Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Alzheimer′s disease (AD) is a neurodegenerative disorder. In the past few decades, the exact mechanisms underlying the onset of the disease have remained unclear, and treatment options are still lacking. Due to the inability of two-dimensional cell and animal models to fully simulate the pathogenesis of AD, there have been shortcomings in clinical trials of new drugs. The development of organoids and organ-on-a-chip technologies has improved the dilemma of AD research, providing reliable in vitro research models for studying pathogenic mechanisms and drug screening. This article elaborates on the applications and progress of organoids and organ-on-a-chip in AD modeling, pathogenesis, and drug development, and discusses the current limitations of organoids and organ-on-a-chip and their future perspectives.

Microcephaly is a common pediatric neurodevelopmental disorder with complex etiology. In recent years, with the development of brain organoid technology, there has been rapid progress in understanding the pathogenesis and treatment strategies of microcephaly using this technology. This article elucidates the advantages of brain organoids over traditional experimental models, reviews the research progress of brain organoid technology in disease modeling and drug screening for various causes of microcephaly, and discusses the limitations and future prospects of brain organoids.

Objective To observe the expression of ciz1 in human colorectal cancer tissues and analyse the relationship between their expression and clinicopathologic features.Methods We detected the expression of Ciz1 and Ciz1 mRNA by immunohistochemistry and Western blotting.The relationship between the expression of ciz1 and clinicopathologic features was analied.Results According to immunohistochemical results,Ciz1 showed significant high expression in the primary lesion of colorectal cancer tissue,compared to normal adjacent tissues(66.7%vs.35.0%,P=0.001).Through Western blot analysis,it was found that the relative expression level in colorectal cancer tissue was 0.32±0.03,while in normal colorectal mucosal tissue it was 0.11±0.01.In addition,the relative expression level of Ciz1 in colorectal cancer tissue was significantly higher than that in normal intestinal mucosal tissue(P<0.05).The study found that the overexpression of Ciz1 in colorectal cancer tissue is significantly correlated with the T stage(P=0.018),lymph node metastasis(P=0.022),and AJCC stage(P=0.017)of the cancer.The age,gender,tumor location,degree of differentiation,and the presence of distant metastasis of patients were not correlated with this(P>0.05).The expression level of Ciz1 in colorectal cancer tissue is significantly increased,which is closely related to the T stage(P=0.018),lymph node metastasis(P=0.022),and American Joint Committee on Cancer stage(P=0.017)of colorectal cancer.Conclusion This association suggests that Ciz1 may play an important role in tumor staging,participating in the development and spread of tumors.Therefore,it can be foreseen that Ciz1 is expected to become a new biomarker for evaluating the prognosis of colorectal cancer patients.

OBJECTIVE: To explore the biomarkers of tinnitus in vestibular schwannoma patients using electroencephalographic (EEG) microstate technology. METHODS: The EEG and clinical data of 41 patients with vestibular schwannoma were collected. All the patients were evaluated by SAS, SDS, THI and VAS scales. The EEG acquisition time was 10-15 min, and the EEG data were preprocessed and analyzed using MATLAB and EEGLAB software package. RESULTS: Of the 41 patients with vestibular schwannoma, 29 patients had tinnitus and 12 did not have tinnitus, and their clinical parameters were comparable. The average global explanation variances of the non-tinnitus and tinnitus groups were 78.8% and 80.1%, respectively. The results of EEG microstate analysis showed that compared with those without tinnitus, the patients with tinnitus had an increased frequency (P=0.033) and contribution (P=0.028) of microstate C. Correlation analysis showed that THI scale scores of the patients were negatively correlated with the duration of microstate A (R=-0.435, P=0.018) and positively with the frequencies of microstate B (R=0.456, P=0.013) and microstate C (R=0.412, P=0.026). Syntax analysis showed that the probability of transition from microstate C to microstate B increased significantly in vestibular schwannoma patients with tinnitus (P=0.031). CONCLUSION EEG microstate features differ significantly between vestibular schwannoma patients with and without tinnitus. This abnormality in patients with tinnitus may reflect the potential abnormality in the allocation of neural resources and the transition of brain functional activity.
Humans ; Neuroma, Acoustic/complications* ; Electroencephalography ; Patients ; Probability

Objective:To rapidly evaluate the level of healthcare resource demand for laboratory testing and prevention and control of corona virus disease 2019 (COVID-19) in different epidemic situation, and prepare for the capacity planning, stockpile distribution, and funding raising for infectious disease epidemic response.Methods:An susceptible, exposed, infectious, removed infectious disease dynamics model with confirmed asymptomatic infection cases and symptomatic hospitalized patients was introduced to simulate different COVID-19 epidemic situation and predict the numbers of hospitalized or isolated patients, and based on the current COVID-19 prevention and control measures in China, the demands of resources for laboratory testing and prevention and control of COVID-19 were evaluated.Results:When community or local transmission or outbreaks occur and total population nucleic acid testing is implemented, the need for human resources is 3.3-89.1 times higher than the reserved, and the current resources of medical personal protective equipment and instruments can meet the need. The surge in asymptomatic infections can also increase the human resource demand for laboratory testing and pose challenge to the prevention and control of the disease. When vaccine protection coverage reach ≥50%, appropriate adjustment of the prevention and control measures can reduce the need for laboratory and human resources.Conclusions:There is a great need in our country to reserve the human resources for laboratory testing and disease prevention and control for the response of the possible epidemic of COVID-19. Challenges to human resources resulted from total population nucleic acid testing and its necessity need to be considered. Conducting non-pharmaceutical interventions and encouraging more people to be vaccinated can mitigate the shock on healthcare resource demand in COVID-19 prevention and control.

