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 mechanism of Fasudil reducing Aβ1-42 induced BV2 cell injury based on NLRP3 inflamma-some.Methods:BV2 cells were divided into:normal control group,Aβ stimulation group,Aβ+Fasudil intervention group,Aβ+MCC950(NLRP3 inhibitor)intervention group.Cell morphology was observed under microscope.Cell activity was determined of by CCK8.NO release was measured by Griess.NLRP3,caspase 1 and IL-18 expressions were detected by immunofluorescence staining.NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were detected by Western blot.Results:Compared with normal control group,BV2 cells in Aβ stimulation group were activated and showed amoeba-like shape,cell activity was decreased,NO production was increased,NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were increased.Fasudil intervention and MCC950 intervention inhibited cell injury induced by Aβ1-42 in which BV2 cell morphology tended to be normal,cell activity was increased,while produc-tion of NO was reduced,and NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were down-regulated,there was no significant difference between Fasudil intervention group and MCC950 intervention group.Conclusion:Fasudil may alleviate Aβ1-42 induced BV2 cell injury and inflammatory reaction by inhibiting NLRP3 inflammasome activation.

Objective To investigate the regulatory mechanism of Notch signaling pathway by YAP in non-alcoholic steatohep-atitis(NASH)liver fibrosis,and assess the intervention effect of Cigu Xiaozhi prescription in detoxification and phlegm treatment.Methods C57BL/6J mice were randomly divided into different groups,including a normal group,NASH liver fibrosis model group,verteporfin(VP)intervention group,VP+Chinese medicine(Cigu Xiaozhi prescription)low-dose group,VP+Chinese medicine high-dose group,and dimethyl sulfoxide control group.The methionine/choline-deficient diet combined with low-dose CCl4 was used to construct the NASH liver fibrosis model.The degree of liver fibrosis was evaluated using hematoxylin and eosin(HE)and Masson staining.Four protein factors associated with liver fibrosis were detected using enzyme-linked immunosorbent assay,and hydroxyproline levels in the mouse liver was determined using the alkaline water method.The localization of α-SMA,ColⅠ,YAP,and Notch1 proteins in the liver was determined using immunohistochemistry.Additionally,the mRNA and protein expression levels of the Notch signaling pathway molecules,namely Notch1/2,J agged1,and DLL4,were assessed using real-time quantitative PCR and Western blotting analyses,respectively.Results The HE and Masson staining results revealed that the liver cells of NASH liver fibrosis mice were swollen and the cytoplasm was transparent.Additionally,evident fibrosis was observed in the hepatic lobule,portal area,and sinus;it was accompanied by heightened levels of inflam-matory cell infiltration,a large number of fat droplets,and instances of local hepatocyte necrosis,dissolution,and cirrhosis.The four factors associated with liver fibrosis showed a substantial increase(P<0.01).α-SMA,ColⅠ,YAP,and Notch1 were localized in the cytoplasm of hepatocytes.YAP,Notch1/2,and Jagged1 were highly expressed in the liver(P<0.01)but were downregulated after intervention with VP and VP+high and low doses of Cigu Xiaozhi prescription(P<0.05).Meanwhile,DLL4 factor was upregulated in the VP+high-dose of Cigu Xiaozhi prescription group(P<0.05).Conclusion YAP may inhibit activation of the Notch pathway by downregulating Notch1/2 and Jagged1 and upregulating DLL4,thereby interfering with the occurrence of liver fibrosis in NASH.Treatment with Cigu Xiaozhi pre-scription may inhibit Notch signaling pathway activation by downregulating YAP,Notch1/2,and Jagged1 and upregulating DLL4 through its multi-components and multi-targets properties,ultimately slow the progression of liver fibrosis in NASH.

