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 analyze the influencing factors of malaria infection of labor service exported to overseas in Langfang City, in order to establish a visualization tool to assist clinicians in predicting the risk of malaria. Methods A total of 4 774 expatriate employees of the Nibei Pipeline Project of the Pipeline Bureau from October 2021 to August 2023 were taken as the subjects, and the gender, age, overseas residence area and Knowledge of malaria controlscores of the study subjects were investigated by questionnaire survey, and the possible risk factors of malaria were screened by logistic regression model. At the same time, the nomogram prediction model was established, and the subjects were divided into the training group and the validation group at a ratio of 2:1, and the area under the curve (ROC) and the decision curve were plotted to evaluate the prediction ability and practicability of the prediction model in this study. Results Among the 4 774 study subjects, 96 cases of malaria occurred, and the detection rate was 2.01%. Junior school （OR=1.723，95% CI:1.361-2.173）， and residence in rural areas（OR=2.091，95%CI:1.760 -3.100）were risk factors (OR>1), while protective measures（OR=0.826，95% CI : 0.781 - 0.901） and high malaria education scores （OR=0.872，95% CI : 0.621 - 0.899）were protective factors.The nomogram prediction model results showed that the area under the curve of the nomogram prediction model in the training group was 0.94 (95% CI : 0.85 - 1.00), while the validation group was 0.93 (95% CI : 0.80 - 1.00). The results of the decision curve showed that when the threshold probability of the population was 0-0.9, the nomogram model was used to predict the risk of malaria occurrence with the highest net income. Conclusion The nomogram prediction model (including gender, education, region, protection and malaria education score) established and validated in this study is of great value for clinicians to screen high-risk patients with malaria.

Nine compounds were isolated and purified from 90% ethanol extract of Alstonia mairei Lévl by using various chromatographic methods, including silica gel, SephadexLH-20, MCI Gel and ODS column chromatography, combined with semi-preparative liquid phase separation methods. Modern spectroscopic methods (1D and 2D NMR, UV, IR, MS, etc.) were used to identify the structures of the isolated compounds. They were identified as mairoside A (1), 3′,6-di-O-sinaloylsucrose (2), myristic acid (3), methyl myristate (4), ethyl myristate (5), 3,4,5-trimethoxycinnamic acid (6), 3,4,5-trimethoxybenzoic acid (7), vinoline (8), kaempferol-3-O-rutinoside (9), among which compound 1 is a new glycoside, compounds 4 and 5 are new natural products, and the nuclear magnetic data of compound 4 were reported for the first time.

Objective To investigate the curative effect of suture anchor(SA)repair combined with open reduction and internal fixation(ORIF)on patients with ankle joint fracture(AF)combined with deltoid ligament injury(DLI).Methods A total of 138 patients with AF combined with DLI admitted to our hospital from January 2020 to September 2022 were selected and divided into the control group(69 cases)and the observation group(69 cases)according to the random number table method.Patients in the control group were treated with ORIF,while patients in the observation group were treated with SA repair on the basis of the control group.The clinical efficacy,American Orthopedic Foot and Ankle Society(AOFAS)score,visual analogue scale(VAS)score,talus inclination angle,medial malleolar space of affected side,bone metabolic indexes[serum bone gla protein(BGP),β-collagen degradation product(β-CTX)]levels and the incidence of complications before and 3 months after treatment were compared between the two groups.Results The total effective rate in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Compared with before treatment,the talus inclination angle,medial malleolar space of affected side,VAS score,β-CTX level 3 months after treatment of patients in the two groups were reduced,while the AOFAS score and BGP level were increased,and the differences were statistically significant(P<0.05).After treatment,the AOFAS score and BGP level in the observation group were higher than those in the control group,while the talus inclination angle and medial malleolar space of affected side were smaller than those in the control group,and the VAS score and β-CTX level were lower than those in the control group,with statistically significant differences(P<0.05).The total incidence of complications in the observation group was lower than that in the control group,and the difference was statistically significant(P<0.05).Conclusion SA repair has a definite therapeutic effect on AF combined with DLI,which can improve patients' symptoms and promote the recovery of ankle joint function and bone metabolism.

