Genetics of acute and chronic pancreatitis: An update

Progress made in identifying the genetic susceptibility underlying acute and chronic pancreatitis has benefitted the clinicians in understanding the pathogenesis of the disease in a better way. The identification of mutations in cationic trypsinogen gene(PRSS1 gene; functional gain mutations) and serine protease inhibitor kazal type 1(SPINK1 gene; functional loss mutations) and other potential susceptibility factors in genes that play an important role in the pancreatic secretory functions or response to inflammation during pancreatic injury has changed the current concepts and understanding of a complex multifactorial disease like pancreatitis. An indi-vidual's susceptibility to the disease is governed by ge-netic factors in combination with environmental factors. Candidate gene and genetic linkage studies have iden-tified polymorphisms in cationic trypsinogen(PRSS1), SPINK1, cystic fibrosis trans-membrane conductance regulator(CFTR), Chymotrypsinogen C(CTRC), Ca-thepsin B(CTSB) and calcium sensing receptor(CASR). Individuals with polymorphisms in the mentioned genes and other as yet identified genes are at an enhanced risk for the disease. Recently, polymorphisms in genes other than those involved in "intra-pancreatic trypsin regulatory mechanism" namely Claudin-2(CLDN2) andCarboxypeptidase A1(CPA1) gene have also been iden-tified for their association with pancreatitis. With ever growing number of studies trying to identify the genetic susceptibility in the form of single nucleotide polymor-phisms, this review is an attempt to compile the avail-able information on the topic.

Genetic Evidence for Causal Association Between Hypertension and Chronic Pain:A Bidirectional Two-Sample Mendelian Randomization Study

Objective The extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed.In the present study,Mendelian randomization(MR)was employed to examine the potential causal relationship between hypertension and risk of chronic pain.Methods The study data were derived from the pooled dataset of the genome-wide association study(GWAS),enabling the evaluation of the causal effects of hypertension on various types of chronic pain including chronic headache as well as chest,abdominal,joint,back,limb,and multisite chronic pain.We performed a bidirectional two-sample MR analysis using random effect inverse variance weighting(IVW),MR-Egger,weighted median,and weighted mode,quantified by odds ratio(OR).Results Genetically predicted essential hypertension was associated with an increased risk of chronic headache(OR=1.007,95%CI:1.003-1.011,P=0.002)and limb pain(OR=1.219,95%CI:1.033-1.439,P=0.019).No potential causal associations were identified between chronic pain and essential hypertension in the reverse direction MR(P>0.05).In addition,there was no potential causal association between secondary hypertension and chronic pain(P>0.05).Conclusion This study provided genetic evidence that a unidirectional causal relationship exists between essential hypertension and the increased risks of chronic headache and limb pain,and no causal relationship was found between secondary hypertension and chronic pain.These findings offer theoretical underpinnings for future research on managing hypertension and chronic pain.

An efficient method for constructing a random insertional mutant library for forward genetics in Nannochloropsis oceanica

Insertional mutation,phenotypic evaluation,and mutated gene cloning are widely used to clone genes from scratch.Exogenous genes can be integrated into the genome during non-homologous end joining(NHEJ)of the double-strand breaks of DNA,causing insertional mutation.The random insertional mutant library constructed using this method has become a method of forward genetics for gene cloning.However,the establishment of a random insertional mutant library requires a high transformation efficiency of exogenous genes.Many microalgal species show a low transformation efficiency,making constructing random insertional mutant libraries difficult.In this study,we established a highly efficient transformation method for constructing a random insertional mutant library of Nannochloropsis oceanica,and tentatively tried to isolate its genes to prove the feasibility of the method.A gene that may control the growth rate and cell size was identified.This method will facilitate the genetic studies of N.oceanica,which should also be a reference for other microalgal species.

Interaction between diet and genetics in patients with inflammatory bowel disease

In this editorial,we comment on the article by Marangoni et al,published in the recent issue of the World Journal of Gastroenterology 2023;29:5618-5629,about“Diet as an epigenetic factor in inflammatory bowel disease”.The authors emphasized the role of diet,especially the interaction with genetics,in promoting the inflam-matory process in inflammatory bowel disease(IBD)patients,focusing on DNA methylation,histone modifications,and the influence of microRNAs.In this editorial,we explore the interaction between genetics,gut microbiota,and diet,in an only way.Furthermore,we provided dietary recommendations for patients with IBD.The Western diet,characterized by a low fiber content and deficiency the micronutrients,impacts short-chain fatty acids production and may be related to the pathogenesis of IBD.On the other hand,the consumption of the Mediter-ranean diet and dietary fibers are associated with reduced risk of IBD flares,particularly in Crohn’s disease(CD)patients.According to the dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases(IOIBD),the regular consumption of fruits and vegetables while reducing the consumption of saturated,trans,dairy fat,additives,processed foods rich in maltodextrins,and artificial sweeteners containing sucralose or saccharine is recommended to CD patients.For patients with ulcerative colitis,the IOIBD recommends the increased intake of natural sources of omega-3 fatty acids and follows the same restrictive recommendations aimed at CD patients,with the possible inclusion of red meats.In conclusion,IBD is a complex and hetero-geneous disease,and future studies are needed to elucidate the influence of epigenetics on diet and microbiota in IBD patients.