Objective:To explore the clinical effect of perforator pedicled propeller flap (PPPF) in reconstruction of soft tissue defect in ankle and foot, as well as the role of preoperative ultrasonography in assistance of the location of perforators in donor site.Methods:From January 2017 to June 2023, the Department of Microorthopedics of the Second Affiliated Hospital of Luohe Medical College of Higher Education applied PPPF to reconstruct small and medium-sized soft tissue defects in the ankle and foot for 26 patients. The patients were 17 males, 9 females, aged 18 to 68 years old with 46 years old in average. The defect sites were 3 in forefoot and 6 in midfoot and combined with different degrees of tendon and bone exposure, 17 in ankle and heel and combined with various degrees of bone exposure, 12 with ankle open injury and 5 with Achilles tendon exposure. The area of soft tissue defects ranged from 2.5 cm×1.5 cm to 16.0 cm × 6.5 cm. The width of injury was measured before surgery, and a HHD was used to detect the perforators proximal to the defect site, and then high-frequency CDU was used to locate and confirm the location of the perforator and its alignment, blood flow and diameter. The line drawn between the 2 perforators was set as the axis of flap. The donor site was assessed by a "pinching and lifting" method to determine a direct closure of donor site or to have it closed by a flap transfer. The sizes of flap were from 2.8 cm×1.5 cm to 24.0 cm×7.5 cm. Twenty-two donor sites were directly closed and 4 received flap transfers. Four flaps had sutures with the skin nerves in the recipient site. Masquelet technique was performed in 6 patients with bone defects in the surgery. Patients received outpatient reviews with 1-2 weeks of intervals in the first 2 months after surgery, and X-ray reviews per 1-2 months for those with bone implants until bone healing.Results:All flaps survived successfully without any special treatment after surgery, except 1 flap that had blood vessel congestion and showed swelling and poor blood supply to the distal flap at 24 hours after surgery. The blood vessel congestion was revised by removal of part of the suture at the tip of flap pedicle. One week later, the tip of the flap remained with a small area of necrosis, which was then healed after dressing changes. A total of 21 patients were included in postoperative follow-up with 4 months to 3 years. All of the flaps had satisfactory appearance, colour and texture, and without any ulceration. Three cases of nerve suture were also included in follow-up. According to the assessment criteria of British Medical Research Council (BMRC), the sensory recovery of the flaps was found of S 2 in 1 flap and S 3 in 2 flaps. According to the American Orthopaedic Foot and Ankle Society (AOFAS), the ankle-hindfoot function scores, there were excellent in 16 patient and good in 5 patients. Conclusion:With the assistance of ultrasound, the PPPF can be effectively used in reconstruction of soft tissue defects in ankle and foot.

Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess anti-insomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein,we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry(LC-MS/MS)-based pharmaco-metabolomics and mass spectrometry imaging(MSI)-based spatial resolved metabolomics.According to the results,17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain,which might be the major components contributing to the sedative-hypnotic effects.Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction,serotonergic synapse,dopaminergic synapse,and dopaminergic synapse,among other pathways.LC-MS/MS-based targeted metabolomics and Western blot(WB)revealed that tryptophan-serotonin-melatonin(Trp-5-HT-Mel)and tyrosine-norepinephrine-adrenaline(Tyr-Ne-Ad)are the key regulated pathways.Dopa decarboxylase(DDC)upregulation and phenylethanolamine N-methyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.

Purpose To construct the model of differentiating primary central nervous system lymphoma(PCNSL)and atypical glioblastoma(GBM)by combining multi-parameter MRI radiomics and six machine learning algorithms,thus to compare the diagnostic efficacy of different machine learning algorithms.Materials and Methods The clinical and imaging data of 77(125 lesions)PCNSL and 90 atypical GBM(108 lesions)from PLA General Hospital and public databases were retrospectively analyzed from January 2013 to December 2023,and all patients were randomly divided into a training set(163 cases)and a validation set(70 cases)according to 7∶3.T1WI,T2WI and T1-weighted contrast-enhanced sequences were selected for tumor segmentation,and 1 132 radiomics features were extracted from each region of interest.The intraclass correlation coefficient(ICC)was used for the consistency test,and image features with ICC≥0.85 were selected.ICC and recursive feature elimination were used to select the best radiomics features.Six classifiers were used to train and verify three single sequence feature sets,three double-sequence sets and one multi-sequence set.The receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the model.Results The combination model of the support vector machine of radial basis function classifier and multi-sequence feature set were the best model for differentiating PCNSL and atypical GBM.The area under the curve of the training set and the validation set were 0.969 and 0.913,respectively;and the accuracy were both 0.886.Conclusion Noninvasive extraction of multiparametric MRI features combined with machine learning algorithms can effectively differentiate PCNSL and atypical GBM,which provides support for the development of individualized treatment plans for patients.

