The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating blood pressure and maintaining fluid balance, while clock genes are essential for sustaining biological rhythms and regulating metabolism. There exists a complex interplay between RAAS and clock genes that may significantly contribute to the development of various cardiovascular and metabolic diseases. Although current literature has identified correlations between these two systems, the specific mechanisms of their interaction remain unclear. Moreover, the interaction patterns under different physiological and pathological conditions need further investigation. This review summarizes the synergistic roles of the RAAS and clock genes in cardiovascular diseases, explores their molecular mechanisms and pathophysiological connections, discusses the application of chronotherapy, and highlights potential future research directions, aiming to provide novel insights for the prevention and treatment of related diseases.
Humans ; Renin-Angiotensin System/genetics* ; Cardiovascular Diseases/genetics* ; CLOCK Proteins/physiology* ; Animals

OBJECTIVE: To explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

OBJECTIVE To study the improvement effects of Shangke xiaoyan hydrogel plaster on osteoarthritis （OA） model rats. METHODS Rats were randomly divided into blank group， model group， voltaren group （200 mg/rat）， Shangke xiaoyan ointment group （500 mg/rat， containing Shangke xiaoyan fluid extract 50 mg） and Shangke xiaoyan hydrogel plaster group （200 mg/rat， containing Shangke xiaoyan fluid extract 50 mg）， with 8 rats in each group. Except for blank group， OA model was established in the other groups by injecting papain and L-cysteine into the right knee joint cavity of the rats； they applied the corresponding drugs， and changed the dressing once a day， for 14 consecutive days. The degree of knee joint swelling in rats was detected， and the magnetic resonance imaging characteristics of the knee joint in rats were observed； the levels of interleukin 1β （IL-1β）， IL-6， IL-18 and tumor necrosis factor （TNF- α） in rat serum were detected； the pathological and morphological characteristics of knee joint tissue were observed， and the histopathological and cartilage Mankin scores were performed； the protein expressions of IL-1β， IL-6 and TNF-α in knee joint tissue were all detected. RESULTS Compared with blank group， severe joint swelling， obvious joint effusion and patchy wear of the anterior horn of the lateral meniscus were observed in model group； the serum levels of IL-1β， IL-6， IL-18 and TNF- α and histopathological score and Mankin score were significantly increased （P＜0.05）； protein expressions of IL-1β， IL-6 and TNF-α in knee joint tissue were increased. Compared with model group， the knee swelling degree of the rats in Shangke xiaoyan hydrogel plaster group was reduced， a small amount 　　 of joint cavity effusion could be seen， and the shape of the meniscus was completely normal； the histopathological score E-mail：frankyan@cpu.edu.cn and Mankin score were significantly reduced （P＜0.05）levels of inflammatory factors in serum were reduced （P＜0.05） and those of knee tissue were decreased. CONCLUSIONS Shangke xiaoyan hydrogel plaster can improve OA of rats， the mechanism of which may be associated with reducing the levels of inflammatory factors in joint and serum.

OBJECTIVE: To compare the clinical efficacy between visual trephine arthroplasty assisted percutaneous transforaminal endoscopic discectomy (VPTED) and traditional percutaneous transforaminal endoscopic discectomy(PTED) in the treatment of lumbar disc herniation. METHODS: The clinical data of 60 patients with lumbar disc herniation admitted from June 2019 to December, 2020 was retrospectively analyzed. There were 38 males and 22 females, aged from 26 to 58 years old with an average of (43.63±8.48) years, 47 cases were on L_4,5 segment and 13 cases were on L₅S₁ segment. Among them, 32 were treated with VPTED (group A) and 28 were treated with traditional PTED (group B). The general conditions of all the patients were recorded, including intraoperative fluoroscopy times, operation time, hospital stay and surgical complications during follow-up. The arthroplasty area ratio was observed by sagittal CT at the middle level of the intervertebral foramen. Visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) score of low back pain, Oswestry disability index (ODI) were used to evaluate the clinical efficacy between two groups. RESULTS: All patients were followed up from 9 to 15 months with an average of (12.10±1.16) months. There was no statistical difference of preoperative general data between two groups. The operation time, fluoroscopy times and hospital stay were (70.47±5.87) min, (13.66±1.34) times and (6.31±0.69) d in group A, and (90.71±7.66) min, (22.82±2.48) times and (6.54±0.92) d in group B. The operation time and intraoperative fluoroscopy times in group A were lower than those in group B(P<0.05). There was no significant difference in hospital stay between two groups (P>0.05). No obvious surgical complications were found during the follow-up in both groups. The arthroplasty area ratio in group A was (29.72±2.84)% and (29.57±2.20)% in group B, respectively, with no significant difference (P>0.05). There was no significant difference in VAS, ODI and JOA score between two groups before operation and at the final follow-up(P>0.05), but the final follow-up was significantly improved(P<0.05). CONCLUSION The two surgical methods have definite clinical efficacy in the treatment of lumbar disc herniation. Visual trephine arthroplasty assisted percutaneous transforaminal endoscopic discectomy has the advantages of high efficiency and rapidity when establishing the channel, and can significantly reduce the operation time and intraoperative fluoroscopy times.
Male ; Female ; Humans ; Adult ; Middle Aged ; Intervertebral Disc Displacement/surgery* ; Retrospective Studies ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Diskectomy, Percutaneous/methods* ; Diskectomy/methods* ; Treatment Outcome ; Arthroplasty

