ObjectiveTo investigate the association of the single nucleotide polymorphism （SNP） of the insulin-like growth factor binding protein-3 （IGFBP3） gene at rs10225396 （A>G） locus with the susceptibility to hepatocellular carcinoma， as well as its potential molecular regulatory mechanisms， and to provide novel genetic biomarkers and a theoretical basis for early screening and precise targeted therapy for hepatocellular carcinoma. MethodsA total of 192 patients with hepatocellular carcinoma who were admitted to The Affiliated Hospital of Yanbian University and Yanbian Cancer Hospital from January 2009 to August 2016 were enrolled as experimental group， and 190 healthy individuals who underwent physical examination in Physical Examination Center of Yanbian Hospital during the same period of time were enrolled as control group. Peripheral blood samples were collected from all subjects， and after DNA was extracted from whole blood， the DNA samples meeting quality standards were sent to Beijing Genomics Institute Research Center Co.， Ltd.， for Mass ARRAY mass spectrometry， while genotyping was completed. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. A binary Logistic regression model was used to analyze the association of the SNP of the IGFBP3 gene at rs10225396 locus with the susceptibility to hepatocellular carcinoma， and odds ratio （OR） and 95% confidence interval （CI） were calculated to assess the risk of developing hepatocellular carcinoma in individuals carrying different genotypes. ResultsThere were two alleles （G and A） at the rs10225396 locus of the IGFBP3 gene， yielding the three genotypes of AA， AG， and GG， and its genotype distribution was consistent with the Hardy-Weinberg equilibrium （χ²=0.072， P=0.789）. The stratified genetic analysis showed that carriers of the IGFBP3 rs10225396 AA genotype had a significant increased risk of hepatocellular carcinoma among individuals of age <63 years， male sex， smoking history， drinking history， and the Chinese Korean population （all P<0.001）. The binary Logistic regression analysis showed that after adjustment for related risk factors in the codominant model， the population with genotype AG and GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）， and in the dominant model， the population with genotype AG+GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）. ConclusionThrough a genotyping analysis of hepatocellular carcinoma patients and healthy individuals in Yanbian Korean Autonomous Prefecture of Jilin Province， China， this study shows that genotype AA at rs10225396 locus of the IGFBP3 gene is significantly associated with the susceptibility to hepatocellular carcinoma， and this genotype can significantly increase the risk of developing hepatocellular carcinoma with the presence of specific risk factors， which provides a potential genetic marker for early screening and precise treatment of hepatocellular carcinoma.

BACKGROUND:The problem of intervertebral disc injury and degeneration has been studied in many ways.Many studies have shown that intervertebral disc injury and degeneration is driven by mechanical loading factors.However,the potential relationship between common phenotypes of intervertebral disc injury and degeneration and mechanical loading factors has been rarely summarized. OBJECTIVE:To summarize the types of common structural abnormalities exhibited by intervertebral disc injury and degeneration in the published literature,and sum up the potential links to the types of mechanical loading that lead to these structural abnormalities in in vitro and ex vivo experimental studies. METHODS:Using the terms"intervertebral disc failure,intervertebral disc injury,mechanical load,mechanical factor,load factor,biomechanics"as Chinese and English key words in PubMed,CNKI,and WanFang databases,articles related to intervertebral disc injury degeneration and mechanical load factors were retrieved.Literature screening was performed according to the inclusion and exclusion criteria,and 88 articles were finally included. RESULTS AND CONCLUSION:(1)Common structural abnormalities of intervertebral discs include decreased intervertebral disc height,disc bulge,osteophyte formation,annulus fibrosus tear,intervertebral disc herniation or disc prolapse,endplate damage,Schmorl nodes and intervertebral disc calcification.Intervertebral discs are susceptible to mechanical load types such as compression,bending,axial rotation,and compound loads.(2)The compressive load mainly causes the decrease of the proteoglycan content and the water-binding ability of the intervertebral disc,leading to the decrease or swelling of the intervertebral disc and further damage and degeneration of the intervertebral disc.In addition,the excessive compressive load causes greater damage to the endplate.(3)Bending load and axial rotation load damage the annulus fibrosus more than the endplate,and prolonged or repeated bending loads can cause tearing of the fibrous annulus and herniation or prolapse of the intervertebral disc,while pure axial rotation loads can induce less damage to the intervertebral disc and only cause the tear of the annulus fibrosus.(4)However,when different load types act in combination,it is more likely to result in high stress on the disc and a greater risk of disc injury.(5)Injury and degeneration of the intervertebral disc present progressive structural damage,and early prevention and protection are particularly important in clinical practice.Future tissue engineering research can start with early repair of the intervertebral disc.

