Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

ObjectiveTo study the effect and mechanism of Yixintai on mitochondrial fission proteins in the rat model of chronic heart failure. MethodTen of 60 SD rats were randomly selected as the sham operation group， and the remaining 50 rats were subjected to ligation of the left anterior descending coronary artery for the modeling of heart failure post myocardial infarction. The successfully modeled rats were randomized into model， low-， medium-， and high-dose （1.4， 2.8， and 5.6 g·kg^-1， respectively） Yixintai， and trimetazidine （10 mg·kg^-1） groups. The rats were administrated with corresponding doses of drugs by gavage， and the rats in the model group and sham operation group were given an equal volume of normal saline by gavage for 28 consecutive days. Enzyme-linked immunosorbent assay （ELISA） was then employed to measure the levels of amino-terminal pro-B-type natriuretic peptide （NT-pro BNP）， B-type natriuretic peptide （BNP）， and adenosine triphosphate （ATP） in the serum. Color Doppler ultrasound imaging was conducted to examine the cardiac function indicators. Hematoxylin-eosin staining and Masson staining were conducted to observe the pathological changes in the heart， and Image J was used to calculate collagen volume fraction （CVF）. Transmission electron microscopy was employed to observe the ultrastructural changes of myocardial cells. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to measure the apoptosis rate of myocardial cells. Western blot was employed to determine the protein levels of mitochondrial fission protein 1 （Fis1） and mitochondrial fission factor （Mff） in the outer mitochondrial membrane of the myocardial tissue. ResultCompared with the sham operation group， the model group showed elevated levels of NT-pro BNP and BNP in the serum， decreased ATP content， left ventricular ejection fraction （LVEF）， and left ventricular fraction shortening （LVFS）， increased left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs）， disarrangement of myocardial cells， inflammatory cell infiltration， increased collagen fibers and CVF， damaged myocardium and mitochondria， and increased apoptosis rate of myocardial cells， and up-regulated expression of Fis1 and Mff in the cardiac tissue （P<0.01）. Compared with the model group， different doses of Yixintai and trimetazidine lowered the serum levels of NT-pro BNP and BNP （P<0.05）， increased the ATP content （P<0.05）， increased LVEF and LVFS （P<0.01）， decreased LVIDd and LVIDs （P<0.01）. Moreover， the drugs alleviated the myocardial inflammatory damage and fibrosis， reduced CVF （P<0.01）， repaired the myocardial mitochondrial structure， and decreased the apoptosis rate of myocardial cells （P<0.01）. Medium- and high-dose Yixintai and trimetazidine down-regulated the expression of Fis1 and Mff in the myocardial tissue （P<0.05）. ConclusionYixintai can improve mitochondrial structure， reduce myocardial cell apoptosis， and improve cardiac function by inhibiting the expression of Fis1 and Mff in the myocardial tissue.

