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.

Objective: To explore the relationship of physical exercise behavior with mobile phone addiction and mental health of college students, so as to provide evidence for interventions to improve mobile phone addiction and mental health of college students. Methods: From October 8 to December 20 in 2024, 896 college students from 4 colleges in Beijing were selected using a combination of convenience sampling and stratified random cluster sampling method. Physical Activity Rating Scale (PARS-3), Mobile Phone Addiction Tendency Scale (MPATS), Adolescence Mental Health Diathesis Questionnaire (AMHDQ) and Symptom Checklist 90 (SCL-90) were used. The correlation of mobile phone addiction and mental health on physical exercise behavior of college students were analyzed by multivariable Logistic regression and linear regression. Results: Among the surveyed college students, 504 (56.25%) students had low exercise, 262 (29.24%) had moderate exercise, 130 (14.51%) had high exercise, and 392 (43.75%) had sufficient exercise. The total score of PARS-3 was 18.00 ( 15.00 , 33.00) points. Logistic regression analysis showed that the total score of MPATS ( OR=1.022, 95%CI =1.008-1.036), the total score of SCL-90 ( OR=1.010, 95%CI = 1.005 -1.015), the total AMHDQ score ( OR=0.995, 95%CI =0.992-0.998) were significantly associated with insufficient exercise among college students ( P <0.05). Linear regression analysis showed that the scores of MPATS, AMHDQS and SCL-90 were significantly correlated with physical exercise behavior ( B=-0.20, 0.04, -0.07, P <0.05). Conclusion The physical exercise behavior of college students is related to mobile phone addiction and mental health.

Objective:To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM)with mSMART 3.0 score.Methods:Clinical data were collected from 16 patients with mSMART3.0 score high-risk relapsed refractory MM treated at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to May 2023,all of whom received daltezumab-based regimen(regimen drugs including dexamethasone,isazomib,bortezomib,lenalidomide).The efficacy and safety of the treatment were retrospectively analyzed.Results:The median age of 16 patients was 63.5(47-70)years old,including 10 cases of IgG type,2 cases of IgA type,and 4 cases of light chain type.The curative efficacy was judged in all 16 patients,with an overall response rate of 93.75％(15/16),including 4 cases of strict complete remission(sCR),1 case of complete remission(CR),2 case of very good partial remission(VGPR),partial remission(PR)in 5 cases,and minor remission(MR)in 3 cases.The median follow-up time was 11(2-30)months,and the median progression-free survival and median overall survival were not achieved in 16 patients at the median follow-up period.The hematologic adverse effects of the treatment regimen using daratumumab-based were mainly neutropenia,and the non-hematologic adverse effects were mainly infusion-related adverse reactions and infections.Conclusion:Daratumumab-based regimen for the treatment of relapsed refractory MM patients with high risk of mSMART3.0 score has better efficacy and safety.

AIM To study the effects of Liangxue Heying Formula on vascular inflammatory injury in a rat model of thromboangiitis obliterans(TAO).METHODS The rats were randomly divided into the sham operation group,the model group and the low,medium and high dose Liangxue Heying Formula groups(2.25,4.5,9 g/kg).With the rat TAO model successfully established by injection of 0.1 mL sodium laurate(10 mg/mL)into the femoral artery of hind limbs,corresponding doses of drugs by gavage were administered upon the rats.Subsequently,the rats had their morphological changes of the affected limbs observed and assessed;their changes of blood flow in hind limbs scanned by laser Doppler flowmetry;their plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1 detected by ELISA;their histopathological changes of femoral artery and vein observed by HE staining;and their protein expressions of TNF-α,IL-6,JAK2,p-JAK2,STAT3,p-STAT3,ICAM-1 and VCAM-1 in femoral artery detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased morphological score of the affected limb(P＜0.01);decreased blood perfusion ratio of the affected side/healthy side(P＜0.01);increased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P＜0.01);more existence of thrombotic infiltration containing a larger number of inflammatory cells in femoral artery and femoral vein tissue,and increased protein expressions of TNF-α,IL-6,p-JAK2,p-STAT3,ICAM-1 and VCAM-1 in femoral artery(P＜0.01).Compared with the model group,the medium and high dose Liangxue Heying Formula groups demonstrated decreased morphological score of the affected limb(P＜0.01);increased blood perfusion ratio of the affected side/healthy side(P＜0.01);reduced infiltration of thrombus and inflammatory cells in femoral artery and femoral vein tissue,and decreased protein expressions of IL-6 and p-STAT3 in femoral artery tissue(P＜0.01).All Liangxue Heying Formula groups shared decreased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P＜0.05,P＜0.01);and reduced protein expressions of TNF-α,ICAM-1,VCAM-1 and p-JAK2 in femoral artery(P＜0.01).CONCLUSION Liangxue Heying Formula can improve the systemic inflammatory state of TAO rats by inhibiting the activation of endothelial cells and reducing vascular inflammatory injury possibly due to the mechanism associated with the regulation of the JAK2/STAT3 signaling pathway.

