1.The Role and Mechanism of Circadian Rhythm Regulation in Skin Tissue Regeneration
Ya-Qi ZHAO ; Lin-Lin ZHANG ; Xiao-Meng MA ; Zhen-Kai JIN ; Kun LI ; Min WANG
Progress in Biochemistry and Biophysics 2025;52(5):1165-1178
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.
2.Role and mechanism of RASAL1 in increase of pulmonary vascular endothelial permeability induced by homocysteine
Xin-Yi LI ; Kai-Yue QIN ; Zi-Yao YANG ; Ling ZHANG ; Zhen LI ; Ya-Li YANG ; Xi XU ; Xiao-Ling YANG
Chinese Pharmacological Bulletin 2024;40(8):1454-1461
Aim To investigate the effect of homocys-teine(Hcy)on the permeability of pulmonary micro-vascular endothelial cells(PMVECs)and the role and mechanism of RASAL1.Methods CBS+/-mice were fed a high methionine diet(HMD)for 16 weeks to replicate an animal model of hyperhomocysteinemia(HHcy).HE staining was used to observe the changes in lung tissue structure.qRT-PCR was used to detect the levels of RASAL1 and DNMT1 mRNA in lung tis-sue.Western blot was used to detect the expression of RASAL1,DNMT1,ZO-1,and VE cadherin proteins.Methylation specific PCR was used to detect methyla-tion in the RASAL1 promoter region.PMVECs were transfected with Ad-RASAL1 to detect the expression of ZO-1 and VE cadherin.The si-DNMT1 interference fragment was transfected into PMVECs,and the ex-pression of the RASAL1 was detected by qRT-PCR and Western blot.Results Serum Hcy level of HMD mice was significantly raised,and HE staining showed severe structural disorder in lung tissue.The expres-sion of RASAL1,ZO-1,and VE cadherin was de-creased,while the expression of DNMT1 was in-creased.The degree of methylation in the RASAL1 promoter region was raised.The expression of ZO-1 and VE cadherin increased after PMVECs were trans-fected with Ad-RASAL1.After knocking down DN-MT1,RASAL1 expression was increased.Conclusion Hcy can increase the permeability of PMVECs,and its mechanism is related to the upregulation of RASAL1 methylation level.
3.Clinical analysis of uterine artery embolization combined with ultrasound-guided curettage in treatment of caesarean scar pregnancy
Wen-Zhen WANG ; Ling-Yun WEI ; Ya-Ling WEN ; Xiao-Chun LIU
Journal of Regional Anatomy and Operative Surgery 2024;33(8):689-692
Objective To evaluate the efficacy of uterine artery embolization(UAE)combined with ultrasound-guided curettage in the treatment of type Ⅱ and type Ⅲ caesarean scar pregnancy(CSP).Methods The clinical data of 90 patient with CSP in our hospital were analyzed retrospectively,the patients were divided into type Ⅱ group and type Ⅲ group according to preoperative vaginal color Doppler ultrasound.Patients in both groups were treated with UAE combined with ultrasound-guided curettage.The intraoperative and postoperative conditions of patients between the two groups were compared and analyzed.Results The cure rate of type Ⅱ group(92.5%)was higher than that of type Ⅲ group(65.2%),the intraoperative blood loss,time of postoperative serum β-hCG turned negative,postoperative mass disappearance time of patients in type Ⅱ group were less/shorter than those in type Ⅲ group,the differences were statistically significant(P<0.05);there was no statistical difference in length of hospitalization or time to menstruation recovery of patients between the two groups(P>0.05).Conclusion UAE combined with ultrasound-guided curettage is ideal for patients with type Ⅱ CSP at 8 to 10 weeks of gestation,and can be used as a recommended treatment.However,the cure rate of this method for type Ⅲ CSP is low,the comprehensive choice should be considered,including the specific situation of the patient and the local medical level.
4.In Vitro Amplification of NK Cells from Feeder Layer Cells Expressing IL-21
Zhen-Zhao XU ; Xue-Hua ZHANG ; Ling-Ping ZHAO ; Gao-Hua LI ; Tian-Tian CUI ; Xiao-Ling WANG ; Xuan LI ; Ru-Ge ZANG ; Wen YUE ; Ya-Nan WANG ; Guo-Xin LI ; Jia-Fei XI
Journal of Experimental Hematology 2024;32(5):1578-1584
Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P<0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.