This study aims to compare the prevalence of sexually transmitted infections (STIs) with semen quality in men from couples with primary and secondary infertility. Semen samples were collected from 133 men who requested fertility evaluation. Seminal tract infection with Ureaplasma spp. (UU), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and herpes simplex virus-2 (HSV-2) was assessed by PCR-based diagnostic assays. Among all patients, the prevalence of STIs was higher in men from couples with primary infertility than that in men from couples with secondary infertility (39.7% vs 21.7%, P = 0.03). The prevalence of UU was 28.8% and 13.3% in men from couples with primary and secondary infertility, respectively. Men from couples with primary infertility were more likely to be positive for UU than men from couples with secondary infertility (P = 0.04). Regarding the UU subtype, the prevalence of Ureaplasma urealyticum (Uuu) and Ureaplasma parvum (Uup; including Uup1, Uup3, Uup6, and Uup14) did not differ between the two groups. No associations between the prevalence rates of MH, MG, and CT were found in men from either infertility group. A lower sperm concentration was associated with STI pathogen positivity in men with primary infertility according to the crude model (P = 0.04). The crude and adjusted models showed that semen volume (both P = 0.03) and semen leukocyte count (both P = 0.02) were independently associated with secondary infertility. These findings suggest the importance of classifying the type of infertility during routine diagnosis of seminal tract infections.
Female ; Humans ; Infertility, Male/epidemiology* ; Male ; Mycoplasma genitalium ; Mycoplasma hominis ; Prevalence ; Semen ; Semen Analysis ; Sexually Transmitted Diseases/epidemiology* ; Ureaplasma urealyticum

Background: Understanding the age-related morphological changes of facial soft tissue is fundamental in achieving improved outcomes of rejuvenating procedures. Three-dimensional (3D) photogrammetry is a reliable and convenient anthropometric tool to assess facial soft tissue. Objective: The aim of this study was to establish age-related facial soft tissue morphology in Korean adult females using non-invasive 3D photogrammetry. Methods: One hundred and ninety-two female participants were divided into three groups based on age: the younger group (aged 20∼39 years), middle group (40∼59 years), and older group (60∼79 years). Thirty-six landmarks were identified via 3D photogrammetric scanning (Morpheus 3D, Morpheus Co., Ltd., Seongnam, Korea). Fortyone facial dimensions were analyzed using the imaging software to find significance between the age groups. Results: Smaller upper-facial volume (p=0.019) and shorter upperfacial height (p=0.034) were observed in the older group than in the younger group. In the mid-face, narrowed palpebral fissure (p＜0.001) with elongated upper eyelid height (p＜0.001) and widened nose (p＜0.001) were observed in the older group compared with the younger group. Longer lower-facial height (p＜0.001) with longer and wider philtrum (p＜0.001, p=0.004, respectively), shorter lower vermilion height (p＜0.001), wider mouth width (p＜0.001), and smaller lower vermilion angle (p＜0.001) were seen in the older group when compared with the younger group. Moreover, greater angles of nasofrontal, nasomental, and labiomental angle (p=0.015, p=0.015, p=0.080, respectively), and smaller nasofacial angle (p=0.034) were observed in the older group than in the younger group. Conclusion Our results provide clues of aging-related facial morphological characteristics in Korean female population.

Pulmonary fibrosis is an interstitial lung disease caused by different pathogenic factors. It has the characteristics of high morbidity and poor prognosis, which seriously affects the quality of life of patients. However, its pathogenesis has not yet been fully elucidated. Surfactant protein(SP)-A and SP-D are lipoprotein complexes distributed at the air-liquid interface of alveoli, synthesized and secreted by alveolar type Ⅱ epithelial cells and bronchiolar cells. They are important parts of the innate immune system, which participate in the host defense process through a variety of regulatory methods, and play an important role in regulating cell apoptosis and lung inflammation, promoting the process of epithelial repair and maintaining the stability of alveolar structure. The disorder and mutation of SP-A and SP-D may be the influencing factors of the pathogenesis of pulmonary fibrosis. Serum SP-A and SP-D levels are differentially expressed in patients with pulmonary fibrosis and normal healthy individuals, and are related to the severity of pulmonary fibrosis. They are considered to be a class of biomarkers that sensitively reflect lung epithelial cell damage and can be used in the diagnosis, treatment and prognostic evaluation of pulmonary fibrosis.

