OBJECTIVETo investigate the short-term prognostic value of the indocyanine green clearance test when used in combination with the model for end-stage liver disease (MELD) scoring system to assess patients with hepatitis B virus acute-on-chronic liver failure (HBV-ACLF).

METHODSClinical data of 105 patients diagnosed with HBV-ACLF were retrospectively analyzed. The indocyanine green retention rate at 15 minutes (ICGR15), clinical data within 24 h after diagnosis, Child-Turcotte-Pugh (CTP) classification, MELD score, MELD combined with sodium concentration (MELD-Na) score, and King's Hospital (KCH) criteria data were collected for analysis. Measurement data were assessed by t-test and count data by the chi-square test. Short-term predictive accuracy for patients with HBV-ACLF was compared between different models using the area under the receiver operating characteristic (ROC) curve (AUC).

RESULTSThe mortality rate for all patients was 45.71%. Comparison of the survivors versus the non-survivors showed that age, total bilirubin, albumin, cholinesterase, creatinine, international normalized ratio, and incidence positive rate of relative complications (hepatorenal syndrome, hepatic encephalopathy) were significantly different between the two groups (all, P less than 0.05). The ICGR15 was found to be positively correlated with MELD score (r = 0.205, P less than 0.05). The MELD-ICGR15 model constructed by logistic regression analysis was: Logit(P) = 0.193 * MELD + 0.130 * ICGR15 - 11.256. The AUC was 0.880 and the cut-off was -0.706, with 89.6% sensitivity and 75.4% specificity. The AUC of the MELD-ICGR15 model was significantly higher than that of the ICGR15 (0.820), MELD score (0.779), MELD-Na score (0.761), KCH criteria (0.680), and CTP classification (0.631) (all, P less than 0.05).

CONCLUSIONICGR15, MELD score, and MELD-Na score had higher predictive values for HBV-ACLF than did CTP classification or KCH criteria. Furthermore, the MELD-ICGR15 model was better than any single parameter model for predicting the short-term prognosis of patients with HBV-ACLF.

Acute-On-Chronic Liver Failure ; diagnosis ; virology ; Adult ; Aged ; End Stage Liver Disease ; Female ; Hepatitis B ; complications ; Humans ; Indocyanine Green ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Young Adult

The role of general practitioners in the UK was analyzed and we found that in the UK, there was normalized general medical education system, perfect general practitioner training sys-tem, specific responsibilities and assessment index, close liaison group between primary and secondary care, strong economic supporting measures and high degree of recognition. Therefore, to deepen med-ical reform and improve basic medical service, we must accelerate general practitioners training, im-prove practice ability of general practitioners, establish the first-treatment system in community, reit-erate role of gatekeeper, enhance the payment of general practitioner and increase their sense of iden-tity. At the same time, we must strengthen the informatization construction, set up the first-treatment in the community and the patency of two-way referral system.

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.

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.

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 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 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.