5.The role of vortex veins in the pathogenesis of central serous chorioretinopathy
Bei XIAO ; Yanping SONG ; Ming YAN ; Ya YE ; Zhen HUANG
Chinese Journal of Ocular Fundus Diseases 2024;40(4):319-323
Central serous chorioretinopathy (CSC) is one of the main causes of impaired visual function in middle-aged men. CSC is characterized by a thickening of the choroid and hyperpermeability of the choroidal vessels, resulting in serous subretinal fluid. The pathogenesis of CSC is not fully understood. Since the introduction of indocyanine green angiography, the detection of the influence of the vortex veins in CSC, it has been established that the presence of a thick choroid may be caused by congestion of the vortex vein, resulting in new choroidal drainage through a vortex vein anastomosis. The study of vortex venous blood hemodynamics has elucidated the new concept of the pathogenesis of CSC, deepened our understanding of the disease, and provided a theoretical basis for new treatment methods. With a better understanding of the pathogenesis of CSC, we expect to be able to stratify patients at risk in the clinic and evaluate optimized treatment options for patients with CSC
6.Association between vortex vein dilatation patterns and choroidal thickness changes in patients with central serous chorioretinopathy
Bei XIAO ; Yanping SONG ; Ya YE ; Zhen HUANG ; Ming YAN
Chinese Journal of Ocular Fundus Diseases 2024;40(5):360-365
Objective:To observe the changes of chorioidal thickness (ChT) in patients with central serous chorioretinopathy (CSC) in different mode of vortic venous dilation.Methods:A prospective cross-sectional observational study. A total of 80 patients with 89 eyes (CSC group) diagnosed in Department of Ophthalmology, General Hospital of Central Theater Command from April to October 2023 were included in the study. Among them, 64 males had 71 eyes and 17 females had 18 eyes. A total of 15 healthy volunteers matched in age and sex were selected as the control group. Among them, 14 men had 26 eyes and one woman had two eyes. The macular region was examined by ultra-wide-angle scanning frequency source optical coherence tomography (OCTA) with BM400K BMizar made by TowardPi (Beijing) Medical Technology Co., LTD. Scanning rate 1 536 A scanning×1 280 B scanning, scanning range 24 mm×20 mm. The accompanying software delineated nine subfields (superotemporal, upper, superonasal, temporal, central, nasal, inferotemporal, lower, inferonasal regions) to record ChT. En-face OCTA mode was utilized to observe the anatomy and functional anastomosis of the vortex veins above and below the choroidal blood layer. Eyes in the CSC group were further categorized into upper-dominant, symmetrical, and lower-dominant groups based on the difference in vortex vein expansion shown in the choroidal layer of the en-face image, with 36, 35, and 18 eyes respectively. Statistical analysis included the use of independent samples t-test or Mann-Whitney test for comparison between two groups, one-way analysis of variance or Kruskal-Wallis H test for comparison between multiple groups, and the χ test or Fisher test for categorical variables. Results:Compared with the control group, ChT in the CSC group was thickened in the foveal area and different areas of the macula, with the greatest difference in the fovea, and the differences were statistically significant ( t=3.345, 5.018, 2.902, 4.667, 7.276, 3.307, 3.868, 4.795, 2.583; P<0.05). Compared with the ChT of the control group, there was no statistically significant difference in the superotemporal, region of the upper-dominant group ( t=1.510, P>0.05); in other regions, the differences were statistically significant ( t=3.207, 5.163, 2.526, 4.310, 6.285, 2.656, 3.812, 2.173; P<0.05). The differences in the foveal area and other areas in the symmetrical group were statistically significant ( t=4.488, 5.554, 3.457, 5.314, 7.256, 3.507, 5.584, 6.019, 2.994; P<0.05). In the superotemporal, and superonasal, regions of the lower dominant group, the differences were not statistically significant ( t=1.150, 1.465; P<0.05); in other regions, the differences were statistically significant ( t=2.278, 4.168, 5.244, 2.783, 5.040, 3.432, 2.095; P<0.05). Conclusion:The dilated distribution of vortex veins on en-face ultra-wide-angle OCTA has a corresponding relationship with ChT. In eyes with CSC, the superior vortex vein drainage system may be the primary route for choroidal drainage.