A Theory of Bio-Quantum Genetics

The physical mechanism of heredity or inheritance of genes is a quantum mechanical and/or quantum computational process. A theory of bio-quantum genetics is established in this paper. Principle of Bio-quantum Genetics is suggested. I propose and define the soft-genes of genetics controlling the processes of heredity or inheritance of genes. This research deals with the quantum mechanisms of Mendel plant heredity and family inheritance as examples of bio-quantum genetics, deepening our understanding of heredity or inheritance. I believe that more contributions will be made to promote researches of bio-quantum genetics or quantum biology at large.

The Practice and Exploration of Applying EBM to Bilingual Teaching of Medical Genetics at OSBCM

In the process of teaching medical genetics of undergraduate clinical medicine, the practice and exploration of applying EBM to the bilingual teaching of OSBCM medical genetics are carried out. Using CBL and PBL as the carrier can make up for the shortcomings of a single teaching mode, synthesize the advantages of multiple teaching modes. It starts from integrating the basic theoretical knowledge of medicine and clinical practice knowledge, improving students’ bilingual level of medical genetics, cultivating students’ literature retrieval ability, and promoting early clinical, multi-clinical and repeated clinical consciousness for medical students. Therefore, it is more conducive to cultivate students’ ability to learn independently, accurately analyze and solve problems, improve medical students’ clinical thinking ability and scientific research awareness, improve medical students’ ability of international communication, and lay a solid foundation for improving medical students’ future post competence, innovative spirit and lifelong learning ability.

Pharmacological intervention for chronic phase of spinal cord injury

Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.

Mimicking aneurysm in a patient with chronic occlusion of the left middle cerebral artery

The chronic occlusion of intracranial arteries generally has no or mild clinical symptoms,and the clinical symptoms of acute cerebral artery occlusion are mostly manifested as severe cerebral infarction symptoms,which often make early diagnosis difficult,thus losing the best treatment opportunity.Once cerebral infarction occurs,the consequences are difficult to recover.This is also an important reason for the high misdiagnosis rate and mortality of this disease.In this paper,the characteristics of the disease were analyzed to provide clinical reference.

Challenges and improvement strategies in the hospitalization of chronic multimorbid patients

BACKGROUND Addressing the growing challenge of hospitalizing chronic multimorbid patients,this study examines the strain these conditions impose on healthcare systems at a local level,focusing on a pilot program.Chronic diseases and complex patients require comprehensive management strategies to reduce healthcare burdens and improve patient outcomes.If proven effective,this pilot model has the potential to be replicated in other healthcare settings to enhance the management of chronic multimorbid patients.AIM To evaluate the effectiveness of the high complexity unit(HCU)in managing chronic multimorbid patients through a multidisciplinary care model and to compare it with standard hospital care.METHODS The study employed a descriptive longitudinal approach,analyzing data from the Basic Minimum Data Set(BMDS)to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout 2022.The HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity post-discharge.RESULTS The study employed a descriptive longitudinal approach,analyzing data from the BMDS to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout 2022.The HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity post-discharge.CONCLUSION This study demonstrates the effectiveness of the HCU in managing patients with complex chronic diseases through a multidisciplinary approach.The coordinated care provided by the HCU results in improved patient outcomes,reduced unnecessary hospitalizations,and better management of patient complexity.The superiority of the HCU compared to standard care is evident in key outcomes such as fewer readmissions and higher patient satisfaction,reinforcing its value as a model of care to be replicated.