Objective To study the influence of foot progression angle on tibial shock during running. Methods The normal, toe-in and toe-out gait of fifteen healthy adults was tested during running trials on a treadmill. The differences in tibial shock (impact peak, average loading rate, instantaneous loading rate and maximum tibia acceleration) for runners at different foot progression angles were analyzed to explore the influence of foot progression angle on tibial shock. The changes in sagittal plane trunk angle, strike pattern, stride frequency and step width of runners under three gaits were also compared to explore its possible causes. Results Compared with normal gait, the maximum tibial acceleration of toe-in and toe-out gait was increased by 19.3% and 24.5%, impact peak was increased by 7.6%, average loading rate was increased by 7.9% and 9.5%, instantaneous loading rate was increased by 3.9% and 10-.9%, with significant statistic differences. No significant changes were found in sagittal plane trunk angle, strike pattern, stride frequency and step width. Conclusions Foot progression angle might be an another gait parameter which affected tibial shock during running in addition to other related known gait parameters such as sagittal plane trunk angle, strike pattern, stride frequency and step width，which would provide an important reference for prevention of tibial stress fracture.

Objective To explore the effects of different degrees of intermittent hypoxia (IH) on the activation and the secretion of extracellular matrix in MLg lung fibroblast cell line. Methods MLg lung fibroblast cells in logarithmic growth phase were exposed for 5%O2 for 100 seconds and 21%O2 for 120 seconds in 1 h, 4 h and 8 h groups (IH1, IH4 and IH8) and normoxia group (21%O2 for 8 h, N group). The cells in each group were collected at the end of experiment. Real-time PCR was used to measure the mRNA expression levels ofα-SMA and typeⅠcollagen (COL1) A1, and Western blot assay was used to detect the protein expression levels ofα-SMA and COL1. Results The mRNA and protein expression levels ofα-SMA and COL1 were significantly increased in IH1, IH4 and IH8 groups than those in N group (all P < 0.05). Furthermore, expression levels of α-SMA and COL1 showed a time-dependent increase with IH exposure time. Conclusion The intermittent hypoxia can promote the cell activation and the extracellular matrix secretion of mouse lung fibroblast cells, which may be related with the oxidative stress.

Objective To explore the effects of cobalt chloride (CoCl2)-induced hypoxia on migration of melanoma cells, and to detect the transcription, expression and secretion of Follistatin-like 1(FSTL1) in this process. Methods B16F10 melanoma cell line was treated with CoCl2 in order to mimic hypoxia. Experimental cells were divided into three groups: 0μmol/L, 50μmol/L and 100μmol/L CoCl2 treatment groups. MTT assay was used to assure cell viability, and to determine the treatment concentration of CoCl2. Transwell assay was used to determine the migration ability of B16F10 melanoma cell line. Real-time PCR was used to measure the mRNA expression of Fstl1. Western blot assay was used to detect the intracel?lular and extracellular protein expression of FSTL1. Results The cell viability of B16F10 melanoma cell line was signifi?cantly reduced by CoCl2 treatment, with a time and concentration-dependent manner. The migration ability of B16F10 cell line was significantly increased in CoCl2 treated group compared with that of control group (P<0.05). The mRNA level of Fstl1 was obviously higher in CoCl2 treated group than that of control group (P<0.05). The intracellular expression of FSTL1 protein was consistent with the expression trend of Fstl1 mRNA. Simultaneously, the extracellular protein level of FSTL1 was significantly decreased compared with that of control group. There was no expression of FSTL1 in 100μmol/L CoCl2 treat?ment group. Conclusion The migration ability of melanoma cell line is enhanced by CoCl2 treatment, which may be associ?ated with expression and secretion of FSTL1, however, the relevant mechanism still needs further investigation.

Objective To explore the effect of obstructive sleep apnea syndrome (OSAS), OSAS-like intermittent hypoxia (IH)on the expression levels of P-YAP and YAP in A549 lung cancer cell lines. Methods A549 cells were treated with IH exposure ( exposed to 5%O2 for 300 seconds and 21%O2 for 300 seconds) for 1, 3 and 6 h (IH1, IH3, IH6) or normoxia exposure (N group). Quantificational real-time PCR was used to measure the mRNA expression levels of YAP. Western blot assay was used to detect the protein expression levels of YAP and P-YAP. Results The mRNA expression levels of YAP were significantly increased with the increase of IH exposure time points in IH1 (2.50±0.18), IH3 (4.07±0.25) and IH6 (9.18 ± 0.58) groups than those in N group (1.00 ± 0.01) (all P<0.05). The protein expression levels of YAP were significantly increased with the increase of IH exposure time points in IH1, IH3 and IH6 groups than those in N group. The protein expression levels of P-YAP were significantly decreased with the increase of IH exposure time points in IH 1, IH3 and IH6 groups than those in N group. Conclusion YAP cell signaling plays an important role in the process of OSAS-like IH induced tumor development.