ObjectiveTo investigate the effect of Yiqi Tongxin formula （YQTM） on liver inflammation in apolipoprotein E^-∕- （ApoE^-∕-） mice by regulating the nuclear transcription factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway. MethodForty ApoE^-∕- mice were randomly divided into a model group， an atorvastatin group （positive drug group）， and low-， medium-， and high-dose YQTM groups （0.39， 0.78， 1.56 g·kg^-1）. Each drug administration group was given the corresponding concentration of the drug by gavage on the basis of high-fat feeding for 12 consecutive weeks. Eight C57BL/6J mice were used as a blank group and fed with normal chow. After 12 weeks， oil red O staining and Masson staining were used to observe the aortic lesions in mice and to determine whether the modeling was successful. Oil red O staining was used to observe the lipidosis in the livers of mice. Hematoxylin-eosin （HE） staining was used to observe the tissue lesions in the livers of mice. Masson staining was used to observe the distribution of collagen fibers in the livers of mice. Enzyme markers were used to detect the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in mouse serum， as well as total cholesterol （TC） and triglyceride （TG） in the liver. Interleukin-1β （IL-1β） and IL-18 were detected in mouse liver by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was utilized to observe the expression regions of NF-κB and NLRP3 in the livers of mice. Western blot was employed to detect the protein expression levels of NF-κB， NF-κB inhibitory protein （IκB）， IκB kinase β （IKKβ）， phosphorylated NF-κB （p-NF-κB）， phosphorylated IκB （p-IκB）， phosphorylated IKK β （p-IKKβ）， NLRP3， and Caspase-1 in the livers of mice. ResultCompared with the blank group， the model group showed severe aortic lipidosis， and the intracellular fat droplets in the livers aggregated in large quantities. The cytoplasm was filled with fat vacuoles（P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly elevated in the mice（P<0.01）. TG and TC levels were elevated in the liver（P<0.01）. The levels of IL-1β and IL-18 in liver tissue， as well as the protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly elevated（P<0.01）. Compared with the model group， the aortic arch plaques of mice in each YQTM group were attenuated， and the fat aggregation in the liver was reduced. The inflammatory cell infiltration was alleviated（P<0.05，P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly reduced（P<0.05，P<0.01）. TG and TC levels in the liver were reduced. The IL-1β and IL-18 levels in liver tissue， as well as protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly reduced（P<0.05，P<0.01）. ConclusionThe intervention mechanism of YQTM on liver inflammation in ApoE^-∕- mice may be related to the down-regulation of the NF-κB/NLRP3 signaling pathway.

Hepatocellular carcinoma （HCC） is a common tumor in the digestive tract， the formation mechanism of which remains to be fully elucidated. Although surgery， radiation， chemotherapy， targeted therapy， and immunotherapy have achieved significant results in the treatment of HCC， these methods are accompanied by a considerable number of adverse reactions and complications. In recent years， Chinese medicine has shown remarkable efficacy in the treatment of HCC， and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine， which exerts therapeutic effects via multiple components and multiple targets. However， the pathogenesis of HCC is exceptionally complex and not fully understood， which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Hedgehog， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and transforming growth factor-β （TGF-β）/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis， inhibiting cell proliferation and migration， and blocking the cell cycle via the above pathways. However， the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets， new perspectives， and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.