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

A Preliminary Study on Conservation Genetics of Three Endangered Orchid Species

采用随机扩增多态DNA(RAPD)分析研究了中国 3种珍稀濒危兰科植物硬叶兜兰 (PaphiopedilummicranthumTangetWang)、麻栗坡兜兰 (P .malipoenseS .C .ChenetTsi)和独花兰 (ChangnieniaamoenaChien)的遗传多样性与群体遗传结构。 12个RAPD引物在 2种兜兰中共扩增出 131条带。对 4个硬叶兜兰群体的检测表明其物种水平的多态条带百分率 (PPB)为 71.6 % ,Nei的基因多样度 (h)为 0 .2 171,Shannon多样性指数 (I)为 0 .330 1;4个群体的平均多样性水平为PPB =45 .2 % ,h =0 .145 7,I =0 .2 2 0 4,低于远交兰花的平均水平。在总遗传变异中 ,群体间遗传变异占 2 0 .31% ,略高于远交物种的平均水平。在物种水平上 ,麻栗坡兜兰的PPB为 49.5 % ,h为 0 .1174,I为0 .176 4,均大大低于硬叶兜兰。对 11个独花兰群体采用 16个RAPD引物共扩增出 119条带。物种水平PPB =76 .5 % ,h =0 .1941,I=0 .30 5 8;在群体水平上 ,上述 3个指标的平均值则分别为 37.2 %、0 .1197和 0 .1810 ,均低于远交兰花的平均水平。群体间的遗传变异占 45 .2 7% ,遗传分化明显高于远交物种的平均水平。导致 3个物种遗传多样性偏低而群体间遗传分化较高的主要原因在于人为的过度采挖和生境的片断化。

A Preliminary Study on Conservation Genetics of Endangered Vatica guangxiensis (Dipterocarpaceae)

运用 2 0个 10碱基随机引物 ,对中国龙脑香科 (Dipterocarpaceae)特有的珍稀濒危植物版纳青梅 (VaticaguangxiensisX .L .Mo)进行了RAPD多态性分析。 3个自然居群和 1个迁地保护居群 (分布于云南和广西 )共扩增出2 31个位点 ,多态位点所占比例 (PPB)为 5 3.6 8% ;观察等位基因数na =1.5 36 8,有效等位基因数ne =1.2 878,Nei基因多样性指数h为 0 .16 86 ,居群内的遗传多样性水平较低。基于AMOVA和POPGENE的结果均表明居群内的遗传变异大于居群间的遗传变异。居群内的遗传变异为 5 5 .0 9% ,居群间的变异为 44 .91% (AMOVA) ;基因分化系数Gst为 0 .3746 (POPGENE) ,表明居群间存在高水平的遗传分化。研究结果对该濒危植物的保护有重要意义。考虑到低水平的遗传多样性和高水平的居群分化 ,通过居群间种子和幼苗的交换来促进基因流是可行的保护方案。迁地保护居群 (ML)不具最高的遗传多样性 ,表明为了保护此濒危物种的全部遗传变异 。

Compound Genetics Annealing Optimal Algorithm for Realization of Locus Deduction of a Plane Link

A compound algorithm of genetic annealing is designed for optimizing the luffing mechanism locus of a plane link by means of random optimal algorithm, genetic and annealing algorithm. The computing experiment shows that the algorithm has much better steady convergence performance of optimal process and can hunt out the global optimal solution by biggish probability for objective function of multi peak value.

Study on the Acute Toxicity and Genetics Toxicity of Bensulfuronk-methyl on Danio rerio

[Objective] The aim was to study the effect of bensulfuron-methyl herbicide on acute toxicity and genetics toxicity of Danio redo. [ Method] Median lethal concentration was calculated by acute toxicity test, and analyzing the herbicide whether existing in potential toxicity to aquatic organisms or not. Based on the study of acute toxicity, genetics toxicity was carried out, by calculating the micronucleus rate to judge bensulfuron-methyl herbicide whether existing in potential toxicity or not. [ Result ] The LD5o （24 h and 48 h） of bensulfuron-methyl herbicide are 0.698 ml/L and 0.637 ml/L respectively, the safe concentration was 0.159 ml/L. The results on the effects of micronucleus （MN） in erythrocytes of Danio redo induced by bensulfuron-methyl at different times and different concentrations showed that the MN rate of control group was 0.010 3%, the highest MN rate of experimental group reached to 0. 372%, it also indicated that bensulfuron-methyl herbicide had genetics toxicity to Danio redo. At the same detection time, there was dose-effect relationship of MN rate in erythrocytes between treatment and control groups with different concentrations. In the same treatment group, the MN rate in erythrocytes reached to peak value at 24 h, and decreased at 48 h and 72 h with the infection time was prolonged. [ Conclusion ] The study provides some basis for scientifically selecting and reasonably using herbicide.