Objective:To explore the effects of different polymers on in vitro biomimetic mineralization of small intestinal submucosa(SIS)scaffolds,and to evaluate the physicochemical properties and bio-compatibility of the SIS scaffolds.Methods:The SIS scaffolds prepared by freeze-drying method were im-mersed in simulated body fluid(SBF),mineralized liquid containing polyacrylic acid(PAA)and mine-ralized liquid containing PAA and polyaspartic acid(PASP).After two weeks in the mineralized solu-tion,the liquid was changed every other day.SBF@SIS,PAA@SIS,PAA/PASP@SIS scaffolds were ob-tained.The SIS scaffolds were used as control group to evaluate their physicochemical properties and bio-compatibility.We observed the bulk morphology of the scaffolds in each group,analyzed the microscopic morphology by environment scanning electron microscopy and determined the porosity and pore size.We also analyzed the surface elements by energy dispersive X-ray spectroscopy(EDX),analyzed the struc-ture of functional groups by Flourier transformed infrared spectroscopy(FTIR),detected the water ab-sorption rate by using specific gravity method,and evaluated the compression strength by universal me-chanical testing machine.The pro-cell proliferation effect of each group of scaffolds were evaluated by CCK-8 cell proliferation method.Results:Under scanning electron microscopy,the scaffolds of each group showed a three-dimensional porous structure with suitable pore size and porosity,and crystal was observed in all the mineralized scaffolds of each group,in which the crystal deposition of PAA/PASP@SIS scaffolds was more regular.At the same time,the collagen fibers could be seen to thicken.EDX analysis showed that the characteristic peaks of Ca and P were found in the three groups of mineralized scaffolds,and the highest peaks were found in the PAA/PASP@SIS scaffolds.FTIR analysis proved that all the three groups of mineralized scaffolds were able to combine hydroxyapatite with SIS.All the scaf-folds had good hydrophilicity.The compressive strength of the mineralized scaffold in the three groups was higher than that in the control group,and the best compressive strength was found in PAA/PASP@SIS scaffold.The scaffolds of all the groups could effectively adsorb proteins,and PAA/PASP@SIS group had the best adsorption capacity.In the CCK-8 cell proliferation experiment,the PAA/PASP@SIS scaffold showed the best ability to promote cell proliferation with the largest number of living cells observed.Con-clusion:Compared with other mineralized scaffolds,PAA/PASP@SIS scaffolds prepared by mineralized solution containing both PAA and PASP have better physicochemical properties and biocompatibility and have potential applications in bone tissue engineering.

Objective To analyze the correlation between high signal intensity of infrapatellar fat pad(IPFP)and symptoms and structural changes of osteoarthritis of the knee in patients with osteoarthritis of the knee based on image digitization.Methods Imaging and clinical data of patients with knee osteoarthritis(KOA)were retrospectively analyzed.The differences in knee osteoarthritis symptoms and structural changes in patients with different IPFP high signal intensities were compared,and the relationship between IPFP high signal intensity changes and knee osteoar-thritis symptoms as well as structural changes was also analyzed.Results A total of 219 patients(268 knees)were collected and completed imaging measurements and evaluations,and the median IPFP high signal intensity(27.40％)was used to compare the groups.The IPFP high signal intensity ≥ 27.40％group had a significantly higher degree of tibial cartilage damage,changes in knee angle,pain,and total scores on the osteoarthritis index(western ontario and mcMaster).universities osteoarthritis index(WOMAC)were significantly higher than those in the IPFP high signal intensity＜27.40％group,with a statistically significant difference(P＜0.05);IPFPF high signal inten-sity changes were associated with knee pain,joint line convergence angle,JLCA,and knee joint angle.Angle(JLCA),knee kellgren-Lawrence(KL)classification,and the degree of femoral and tibial cartilage damage were significantly positively correlated(P＜0.05).Conclusion In patients with KOA,there is a significant correlation between IPFP high signal intensity changes and knee pain symptoms as well as structural changes,which may be an important factor influencing the progression of KOA.

