p.Q259X) and c.72T to A (p.Y24X)), one duplication mutation (c.1638_1660dup), one insertion (IVSl6ins3kb), and one missense mutation (c.1775A to C (p.Q592P)). Among 24 fetuses undergoing prenatal diagnosis, 8 had normal genotypes, 11 were mutation carriers, while 5 harbored biallelic mutations. Those with wild type alleles or heterozygous SLC25A13 mutations were delivered. Two fetuses harboring homozygous c.851del4 mutations were also delivered. Three fetuses harboring biallelic mutations were terminated.

CONCLUSIONAnalysis of SLC25A13 gene mutations in families affected by citrin deficiency can provide evidence for molecular diagnosis and facilitate genetic counseling and prenatal diagnosis for the subsequent pregnancy, which can effectively reduce the risk of birth of further affected children.

Objective To evaluate the correlation between serum homocysteine (Hcy) level,serum uric acid level and coronary lesion severity in patients with coronary artery disease (CAD).Methods A total of 622 patients receiving coronary angiography from January 2015 to December 2015 were retrospectively studied.They were divided into two groups according to the findings on coronary angiography.Those with ≥ 50％ stenosis were defined as coronary artery disease.According to SYNTAX score,CAD patients were divided into three groups:low risk group (1-22),moderate risk group (23-32) and high risk group (＞ 33).Fasting serum Hcy levels,fasting serum uric acid levels,fasting blood lipids including total cholesterol (TC),triglycerides (TG),high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were determined.Then,patients were divided into two groups according to the serum Hcy level for observing the relationship between the serum Hcy and the SYNTAX score.Results TC,LDL-C were significant higher in SYNTAX score high-risk group and moderate risk group compared with normal group.There were no statistically significant differences in TC and LDL-C between the normal group and the low-risk group (P ＞ 0.05).Compared with normal coronary group,Hcy in high risk group and moderate risk group was significant higher.There were no statistically significant differences in age,sex,TC,TG,HDL-C,LDL-C between normal Hcy group and high Hcy group (P ＞ 0.05).The SYNTAX score was significantly higher in high Hcy group than that in normal group (P ＜ 0.05).Multivariate logistic regression analysis suggested that serum Hcy was associated with coronary lesion severity.Compared with normal coronary group in the same gender,uric acid level in high risk group and moderate risk group was significant higher (P ＜ 0.05).Multivariate logistic regression analysis showed that serum uric acid was associated with coronary lesion severity.(P ＜ 0.05) Conclusions Serum Hcy and high uric acid level are the risk factors of coronary lesion severity.With the increased Hcy level and uric acid level,the increase in the severity degree of coronary artery lesions represents a greater cardiovascular risk.

Objective To explore the reproductive toxicity of 2,4-D butylate to the testis in male mice.Methods Forty-eight ICR male mice were randomly divided into four groups : the control group, and three 2,4-D butylate experimental groups (10, 20, 40 mg/kg), 12 mice in each group.2,4-D butylate was intragastrically administered once a day and six days per week for five weeks .At the end of the exposure, the activities of total antioxidant capacity (T-AOC), Na+ K+-ATPase, Ca+ + Mg+ +-ATPase, lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in testis homogenate were measured by spectrophotometry .Results The activity of T-AOC was gradually decreased with the increase of doses, with a significant difference between the high dose group and other groups .The activities of LDH in the moderate and high dose groups were significantly lower than those of the low dose group and control group , and there was a significant difference between the high dose group and moderate dose group .The activities of SDH in the testis was gradually decreased with the increase of the 2,4-D butylate dose, showing significant differences between the high dose group and the moderate dose and control groups , and between the high and moderate dose groups and the low dose group . The activities of Na +K +-ATPase in the moderate and high dose groups were significantly lower than that of the control and low dose group.The activities of Ca++Mg++-ATPase was significantly lower in the experimental groups than that in the control group.Conclusion Exposure to 2,4-D butylate has certain toxic effect on the testicular tissue in male mice .