Objective:To investigate the effects of PD-1 monoclonal antibody therapy on the peripheral and local immune microenvironment of patients with microsatellite instability-high(MSI-H)rectal cancer.Methods:Samples of peripheral blood and tumor biopsy were collected from a patient with MSI-H rectal cancer before and after PD-1 monoclonal antibody treatment.The samples were dissociated into single-cell suspensions using a combination of enzymatic and mechanical methods.Immune-related marker expression on peripheral and tumor-infiltrating im-mune cells was analyzed using single-cell mass cytometry(CyTOF).Results:According to the results of CyTOF analysis,CD45+immune cells in the peripheral blood and tumor tissues were categorized into 39 and 34 cell subsets,respectively,before and after PD-1 monoclonal antibody treatment(the correlation is unclear and ambiguous).After PD-1 monoclonal antibody treatment,differences were observed in the relative abundance of immune cell subsets:B cells significantly decreased in the peripheral blood,while B cells and γδT cells significantly increased in the tumor tissue;neutrophils significantly decreased,and the proportion of CD4+TEM cells in T cell subsets significantly increased,whereas CD4+Treg cells significantly decreased.Additionally,there were differences in the expression of immune-related markers in multiple immune cell subsets in both peripheral blood and tumor tissues,with CCR6 showing a significant increase in expression across all subsets,while ICOS and PD-1 expressions in T cell subsets were significantly reduced(the specific tissues for these cells or factors are unclear).Conclusion:After PD-1 monoclonal antibody treatment in MSI-H rectal cancer,changes occurred in the composition of immune cells and the expression of immune-related markers in both peripheral blood and tumor tissues.This study reveals the dynamic adjustment of the immune microenvironment and provides important evidence for understanding the therapeutic mechanism of PD-1 monoclonal antibodies.

Objective:To evaluate the efficiency of the four domestic language models,ERNIE Bot,ChatGLM2,Spark Desk and Qwen-14B-Chat,all with a massive user base and significant social attention,in response to consultations about PCa-related perio-perative nursing and health education.Methods:We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases,and inputted the questions into each of the four language models for simulation consultation.Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy,comprehensiveness,understandability,humanistic care,and case analysis.We evaluated and compared the performance of the four models using visualization tools and statistical analyses.Results:All the models generated high-quality texts with no mis-leading information and exhibited satisfactory performance.Qwen-14B-Chat scored the highest in all aspects and showed relatively sta-ble outputs in multiple tests compared with ChatGLM2.Spark Desk performed well in terms of understandability but lacked comprehen-siveness and humanistic care.Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis.The overall performance of ERNIE Bot was slightly inferior.All things considered,Qwen-14B-Chat was superior to the other three models in con-sultations about PCa-related perioperative nursing and health education.Conclusion:In PCa-related perioperative nursing,large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support,so as to improve the patient compliance and the quality of clinical treatment and nursing.