OBJECTIVE: To explore the mechanism of bone marrow mesenchymal stem cells(BMSCs) in alleviating silica-induced lung injury in mice. METHODS: Ten specific pathogen free healthy male C57 BL/6 mice were selected for isolating BMSCs and bone marrow macrophages(BMDMs). Transwell chamber was used, BMDMs were inoculated onto the upper chamber and BMSCs in the lower chamber. We divided them into sequencing control group and silica(SiO_2) exposure group. All cells were pre-stimulated with 50 μg/L mass concentration lipopolysaccharide for 4 hours. In the SiO_(2 ) group, 250 mg/L mass concentration SiO_2 was added to the upper chamber of transwell and cultured for 16 hours. Total RNA was extracted from the BMSCs collected from the lower chamber. HiSeq/MiSeq high-throughput sequencing technology was used to detect the BMSCs RNA paired-end sequencing. Transcriptome sequencing data was obtained and bioinformatics analysis was performed. Another 12 specific pathogen free healthy male C57 BL/6 mice were randomly divided into control group and experimental group. All mice received one intra-tracheal injection of 20.0 μL(250 g/L mass concentration) of silica dust suspension. After 6 hours, the mice in the control group was given 500.0 μL of 0.9% sodium chloride solution and mice in the experimental group was given 500.0 μL of BMSCs suspension(cell density 1×10~9/L) by tail vein infusion.Mice were sacrificed 12 hours later. The relative mRNA expression of interleukin(IL)-1 Ra, IL-10, tumor necrosis factor stimulating gene 6(TSG-6) and prostaglandin E2(PGE2) in lung tissues of mice were measured by quantitative real-time PCR(q-PCR). Meanwhile, BMDMs and BMSCs transwell co-culture models were established. The cells were divided into 5 groups: BMSCs group, BMSCs+BMDMs group, BMSCs+BMDMs+ lipopolysaccharide(LPS) group, 50 mg/L SiO_2 group, and 100 mg/L SiO_2 group. After 16 hours of corresponding SiO_2 stimulation, BMSCs of each group were collected and the relative mRNA expression levels of IL-1 Ra, IL-10, TSG-6, and PGE2 in the cells were detected by q-PCR. RESULTS: Compared with sequencing control group, BMSCs co-cultured with SiO_2 had 19 genes up-regulated and 21 genes down-regulated, including 10 genes up-regulated for more than 2.0-fold. The relative mRNA expression of IL-1 Ra, IL-10, PGE2 and TSG-6 in the lung tissue of mice increased in the experimental group than that of the control group(all P<0.05). The relative mRNA expression of TSG-6 increased by 37.5 times higher than that of the control group. Compared with the BMSCs+BMDM+LPS group, the level of TSG-6 mRNA relative expression increased in both the 50 mg/L SiO_2 group and the 100 mg/L SiO_2 group(all P<0.05). CONCLUSION: TSG-6 could be the key factor of BMSCs that can attenuate silica-induced lung injury.

OBJECTIVE: To explore the association of serum Apelin level, silicosis stage and lung function in patients with occupational silicosis(hereinafter referred to as silicosis). METHODS: A case-control study was conducted. A total of 85 patients with silicosis were selected as the silicosis group(44, 28 and 13 patients with stage Ⅰ, Ⅱ and Ⅲ silicosis, respectively), and 120 healthy individuals without occupational hazard exposure were selected as the control group. Serum samples were collected from the cases of the two groups and the level of Apelin was determined by enzyme-linked immunosorbent assay. The pulmonary function of the silicosis group was examined. RESULTS: The median and the 25 th and 75 th percentiles \[M(P_(25),P_(75))\] of serum Apelin levels in the control group and silicosis group were 1.29(0.92, 1.77) and 0.80(0.62, 1.04) mg/L, respectively. The level of serum Apelin M(P_(25),P_(75)) in stage Ⅰ, Ⅱ and Ⅲ silicosis patients was 1.03(0.82, 1.31), 0.66(0.60, 0.80) and 0.50(0.30, 0.65) mg/L, respectively. The results of multiple linear regression analysis showed that the level of serum Apelin in the silicosis group was higher than that in the control group after excluding the influence of age and smoking(P<0.01). The level of serum Apelin decreased with the increase of silicosis stage in the silicosis group(P<0.001). Serum Apelin level in silicosis group was positively correlated with lung vital capacity, forced vital capacity, forced expiratory volume in the first second, and forced expiratory flow between 25% and 75%(all P<0.05). CONCLUSION: The lower level of serum Apein in silicosis patients, the more serious the disease and the more serious the damage to lung function. Apelin is of significance in the diagnosis, staging, treatment appraisal and prognostic evaluation of silicosis, and it can be use as a potential therapeutic target for silicosis.