Objective To analyze the correlation between high signal intensity of infrapatellar fat pad(IPFP)and symptoms and structural changes of osteoarthritis of the knee in patients with osteoarthritis of the knee based on image digitization.Methods Imaging and clinical data of patients with knee osteoarthritis(KOA)were retrospectively analyzed.The differences in knee osteoarthritis symptoms and structural changes in patients with different IPFP high signal intensities were compared,and the relationship between IPFP high signal intensity changes and knee osteoar-thritis symptoms as well as structural changes was also analyzed.Results A total of 219 patients(268 knees)were collected and completed imaging measurements and evaluations,and the median IPFP high signal intensity(27.40％)was used to compare the groups.The IPFP high signal intensity ≥ 27.40％group had a significantly higher degree of tibial cartilage damage,changes in knee angle,pain,and total scores on the osteoarthritis index(western ontario and mcMaster).universities osteoarthritis index(WOMAC)were significantly higher than those in the IPFP high signal intensity＜27.40％group,with a statistically significant difference(P＜0.05);IPFPF high signal inten-sity changes were associated with knee pain,joint line convergence angle,JLCA,and knee joint angle.Angle(JLCA),knee kellgren-Lawrence(KL)classification,and the degree of femoral and tibial cartilage damage were significantly positively correlated(P＜0.05).Conclusion In patients with KOA,there is a significant correlation between IPFP high signal intensity changes and knee pain symptoms as well as structural changes,which may be an important factor influencing the progression of KOA.

Objective: Effective prevention and control measures are essential to contain outbreaks of infectious diseases, such as coronavirus disease (COVID-19). Understanding the characteristics of case clusters can contribute to determining which prevention and control measures are needed. This study describes the characteristics of COVID-19 case clusters in Malaysia, the method used to detect a cluster’s index case and the mode of early transmission, using the seven cluster categories applied in Malaysia. Methods: This cross-sectional study collected publicly available data on COVID-19 clusters occurring in Malaysia from 1 March 2020 to 31 May 2021. The characteristics of cases were described by category, and their associations with several outcomes were analysed. Descriptive analyses were performed to explore the method used to detect the index case and the mode of early transmission, according to cluster category. Results: A total of 2188 clusters were identified. The workplace cluster category had the largest proportion of clusters (51.5%, 1126/2188 clusters), while the custodial settings category had the largest median cluster size (178 cases per cluster) and longest median duration of cluster (51 days). The high-risk groups category had the highest mortality. There were significant differences in cluster size, duration and rate of detection across the categories. Targeted screening was most commonly used to detect index cases, especially in custodial settings, and in imported and workplace clusters. Household–social and social–workplace contacts were the most common modes of early transmission across most categories. Discussion: Targeted screening might effectively reduce the size and duration of COVID-19 clusters. Measures to prevent and control COVID-19 outbreaks should be continually adjusted based on ongoing assessments of the unique context of each cluster.

Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing. This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve (B. breve). A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing. The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography (micro-CT). Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay (ELISA). The senescence and biological functions were tested in oral mucosal stem cells (OMSCs) treated with sunitinib. Ligated loop experiments were used to investigate the effect of oral B. breve. Neutralizing antibody for interleukin-10 (IL-10) was used to prove the critical role of IL-10 in the pro-healing process derived from B. breve. Results showed that sunitinib caused oral mucosal wound healing impairment in mice. In vitro, sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation, migration, and differentiation. Oral administration of B. breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells (DCs)-derived IL-10. IL-10 reversed cellular senescence caused by sunitinib in OMSCs, and IL-10 neutralizing antibody blocked the ameliorative effect of B. breve on oral mucosal wound healing under sunitinib treatment conditions. In conclusion, sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B. breve could improve wound healing impairment via intestinal DCs-derived IL-10.
Animals ; Mice ; Interleukin-10 ; Bifidobacterium breve ; Up-Regulation ; Angiogenesis Inhibitors ; Sunitinib ; X-Ray Microtomography ; Administration, Oral ; Wound Healing ; Antibodies, Neutralizing

Grey literature is a valuable source of information for evidence synthesis in public health, particularly when swift action is needed to address issues. In 2020, the COVID-19 pandemic was an example where rapid knowledge sharing was quintessential as the world grappled with the management of a novel coronavirus that was spreading at an alarming rate. To document and contextualise the health systems strategies used to address the COVID-19 pandemic in Malaysia from January 2020 to April 2020, we conducted a rapid review of publicly available documents from WHO Global Research on Coronavirus Disease (COVID-19) (WHO database), official government websites and local newspapers. This paper aims to describe the methods and discuss the lessons learnt from the review. In the early stage of the pandemic, published articles in the WHO database focused on clinical knowledge, hence we relied on grey literature as a primary source of information, mainly official government websites, which provided real-time information relevant to our study. Grey literature can be a good source of information for a rapid review of nascent and urgent topics particularly in the area of public health, however, a trade-off between comprehensiveness and efficiency has to be considered.
Gray Literature

Objective To determine if there is any difference in neuronal and glial(astrocytic and microglial)activation in the spinal cord in three rat models of neuropathic pain.Methods Twenty-four SD rats weighing 150-200 g were randomly divided into 4 groups(n=6 each):Ⅰ control group;Ⅱ chronic constrictive injury group(CCI);Ⅲ spinal nerve ligation group(SNL)and Ⅳ spared nerve injury(SNI).No operation was performed in control group.In CCI group left sciatic nerve was exposed and loosely ligated with catgut.In SNL group the L_5 spinal nerve was exposed and ligated with silk suture and cut.In SNI group tibial nerve and common fibular nerve were ligated and cut.Pain threshold was measured using plantar tactile stimulator(Ugo,Basile Co. Italy)every other day from 3 days before until 15 days after operation.50% paw withdrawal threshold was measured using up-and-down sequential mechanical stimulation of different intensity(0.45,0.70,1.20,2.00, 3.63,5.50,8.50,15.10 g)applied to the plantar surface of the injured paw.On the 15~(th) day after operation after pain threshold was measured the animals were anesthetized with intraperitoneal 10% chloral hydrate 400 mg? kg~(-1).The L_(5,6) segment of the spinal cord was isolated.Neuronal,astrocytic and microglial activation was determined by immuno-histochemistry with antibodies of c-Fos(a proto-oncogene protein),GFAP(an astrocyte marker)and OX-42(a microglial marker).Results The 50% paw withdrawal threshold reached the lowest level on the 7~(th) day after operation.The lowest level was maintained until the 15~(th) day after operation in group CCI,SNL and SNI.The 50 % paw withdrawal threshold was(14.1+1.5)g in control group,(2.5+0.5)g in CCI group, (1.5?0.6)g in group SNL and(0.8?0.4)g in group SNI.The number of c-Fos positive neurons in laminae Ⅳ-Ⅵ of dorsal horn was significantly greater in group CCI,SNL and SNI than in control group,but there was no significant difference among the 3 peripheral nerve injury groups.The activation of astrocytes and microglias in laminae Ⅰ-Ⅳ of dorsal horn was significantly increased in group CCI,SNL and SNI than in control group but there was no significant difference among the 3 peripheral nerve injury groups.Condusion There is no significant difference in activation of neurons and astrocytes and microglias in the ipsilateral dorsal horn among the 3 pain models.