7.A comparative study of choroidal parameters in contralateral eyes of patients with pachychoroid neovasculopathy and central serous chorioretinopathy
Bei XIAO ; Yanping SONG ; Ming YAN ; Ya YE ; Zhen HUANG
Recent Advances in Ophthalmology 2024;44(5):376-381
Objective To compare choroidal parameters and morphological changes in asymptomatic contralateral eyes of patients with pachychoroid neovasculopathy(PNV)and central serous chorioretinopathy(CSC)using ultra-wide-field swept-source optical coherence tomography angiography(UWF SS-OCTA).Methods A prospective,cross-section-al,observational study was conducted,including 23 asymptomatic contralateral eyes of 23 CSC patients and 19 asympto-matic contralateral eyes of 19 PNV patients treated in our Ophthalmology Department from April 2023 to September 2023,as well as 22 eyes of 22 age-and sex-matched healthy individuals.These eyes were divided into the CSC contralateral eye group,PNV contralateral eye group,and healthy eye group,respectively.There was no statistically significant difference in age,male ratio,and best corrected visual acuity among the three groups(all P>0.05).All subjects underwent UWF SS-OCTA imaging examination and comparison,and their choroidal thickness(CT),vascular density(VD)in the major vas-cular layer of the choroid(ratio of blood flow pixel area to total area of the target area),and choroidal vascular index(CVI)(ratio of choroidal vascular lumen volume to total volume of choroidal vessels and stromata)in 9 zones(superior temporal,superior,superior nasal,temporal,foveal,nasal,inferior temporal,inferior,and inferior nasal)were measured and recorded,respectively.The macular subfoveal retinal thickness,subfoveal choroidal thickness(SFCT),and asymmet-ric dilation and anastomosis of the vortex veins were examined and compared in each group of patients.Results There was a statistically significant difference in macular SFCT among the three groups(all P<0.01).There was a statistically significant difference in the proportion of asymmetric dilation or anastomosis of the vortex veins among the three groups(all P<0.001).The CVI in the superior nasal and nasal zones in the CSC contralateral eye group were higher than those in the PNV contralateral eye group(both P<0.05).The CVI and average CVI in the superior nasal,temporal,foveal,inferi-or,and inferior nasal zones in the CSC contralateral eye group were higher than those in the healthy eye group(all P<0.05).The CVI in the temporal,foveal,and inferior zones in the PNV contralateral eye group were higher than those in the healthy eye group(all P<0.05).The VD in the major vascular layer of the choroid in the superior temporal,superior,su-perior nasal,foveal,and inferior temporal zones in the CSC contralateral eye group were lower than those in the healthy eye group(all P<0.05).The VD in the major vascular layer of the choroid in the PNV contralateral eye group were lower than that in the healthy eye group in all zones(all P<0.001).The CT in the superior temporal and superior nasal zones in the CSC contralateral eye group were higher than those in the PNV contralateral eye group(both P<0.05).The CT in the superior temporal,superior,superior nasal,temporal,foveal,inferior,and inferior nasal zones in the CSC contralateral eye group were higher than those in the healthy eye group(all P<0.05).The CT in the superior,temporal,foveal,and in-ferior zones in the PNV contralateral eye group were higher than those in the healthy eye group(all P<0.05).Conclu-sion This study provides validation from the perspective of the fellow eye that CSC and PNV may not be different stages of the same disease.CSC and PNV are not unilateral diseases,but bilateral choroida diseases that manifest in one eye.