Objective:To observe the clinical and imaging features of non-arteriotic central retinal artery occlusion (NA-CRAO) with internal boundary membrane detachment (ILMD), and to analyze its relationship with visual prognosis.Methods:A retrospective clinical study. A total of 88 patients with NA-CRAO hospitalized in Department of Ophtalmology, Xi'an People's Hospital (Xi'an Fourth Hospital) from January 2014 to June 2023 were included in the study. Best corrected visual acuity (BCVA), optical coherence tomography (OCT) and fluorescein fundus angiography (FFA) were performed. The BCVA test used the international standard visual acuity chart, which was statistically converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity. OCT observed the presence of ILMD and the thickening of the inner retina and the disappearance of anatomical stratification. FFA recorded arm-retinal circulation time (A-Rct) and retinal arterion-distal filling time (FT), and observed ciliary retinal artery, fluorescein retrograde filling, cotton spots, luciferin nodal filling, macular non-perfusion, capillary fluorescein leakage, optic disc strong fluorescence, choroidal background weak fluorescence and other characteristics. According to whether there was ILMD, the patients were divided into ILMD group and non-ILMD group, with 44 cases and 44 eyes respectively. The two groups received the same treatment. The follow-up time was 30 days after treatment. The clinical, FFA characteristics and BCVA before and after treatment were compared between the two groups. t-test was used for comparison between groups. Results:In ILMD group and non-ILMD group, there were 43 cases of male and 1 case of female, respectively, and the proportion of male was significantly higher than that of female. Before and after treatment, the logMAR BCVA of ILMD group and non-ILMD group were 2.35±0.42, 2.01±0.46, 1.47±0.60, 0.77±0.49, respectively. There were significant differences in logMAR BCVA between the two groups before and after treatment ( t=8.025, 12.358; P<0.001). Before treatment, A-Rct and FT in ILMD group were longer than those in non-ILMD group, and the difference was statistically significant ( t=3.052, 3.385; P<0.05). After treatment, there was no significant difference ( t=1.040, 1.447; P >0.05). The proportion of ciliary retinal artery and cotton plaque in ILMD group was lower than that in non-ILMD group. There was no significant difference in ciliary retinal artery between the two groups ( χ2=-0.961, P>0.05), but there was a significant difference in cotton wool plaque between the two groups ( χ2=-3.364, P <0.05). Compared to the non-ILMD group, The proportion of retrograde fluorescein filling in retinal artery ( χ2=-2.846), segment filling ( χ2=-3.907), macular non-perfusion ( χ2=-6.656), capillary fluorescein leakage ( χ2=-4.367), optic disc strong fluorescence ( χ2=-3.525) and choroidal background weak fluorescence ( χ2=-2.276) increased, the difference was statistically significant ( P<0.05). Conclusions:In patients with NA-CRAO, compared with those without ILMD, those with ILMD have more severe retinal ischemia and worse BCVA before and after treatment. ILMD is one of the poor prognostic markers of NA-CRAO vision.

The current situation of artificial intelligence(AI)was introduced when applied in the key links of cardiovascular health management such as risk prediction,early screening,clinical decision support and health consultation and education.The deficiencies of AI during the application were analyzed,and the prospects and development directions of AI in cardiovascular health management were pointed out.[Chinese Medical Equipment Journal,2024,45(2):92-96]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To evaluate the in vitro effect of combinations of 5 β-lactam antibiotics with different β-lac-tamase inhibitors on the activity of multidrug-resistant Mycobacterium tuberculosis(MDR-TB),and identify the most effective combination of β-lactam antibiotics and β-lactamase inhibitors against MDR-TB.Methods MDR-TB strains collected in Henan Province Antimicrobial Resistance Surveillance Project in 2021 were selected.The mini-mum inhibitory concentrations(MIC)of 5 β-lactam antibiotics or combinations with different β-lactamase inhibitors on clinically isolated MDR-TB strains were measured by MIC detection method,and the blaC mutation of the strains was analyzed by polymerase chain reaction(PCR)and DNA sequencing.Results A total of 105 strains of MDR-TB were included in the analysis.MIC detection results showed that doripenem had the highest antibacterial activity against MDR-TB,with a MIC50 of 16 μg/mL.MIC values of most β-lactam antibiotics decreased significantly after combined with β-lactamase inhibitors.A total of 13.33％(n=14)strains had mutations in blaC gene,mainly 3 nu-cleotide substitution mutations,namely AGT333AGG,AAC638ACC and ATC786ATT.BlaC proteins Ser111 Arg and Asn213Thr enhanced the synergistic effect of clavulanic acid/sulbactam and meropenem on MDR-TB compared with synonymous single-nucleotide mutation.Conclusion The combination of doripenem and sulbactam has the strongest antibacterial activity against MDR-TB.Substitution mutations of BlaC protein Ser111 Arg and Asn213Thr enhances the sensitivity of MDR-TB to meropenem through the synergy with clavulanic acid/sulbactam.