Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Odds ratio (OR) and relative risk (RR) are the most commonly used statistical indicators for the estimation of the association between exposure and outcome. In the cohort study with rare outcomes, the estimated OR approximately equals RR, but RR seems more interpretable. The study aims to explore the difference between OR and RR estimated by different multivariate analyses to provide reference for the selection of more appropriate multivariate regression methods and reporting indicators for estimating the association between exposure and rare outcome in cohort studies. This case study used the data from China birth cohort study. Modes of conception and congenital disabilities were regarded as exposure and outcome, respectively. Maternal age, family history of congenital disabilities with clear evidence were included as covariates. Logistic regression, log-binomial regression, and Poisson regression were used to estimate the OR and RR, respectively. Then, OR, RR, and their 95%CI estimated by three regression models were compared. The OR estimated by logistic regression was approximately equal to the RR estimated by log-binomial regression or Poisson regression. However, the RR estimated by log-binomial regression or Poisson regression was closer to 1.00, with a narrower 95%CI. Log-binomial regression or Poisson regression might have non convergence or over dispersion problems. It is recommended to report the RR obtained by log-binomial regression or Poisson regression in the cohort study with rare outcomes if applicable.

The treatment ideas with acupuncture for knee osteoarthritis (KOA) are explored on the base of Dongyuan needling technology. Regarding the rules of acupoint selection, Zusanli (ST 36) is predominant, the back-shu points are used for the disorders related to the invasion of exogenous factors, and the front-mu points are for the cases caused by internal injury. Besides, the xing-spring points and shu-stream points are preferred. In treatment of KOA, besides the local points, the front-mu points, i.e. Zhongwan (CV 12), Tianshu (ST 25) and Guanyuan (CV 4), are selected specially to tonifying the spleen and stomach. The earth points and acupoints on the earth meridians (i.e. Yinlingquan [SP 9], Xuehai [SP 10], Liangqiu [ST 34], Dubi [ST 35], Zusanli [ST 36] and Yanglingquan [GB 34]) are optional to coordinate yin and yang, essence and qi , and regulate the qi movement of spleen and stomach. The shu-stream points of liver, spleen and kidney meridians (Taichong [LR 3], Taibai [SP 3] and Taixi [KI 3]) are chosen to promote meridian circulation and regulate zangfu functions.
Humans ; Osteoarthritis, Knee ; Acupuncture Therapy ; Meridians ; Acupuncture Points ; Spleen

The quality markers(Q-markers) of Shujin Huoxue Capsules were comprehensively discriminated based on the five principles of transfer and traceability, specificity, compatibility, effectiveness and measurability. The compounds that could be transferred from the original medicinal materials to the preparation were selected with the principle of transfer and traceability. The specific components in the prescription were screened by reviewing literature with the principle of specificity. According to the principle of compatibility, the attributes of compounds were evaluated by the sovereign, minister, assistant and guide combination rules of the original medicinal materials in the prescription. According to the principle of measurability, the measurable components were summarized by reference to the pharmacopoeia and literature combined with the content. The mechanism of Shujin Huoxue Capsules in the treatment of osteoporosis was studied through network pharmacology based on the principle of effectiveness, which was the evaluation index of effectiveness. The chemical components screened out above were regarded as candidate Q-markers, and the cobweb model was plotted to obtain the comprehensive score of Q-markers. Hydroxysafflor yellow A, trachelosid, eleutheroside B, α-cyperone, protocatechuic acid, protocatechualdehyde and 4-methoxy salicylaldehyde were discriminated as the Q-markers of Shujin Huoxue Capsules based on the five principles combined with cobweb model.
Biomarkers ; Capsules ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis. METHODS: The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses. RESULTS: Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1. CONCLUSION The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.
Animals ; China ; Cysteine-Rich Protein 61/metabolism* ; Disease Models, Animal ; Drugs, Chinese Herbal/therapeutic use* ; Imiquimod/adverse effects* ; Inflammation/drug therapy* ; Intercellular Adhesion Molecule-1/genetics* ; Interferon-gamma ; Mice ; Mice, Inbred BALB C ; Psoriasis/pathology* ; RNA, Messenger/therapeutic use*