8.Observation on the efficacy of subthreshold micropulse laser photocoagula-tion in the treatment of central serous chorioretinopathy based on multimodal imaging classification
Bei XIAO ; Yanping SONG ; Ming YAN ; Ya YE ; Zhen HUANG ; Cong CHEN ; Yumeng DENG
Recent Advances in Ophthalmology 2024;44(7):531-535
Objective To observe the efficacy of 577 nm subthreshold micropulse laser photocoagulation(SMLP)on central serous chorioretinopathy(CSC)and explore the baseline characteristics and prognostic features of multimodal ima-ging-based CSC.Methods A retrospective analysis was conducted on 44 patients(46 eyes)with CSC diagnosed at the Ophthalmology Department of the General Hospital of Central Theater Command,PLA from June 2017 to May 2022.The pa-tients were classified into the simple CSC group(23 eyes)and the complex CSC group(23 eyes)based on the multimodal imaging classification.All patients underwent 577 nm SMLP treatment.The best corrected visual acuity(BCVA)and cen-tral macular thickness(CMT)of patients between the two groups were compared before treatment and at 1,3 and 6 months after treatment.The intra-group and inter-group changes and the complete absorption rate of subretinal fluid(SRF)in CSC eyes of patients between the two groups were assessed before treatment and at 6 months after follow-up.Results The BCVA of patients in the simple CSC group significantly improved at 6 months after treatment compared with the base-line(P=0.010);the BCVA of patients in the complex CSC group significantly improved at 3 and 6 months after treatment compared with the baseline(both P<0.01).The CMT of patients in the simple CSC group was significantly lower than the baseline at 1,3,and 6 months after treatment(all P<0.05);the CMT of patients in the complex CSC group was signifi-cantly lower than the baseline at 1 and 6 months after treatment(both P<0.05);the change in CMT from baseline after 6 months of treatment for simple CSC was(-163.74±88.10)μm,the change in CMT from baseline after 6 months of treat-ment for complex CSC was(-71.96±164.30)μm,and the difference between the two groups was statistically significant(P=0.023).During the follow-up period,the number of eyes with persistent SRF in the simple CSC group was significant-ly lower than that in the complex CSC group(P<0.05).The complete absorption rate of SRF at 6 months after treatment in the simple CSC group was greater than that in the complex CSC group(P<0.05).Conclusion The prognosis of sim-ple CSC treated with 577 nm SMLP is better than that of complex CSC,and the new multimodal imaging classification has a certain value in predicting the prognosis of CSC after SMLP.
9.Research progress of fluorescent probes in uric acid detection
Di-Di XING ; Ruo-Jin LIU ; Jia-Yu QI ; Ning MA ; Ya-Kun JI ; Jia-Xin ZHOU ; Yu-Shan XING ; Xiao-Lan ZHEN
Chinese Medical Equipment Journal 2024;45(6):93-104
The advantages of fluorescence detection of uric acid were introduced compared to the traditional detection methods.The preparation process,detection principle and performance of organic,inorganic and organic-inorganic hybrid fluorescent probes were reviewed.The advantages and disadvantages of kinds of fluorescent probes were analyzed when used for uric acid detection,and the futural directions were pointed out for related research.[Chinese Medical Equipment Journal,2024,45(6):93-104]
10.Imaging characteristics of the affected eye and fellow eye in patients with central serous chorioretinopathy of different ages
Bei XIAO ; Yanping SONG ; Ya YE ; Zhen HUANG ; Ming YAN
International Eye Science 2024;24(6):937-942
AIM: To observe the imaging characteristics of the affected eyes of patients with central serous chorioretinopathy(CSC)of different ages and their asymptomatic fellow eyes.METHODS: Retrospective study. A total of 76 cases(88 eyes)of CSC patients diagnosed in the ophthalmology department of our hospital from April to September, 2023 and 35 cases(35 eyes of asymptomatic fellow eyes of patients with unilateral CSC)were selected for the study. According to age, they were divided into young and middle-aged groups(<40 years old), middle-aged groups(40-50 years old)and middle-aged and elderly groups(>50 years old). The imaging features of the affected eyes of CSC patients of different ages and their asymptomatic fellow eyes were observed.RESULTS: The subfoveal choroidal thickness(SFCT)of CSC eyes in the young and middle-aged patients(487.30±83.33 μm)was significantly greater than that of the middle-aged group(414.17±96.02 μm, P<0.05)and the middle-aged and elderly group(409.4±107.42 μm, P<0.05). The incidence of choroidal neovascularization(CNV)in CSC patients of the middle-aged and elderly group was significantly higher than that in the young and middle-aged group(P<0.0167). The SFCT of the asymptomatic fellow eye of the unilateral CSC patient in the young and middle-aged group(511.29±40.89 μm)was significantly larger than that of the middle-aged and elderly group(364.76±82.26 μm, P<0.05). Among them, the vortex vein anastomosis rate in eyes with CSC is higher than 90%, and vortex vein anastomosis or dilatation is present in all asymptomatic fellow eyes of CSC patients.CONCLUSION: There are differences in the imaging manifestations of CSC-affected eyes and their asymptomatic fellow eyes of different age groups. SFCT is generally thickened and gradually becomes thinner with the growth of age. The incidence of CNV in CSC-affected eyes is the highest in the middle-aged and elderly group. In addition, vortex vein anastomosis and dilatation are common in CSC-affected eyes and asymptomatic fellow eyes.

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