Neoantigen pulsed dendritic cell vaccine(Neo-DCVac)is a new type of tumor immunotherapy.Neoantigen is strong immunologic and tumor-specific mutated peptides expressed in a tumor.Neo-DCVac is a therapeutic modality based on the uptake and processing of neoantigens by dendritic cells and their delivery and activation of T cells to trigger the body's immune response for anti-tumor effects.The development of individualized Neo-DCVac based on high-throughput sequencing is expected to be a new direction for precision immunotherapy of tumors.In this review,we discuss construction of individualized Neo-DCVac,clinical application of combination therapy in solid tumors,suitable population for vaccination and the current limitations of Neo-DCVac,aiming to provide a theoretical reference for research on tumor immunotherapy.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To observe the application effect of intra-arterial tirofiban during mechanical thrombectomy for acute anterior circulation cerebral infarction.Methods The clinical data of patients with acute anterior circulation cerebral infarction were retrospectively analyzed.According to cohort method,they were divided into control group and treatment group.The control group was treated with mechanical thrombectomy,while the treatment group was additionally given intra-arterial therapy with tirofiban 0.25-0.5 mg on the basis of the control group.The perioperative indicators(surgical time,number of thrombectomy,vascular recanalization time,vascular recanalization rate),National Institutes of Health Stroke Scale(NIHSS)score before treatment and at 24 hours and 7 days after treatment,platelet indicators[mean platelet distribution width(PDW),mean platelet volume(MPV),plateletcrit(PCT)],hemorheological indicators[plasma viscosity(PV),low whole blood viscosity(LWBV),high whole blood viscosity(HWBV)],serum indicators[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),vascular endothelial growth factor(VEGF)]and clinical efficacy were compared,and the safety of the treatment regimen was assessed.Results There were 92 patients were finally included in this study,including 49 cases in control group and 43 cases in treatment group.The effective rates in treatment group and control group were 75.51％(37 cases/49 cases)and 93.02％(40 cases/43 cases),with significant difference(P＜0.05).The surgical times in treatment group and control group were(93.53±9.86)and(91.59±8.36)min;the vascular recanalization times were(78.46±9.69)and(77.40±10.32)min;the vascular recanalization rates were 93.02％and 83.67％;the NIHSS scores were(10.32±2.90)and(9.59±2.84)points at 24 hours after treatment,all with no significant difference(all P＞0.05).At 7 days after treatment,the NIHSS scores in treatment group and control group were(3.34±1.25)and(4.12±1.48)points;the PDW values were(12.58±1.81)％and(14.15±1.95)％;MPV values were(9.16±1.24)and(11.26±1.86)fL;PCT levels were(0.33±0.05)％and(0.29±0.04)％;PV values were(1.64±0.27)and(1.99±0.24)mPa·s-1;LWBV values were(4.16±0.48)and(5.01±0.49)mPa·s-1;HWBV values were(8.12±0.54)and(9.27±0.68)mPa·s-1;serum hs-CRP levels were(3.57±0.45)and(4.48±0.83)mg·L-1;TNF-α levels were(20.42±4.55)and(27.34±4.95)ng·L-1;VEGF levels were(738.80±52.41)and(664.72±41.68)ng·L-1,all with significant difference(all P＜0.05).Incidence rates of adverse drug reactions in treatment group and control group were 8.16％(4 cases/49 cases)and 4.65％(2 cases/43 cases)respectively,with no significant difference(P＞0.05).Conclusion Intra-arterial tirofiban therapy during thrombectomy for acute anterior circulation cerebral infarction has good neurological function and prognosis,and it may be related to the improvement of platelet function and cerebral tissue blood flow and relief of inflammatory response.

The chimeric antigen receptor T cell(CAR-T)therapy products approved for market and under development mainly targets the B-cell receptor-related protein CD19.This paper relies on the pharmacovigilance database during clinical trials of the Center for Drug Evaluation National Medical Products Administration.We retrospectively analyzed the 113 individual case safety expedited reports of suspected unexpected serious adverse reactions of CAR-T cell therapy products containing B-cell receptor-rolated protein CD19 from domestic clinical trials received from January 1,2021 to May 20,2024.Strengthen risk management according to product characteristics.It is expected that through this paper,the sponsors can improve the pharmacovigilance regime and system,timely report according to the requirements,strengthen the risk communication with the regulatory authorities,form a joint force with the regulatory authorities,and jointly do a good job in risk management during clinical trials.

Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90％confidence interval(CI)of the geometric mean ratio(GMR)were 94.11％-118.06％,99.22％-107.74％and 99.16％-107.44％for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00％-125.00％.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90％CI of GMR were 96.99％-101.19％and 97.17％-101.41％for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00％-125.00％.The 95％upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00％-125.00％.The incidence of adverse events in fasting and fed studies was 22.86％and 22.92％,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.

In recent years,chimeric antigen receptor T cell(CAR-T)therapeutic products have shown good efficacy in the treatment of blood tumors,and breakthroughs have also been made in the treatment of solid tumors and autoimmune diseases.In order to further understand the clinical research and development progress of CAR-T products,this paper mainly uses the drug clinical trial registration and information publication platform of the Center for Drug Evaluation National Medical Products Administration as the information source,and focuses on the statistical analysis of the clinical trial progress of domestic CAR-T cell therapy products containing the targeted B-cell receptor-related protein CD19.It is hoped to further improve the quality and efficiency of clinical research and development of CAR-T cell therapy products,strengthen the sponsor's awareness of main responsibility,and timely update trial information to protect the rights and interests of subjects during clinical trials.