AIM: To explore the clinical efficacy of the myopic with moderate to high astigmatism correction between corneal topography-guided femtosecond laser in situ keratomileusis(FS-LAISK)and Toric implantable collamer lens(TICL).METHODS: A total of 60 patients(115 eyes)with moderate to high astigmatism in myopia(115 eyes)from June 2019 to June 2021 and treated in the refractive center of Heyuan Aier Eye Hospital were enrolled in the study, then were divided into Group A and Group B according to the operations they would accept. There were 32 patients(62 eyes)in the Group A treated with corneal topography-guided FS-LASIK and 28 patients(53 eyes)in the Group B treated with TICL implantation. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical diopter and residual astigmatism were recorded preoperatively and postoperatively at 3mo, surgical safety and efficacy were evaluated, and the Alpins vector analysis was used to evaluate the astigmatism.RESULTS: The postoperative at 3mo, there were no differences in the safety index(1.163±0.167 vs 1.136±0.194)and the efficacy index(1.145±0.159 vs 1.123±0.196)between the patients of the two groups(P>0.05). However, the astigmatism vector analysis showed that there were statistically differences in the index of success index [0.125(0.091, 0.200)vs 0.200(0.167, 0.250)], the correction index [1.000(0.902, 1.066)vs 0.834(0.783, 0.869)] and the flattening index [1.000(0.922, 1.079)vs 0.835(0.795, 0.870)](P<0.01).CONCLUSION:Corneal topography-guided FS-LASIK and TICL implantation were effective and safe in correcting myopia with moderate to high astigmatism, and corneal topography-guided FS-LASIK perform better than TICL implantation for the astigmatism correction.

Objective: To establish a three-dimensional model of middle ear-eustachian tube based on Chinese digital visual human dataset, and the deformation and pressure changes of the middle ear-eustachian tube system after eustachian tube opening are simulated by computer numerical simulation. Methods: The first female Chinese Digital Visual Human data was adopted. The images were imported by Amira image processing software, and the images were segmented by Geomagic software to form a three-dimensional model of middle ear-eustachian tube system, including eustachian tube, tympanum, tympanic membrane, auditory ossicles, and mastoid air cells system. The 3D model was imported into Hypermesh software for meshing and analysis. The structural mechanics calculation was carried out by Abaqus, and gas flow was simulated by Xflow. The tissue deformation and middle ear pressure changes during eustachian tube opening were numerically simulated by fluid-solid coupling algorithm. Several pressure monitoring points including tympanum, mastoid, tympanic isthmus, and external auditory canal were set up in the model, and the pressure changes of each monitoring point were recorded and compared. Results: In this study, a three-dimensional model of middle ear-eustachian tube and a numerical simulation model of middle ear ventilation were established, including eustachian tube, tympanum, mastoid air cells, tympanic membrane, and auditory ossicles. The dynamic changes of the model after ventilation could be divided into five stages according to the pressure. In addition, the pressure changes of tympanum and tympanic isthmus were basically synchronous, and the pressure changes of mastoid air cells system were later than that of tympanum and tympanic isthmus, which verified the pressure buffering effect of mastoid. The extracted pressure curve of the external auditory canal was basically consistent with that of tympanometry in terms of value and trend, which verified the effectiveness of the model. Conclusions: The numerical simulation model of middle ear-eustachian tube ventilation established in this paper can simulate the tissue deformation and middle ear pressure changes after eustachian tube opening, and its accuracy and effectiveness are also verified. This not only lays a foundation for further research, but also provides a new research method for the study of middle ear ventilation.
China ; Ear, Middle ; Eustachian Tube ; Female ; Human Body ; Humans ; Middle Ear Ventilation

Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D₃ (VitD₃) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD₃, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11β-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD₃, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.
Rats ; Animals ; Glucocorticoids/metabolism* ; Rats, Sprague-Dawley ; Nicotine/metabolism* ; Hydrocortisone/metabolism* ; Muscle, Smooth, Vascular ; Dexamethasone/metabolism* ; Vascular Calcification/metabolism* ; Myocytes, Smooth Muscle/metabolism* ; Cells, Cultured

OBJECTIVES: To study the genetic polymorphism and population genetic parameters of 16 X-STR loci in Xinjiang Uygur population. METHODS: The Goldeneye^® DNA identification system 17X was used to amplify 16 X-STR loci in 502 unrelated individuals (251 females and 251 males). The amplified products were detected by 3130xl genetic analyzer. Allele frequencies and population genetic parameters were analyzed statistically. The genetic distances between Uygur and other 8 populations were calculated. Multidimensional scaling and phylogenetic tree were constructed based on genetic distance. RESULTS: In the 16 X-STR loci, a total of 67 alleles were detected in 502 Xinjiang Uygur unrelated individuals. The allele frequencies ranged from 0.001 3 to 0.572 4. PIC ranged from 0.568 8 to 0.855 3. The cumulative discrimination power in females and males were 0.999 999 999 999 999 and 0.999 999 999 743 071, respectively. The cumulative mean paternity exclusion chance in trios and in duos were 0.999 999 997 791 859 and 0.999 998 989 000 730, respectively. The genetic distance between Uygur population and Kazakh population was closer, and the genetic distance between Uygur and Han population was farther. CONCLUSIONS The 16 X-STR loci are highly polymorphic and suitable for identification in Uygur population, which can provide a powerful supplement for the study of individual identification, paternity identification and population genetics.
Female ; Humans ; Male ; DNA, Ribosomal ; Ethnicity/genetics* ; Gene Frequency ; Paternity ; Phylogeny ; Polymorphism, Genetic ; Microsatellite Repeats ; Chromosomes, Human, X/genetics*