国外遗传学教材“Genetics”一书 简评

遗传学是生命科学中最富于综合性的中心学科之一，也是现代生命科学发展最为迅速的学科之一。以遗传学为基础发展起来的生物技术正处于浩浩荡荡的新发明浪潮的初期，分子遗传学及生物技术发明创造高潮将要持续到21世纪的很长一段时间，并将对医疗、农业、环保等产生革命性的影响。

Morphology and Genetics of Rice in Response to High Temperature at Flowering Period

High temperature stress is one of major abiotic stresses limiting rice productivity,especially at the flowering period.Understanding mechanisms of rice adaptation to heat stress would facilitate the development of heat-tolerance cultivars for improving yield in a warmer world.Rice heat stress responses are very complex.Interactions between structure,function and the environment need to be investigated at the apparent and molecular levels in order to obtain a full picture.In this review,we summarized the current knowledge on the morphology and genetic basis of heat tolerance in reproductive tissues of rice at the flowering time,and some morphologic characters for increasing thermotolerance in rice via conventional breeding are outlined.

Epidemiology, genetics and treatments for myopia

Myopia is a significant public health problem and its prevalence is increasing over time and genetic factors in disease development are important. The prevalence and incidence of myopia within sampled population often varies with age, country, sec race, ethnicity, occupation, environment, and other factors. Myopia growth is under a combination of genes and their products in time and space to complete the coordination role of the guidance. Myopia-related genes include about 70 genetic loci to which primary myopias have been mapped, although the number is constantly increasing and depends to some extent on definition. Of these, several are associated with additional abnormalities, mostly as part of developmental syndromes. These tend to result from mutations in genes encoding transcriptional activators, and most of these have been identified by sequencing candidate genes in patients with developmental anomalies. Currently, collagen alpha-1 chain of type I(COL1A1), collagen alpha-1 chain of type II(COL2A1), actin, alpha, cardiac muscle 1 (ACTC1), paired box gene 6 (PAX6) and NIPBL (nipped-B homolog), and so on have been mapped. Myopia is most commonly treated with spectacles or glasses. The most common surgical procedure performed to correct myopia is laser keratomileusis (LASIK). This review of the recent advances on epidemiology, genetic locations and treatments of myopia are summarized.

From chronic liver disorders to hepatocellular carcinoma: Molecular and genetic pathways

Hepatocarcinogenesis is a process attributed to progressive genomic changes that alter the hepatocellular phenotype producing cellular intermediates that evolve into hepatocellular carcinoma (HCC). During the preneoplastic phase, the liver is often the site of chronic hepatitis and/or cirrhosis, and these conditions induce liver regeneration with accelerated hepatocyte cycling in an organ that is otherwise proliferatively at rest. Hepatocyte regeneration is accelerated by upregulation of mitogenic pathways involving molecular and genetic mechanisms. Hepatic growth factors, inhibitors and triggers may also play a role. This process leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that have telomerase reexpression, microsatellite instability, and occasionally structural aberrations in genes and chromosomes. Development of dysplastic hepatocytes in foci and nodules and the emergence of HCC are associated with the accumulation of irreversible structural alterations in genes and chromosomes even if the genomic basis of the malignant phenotype is largely heterogeneous. Therefore, a malignant hepatocyte phenotype may be produced by changes in genes acting through different regulatory pathways, thus producing several molecular variants of HCC. On these bases, a key point for future research will be to determine whether the deletions are specific, due to particular loci in the minimally deleted regions of affected chromosome arms, or whether they are nonspecific with loss of large portions of chromosomes or entire chromosome arms leading to passive deletion of loci. The final aim is the possibility of identifying a step where carcinogenetic processes could be terminated.

Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention

Carcinoma of the stomach is still the second most common cause of cancer death worldwide, although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric cancer varies in different parts of the world and among various ethnic groups. Despite advances in diagnosis and treatment, the 5-year survival rate of stomach cancer is only 20 per cent. Stomach cancer can be classified into intestinal and diffuse types based on epidemiological and clinicopathological features. The etiology of gastric cancer is multifactorial and includes both dietary and nondietary factors. The major diet-related risk factors implicated in stomach cancer development include high content of nitrates and high salt intake. Accumulating evidence has implicated the role of Helicobacter pylori (H. pylori) infection in the pathogenesis of gastric cancer. The development of gastric cancer is a complex, multistep process involving multiple genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, and signaling molecules. A plausible program for gastric cancer prevention involves intake of a balanced diet containing fruits and vegetables, improved sanitationand hygiene, screening and treatment of H. pylori infection, and follow-up of precancerous lesions. The fact that diet plays an important role in the etiology of gastric cancer offers scope for nutritional chemoprevention. Animal models have been extensively used to analyze the stepwise evolution of gastric carcinogenesis and to test dietary chemopreventive agents. Development of multitargeted preventive and therapeutic strategies for gastric cancer is a major challenge for the future.

Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma

Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellu-lar carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV coinfected patients show a higher prevalence of the lowproducer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.