The World Health Organization (WHO) classification serves as the internationally recognized standard for diagnosing and classifying hematopoietic and lymphoid tissue tumors(WHO-HEAM). Since 2001, it has undergone multiple upgrades and revisions, updating, clarifying, and refining previous tumor diagnostic and classification standards while incorporating numerous new genetic and molecular biological subtypes. In 2022, two classification proposals emerged due to a wealth of clinical and scientific research results: the fifth edition of the WHO hematopoietic and lymphoid tissue classification (WHO-HAEM5), published in Leukemia journal; and the International Consensus Classification (ICC), published in Blood journal. These two schemes differ in their approach to classifying hematopoietic and lymphoid tissue tumors, posing challenges for clinical laboratory diagnosis and treatment.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg^-1） group， and low- and high-dose （8.4 and 33.6 g·kg^-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.

Objective To evaluate the efficacy of vitamin C intravenous injection in the treatment of patients with sepsis.Methods PubMed,Embase,Scopus,Cochrane Library,and Clinical Trial databases were retrieved,with a retrieval period from database establishment to December 2022.English literatures on randomized controlled trial(RCT)of vitamin C intravenous injection for the treatment of sepsis or septic shock were collected.Meta-analysis was conducted using RevMan 5.3 software and Stata 15.0 software after literature screening,extraction,and evalua-tion of the bias risk included in the studies by two researchers independently.Results A total of 16 RCT studies involving 3 301 patients were included in the analysis.In terms of main outcomes,the 28-day mortality of patients in the vitamin C treatment group was slightly lower than that of the control group,but the difference was not statis-tically significant(RR=0.86,95％CI[0.72-1.03],P=0.10;I2=44％,P=0.10).In terms of secondary out-comes,vitamin C intravenous injection can reduce the duration of vasoactive drug usage time(MD=-23.44,95％CI[-30.53--16.35],P＜0.01;I2=0,P=0.97),but has no significant effect on the 90-day mortality,inten-sive care unit mortality,hospital mortality,duration of mechanical ventilation,difference in estimated sequential organ failure assessment score at 72 hour,length of stay in ICU,and total length of hospital stay of patients(P＞0.05).Conclusion Intravenous vitamin C injection can significantly reduce vasoactive drug usage time,but the available evidence is insufficient to support that intravenous vitamin C can improve the prognosis of patients with sepsis or septic shock.More high-quality,multicenter randomized controlled trial is needed to provide more substantial evidence about the efficacy of vitamin C in treating sepsis or septic shock.

Acute respiratory distress syndrome (ARDS) is severe respiratory failure in clinical practice, with a mortality rate as high as 40%. Injury of pulmonary endothelial cells and alveolar epithelial cells occurs during ARDS, and pulmonary endothelial injury results in endothelial barrier disruption, which usually occurs before epithelial injury. Especially, when harmful factors enter the blood, such as sepsis and hemorrhagic shock, the pulmonary endothelial cells are affected firstly. The injured endothelial cells may loss cell-to-cell connections and even die. After the endothelial barrier is disrupted, fluid and proteins cross the endothelial barrier, causing interstitial edema. The alveolar epithelium is more resistant to injury, and when the tight barrier of the epithelium is broken, fluids, proteins, neutrophils, and red blood cells in the interstitium enter the alveolar space. From this process, it is easy to find that the endothelium is the first barrier to prevent edema, therefore, the protection of endothelium is the key to the prevention and treatment of ARDS. In addition, the injured endothelial cells express selectin and cell adhesion molecules, promoting the recruitment of immune cells, which exacerbate the inflammatory response and pulmonary endothelial cell injury. Mesenchymal stem cells (MSCs) can be derived from umbilical cord, bone marrow, adipose and so on. Because of low immunogenicity, MSCs can be used for allogeneic transplantation and have great application potential in tissue repairing. Through paracrine effect, MSCs can promote cell survival and balance inflammatory response. MSCs infused intravenously can locate in lungs rapidly and interact with endothelial cells directly, thus MSCs have advantages in protecting pulmonary microvascular endothelial cells. Animal experiments and clinical trials have found that MSC transplantation can significantly improve the symptoms of ARDS and reduce inflammatory reactions and endothelial permeability. Mechanically, MSCs acts mainly through paracrine and immunomodulatory effects. Paracrine cytokines from MSCs can not only promote pulmonary endothelial proliferation, but also reduce inflammatory response and promote cell survival to maintain endothelial integrity. In addition to paracrine cytokines, extracellular vesicles of MSCs are rich in RNAs, proteins and bioactive substances, which can protect pulmonary endothelial cells by intercellular communication and substance transport. Furthermore, MSCs may protect pulmonary endothelial cells indirectly by regulating immune cells, such as reducing the formation of extracellular trapping network of neutrophils, regulating macrophage polarization and regulating Th17/Treg cell balance. Although the beneficial effects of MSCs are verified, much work still needs to be done. MSCs from different tissues have their own characteristics and the scope of application. Different lung diseases possess different endothelial injury mechanisms. Thus, determining the indications of MSCs derived from different tissues is the direction of pulmonary disease clinical trials. From the perspective of transplantation route, intravenous injection of MSCs may have better clinical application in pulmonary endothelial injury caused by endogenous harmful factors in blood. Previous reviews mostly focused on the protective effects of MSCs on alveolar epithelium. In this article, we focused on endothelial cells and reviewed the direct protective effects and mechanisms of MSCs on endothelium through paracrine cytokines and extracellular vesicles, and summarize the mechanisms by which MSCs may indirectly protect pulmonary endothelial cells by regulating immune cells.