Objective To explore the clinical characteristics and risk factors of death during hospitalization in patients with community-acquired pneumonia(CAP)complicated with diabetes mellitus(DM).Methods A retrospective analysis was performed on 566 patients with CAP hospitalized in the Second Affiliated Hospital of Kunming Medical University from January 2018 to January 2022.The patients were divided into simple CAP group(n=478)and CAP combined with diabetes(CAP+DM)group(n=88)according to whether they had diabetes,and then CAP+DM group(n=88)was divided into survival group(n=69)and death group(n =19)according to whether the patients died during hospitalization.The clinical data and laboratory test indicators of patients in different groups were compared.Cox regression analysis was used to screen the risk factors of death during hospitalization in the CAP+DM group.Receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of independent risk factors on hospitalization death.Results Compared with the simple CAP group,the CAP+DM group had significant differences in age,concomitant hypertension,coronary heart disease,CURB-65 score,neutrophil to lymphocyte ratio(NLR),C-reactive protein(CRP),procalcitonin(PCT),albumin(ALB),prealbumin(PA),glucose(GLU),serum potassium(K),calcium(Ca),phosphorus(P),magnesium(Mg),lactic acid(Lac),non-invasive ventilation time,ICU occupancy rate and mortality rate(P<0.05);Compared with the survival group,there were statistically significant differences in CURB-65 score,NLR,CRP,PCT,GIU,ALB,PA,serum iron(Fe),Ca,non-invasive ventilation time,and ICU admission rate among the death group patients(P<0.05).Cox regression analysis showed that the increase of NLR level and the decrease in PA level were the risk factors for in-hospital death in patients with CAP complicated with diabetes(P<0.05).When the PA cutoff value was 91 mg/L,the AUC,sensitivity,and specificity for predicting in-hospital death of CAP patients with diabetes were 0.849,84.2%and 81.2%,respectively.Conclusion Patients with CAP combined with diabetes are more serious and have worse prognosis than those with CAP alone.PA has a good predictive value for the prognosis of these patients.Early detection and active intervention should be carried out to reduce the in-hospital mortality of patients.

Objective:To explore the effect of family empowerment model on the improvement of swallowing care ability and care preparedness of primary caregivers of first-episode stroke dysphagia patients, further to explore its impact on patients′s wallowing function and life quality.Methods:This study was a randomized controlled study. From January 2021 to December 2022, 80 main caregivers of patients with dysphagia caused by manual stroke admitted to the Department of Acupuncture and Moxibustion, Shenzhen Hospital of Traditional Chinese Medicine were selected as the research objects, and 40 cases in the control group and 40 cases in the observation group were selected by random number table method. The control group were treated with conventional nursing care of first-episode stroke dysphagia patients in the acupuncture and moxibustion Department. On the basis of the conventional care in the control group, the observation group were treated with family empowerment model intervention for 14 days and was followed up for 28 days. Primary caregivers′ swallowing care ability, Caregiver Preparedness Scale (CPS), patients′ swallowing function rate, Swallowing Related Quality of Life (SWALQOL) were used to evaluate the effects before intervention and at the end of intervention.Results:There were 18 males and 19 females primary caregivers in the control group, aged (55.61 ± 7.43) years old. There were 18 males and 21 females primary caregivers in the observation group, aged (58.23 ± 8.22) years old. The swallowing care ability score showed a statistically significant difference between the observation group (143.47 ± 3.96) and the control group (107.74 ± 1.43) ( t=-26.76, P<0.05). After intervention, the caregiver preparedness scale was (26.11 ± 3.81) in the observation group, and (18.35 ± 4.54) in the control group, and the difference was statistically significant ( t=-4.11, P<0.05).The patients′ swallowing function rate and SWALQOL score were respectively 97.44% (38/39) and (91.41 ± 8.08) points in the observation group, and 72.97% (27/37) and (80.33 ± 4.21) points in the control group, and the difference was both statistically significant ( χ2=10.76, t=-2.54, both P<0.05). Conclusions:The implementation of family empowerment model could enhance the swallowing care ability and care preparedness of primary caregivers of the first-episode stroke dysphagia patients, which could further improve patients′ swallowing function and life quality.