ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） _1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L^-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg^-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

Diabetic peripheral neuropathy is a common diabetic complication.Presently,our understanding of its pathogenesis is incomplete,and there are no effective treatment options.In-depth research requires the use of animal experiments.The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments into type 2 diabetic peripheral neuropathy.However,but there has been a lack of systematic interrogation and analysis of the evaluation method used with type 2 diabetic peripheral neuropathy models.Therefore,the author reviewed the recent data,summarized and analyzed the evaluation method used for animal models of type 2 diabetic peripheral neuropathy of small and large nerve fibers,and proposed future directions for development,providing a reference for related research.

Myocardial infarction can lead to permanent loss of cardiomyocytes and depressed pumping efficiency of the heart.Due to the extremely limited self-renewal potential of cardiomyocytes,the capability of cardiac repair after ischemic injury is extremely low.Mesenchymal stem cells,one of the widely sourced,easily isolated,extracted and cultured stem cells,are regarded as an ideal source of stem cells for the treatment of myocardial infarction owing to their beneficial paracrine effects.However,the cardioprotective efficacy of mesenchymal stem cells and their derivatives observed in animal models has not been fully translated into visible clinical benefits for patients with myocardial infarction.Recently,mesenchymal stem cell-based cardiac tissue engineering has been widely used in cardiac regenerative medicine and demonstrated excellent cardiac repair potential in infarcted hearts.This article reviews recent research progress on the application of tissue engineering strategies to improve the cardiac repair efficacy of mesenchymal stem cells and their derivatives,aiming to provide evidences for exploring potential strategies that can realize the efficient clinical benefits of mesenchymal stem cell-treatment.

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

Red blood cells(RBCs)are the primary mediators of oxygen transport in the human body,and their function is mainly achieved through conformational changes of hemoglobin(Hb).Hb is a tetramer composed of four subunits,with HbA being the predominant Hb in healthy adults,existing in two forms:tense state(T state)and relaxed state(R state).Endogenous regulators of Hb conformation include 2,3-diphosphoglyceric acid,carbon dioxide,protons,and chloride ions,while exogenous regulators include inositol hexaphosphate,inositol tripyrophosphate,benzabate,urea derivative L35,and vanillin,each with different mechanisms of action.The application of Hb conformational regulators provides new insights into the study of hypoxia oxygen supply issues and the treatment of sickle cell disease.

Objective To observe the effect of Buyang Huanwu Decoction on hippocampal tissue structure and blood perfusion in rats with focal cerebral ischemia using multi-modal MRI;To analyze the mechanism of Buyang Huanwu Decoction on hippocampal neuroplasticity combined with the expression changes of neuroplasticity proteins and glucose metabolism related transporters.Methods Focal cerebral ischemia rat model induced by right middle cerebral artery occlusion were established.The rats were divided into sham-operation group,sham-operation+Buyang Huanwu Decoction group,model group and model+Buyang Huanwu Decoction group.The rats in the sham-operation group and model group were given normal saline for 30 days,and those in the sham-operation+Buyang Huanwu Decoction group and model+Buyang Huanwu Decoction group were given Buyang Huanwu Decoction for 30 days.T2 mapping imaging was used to detect the changes in hippocampal tissue structure,the changes of cerebral blood perfusion in hippocampus were detected by arterial spin labeling imaging,Western blot was used to detect the protein expressions of SYN,GAP-43,glucose transporters and MCT.Results Compared with the sham-operation group,the T2 relaxation time of the right and left hippocampus in the model group rats significantly increased(P<0.01,P<0.001),the blood flow in the right hippocampus was significantly reduced(P<0.05),the protein expressions of SYN,GAP-43,MCT4 and MCT2 in the right hippocampus were significantly decreased(P<0.01,P<0.001),the protein expressions of GLUT1 and GLUT3 in bilateral hippocappal tissue significantly decreased(P<0.05,P<0.01,P<0.001).Compared with the model group,the T2 relaxation time in the right hippocampus of rats in model+Buyang Huanwu Decoction group was significantly reduced(P<0.05),the blood flow in the right hippocampus significantly increased(P<0.05),the protein expressions of SYN,GAP-43,GLUT1 and GLUT3 in bilateral hippocampal tissues significantly increased(P<0.01,P<0.001),and the protein expressions of MCT4 and MCT2 in right hippocampal tissue significantly increased(P<0.01,P<0.001).Conclusion Buyang Huanwu Decoction can alleviate hippocampal injury in rats with focal cerebral ischemia,which may be related to improving blood perfusion,up-regulating neuroplasticity-related proteins,promoting hippocampal axon regeneration and synaptic remodeling,regulating energy metabolism of nerve cells.

The technology of three-dimensional(3D)printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering,industrial design,and biomedicine.In biomedical science,several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery.For example,3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies,surgical simulation,intraoperative navigation,medical training,and patient education.Moreover,cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs.With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery,we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective:To report a case of Kufor-Rakeb syndrome caused by novel ATP13A2 mutation, collect the cases related to ATP13A2 gene mutation published in recent years, summarize the clinical manifestations of the disease, and broaden the clinical diagnostic thinking. Methods:The clinical manifestations of a newly diagnosed patient with Kufor-Rakeb syndrome caused by ATP13A2 gene mutation admitted to Zhongda Hospital, Southeast University on November 26, 2021, were summarized. The related cases of ATP13A2 mutation published from January 2000 to December 2021 were searched through the PubMed and CNKI databases using the keywords "ATP13A2" and "Parkinson′s disease". The onset age, clinical symptoms, family history, genetic testing, and levodopa responsiveness results of the patients were collected. Results:The patient is a 52-year-old female with the main clinical symptoms of static tremor and bradykinesia. Physical examination showed a gear like increase in muscle tension in the right upper limb, involuntary shaking of the right hand and slow movement. She had good responsiveness to levodopa, and the magnetic resonance imaging and susceptibility weighted imaging of the head showed a lack of clear observation of bilateral black matter swallowtail sign. Whole exome sequencing showed that mutations c.3010A>G (p.S1004G) and c.1195+5G>A (splice) were found in the ATP13A2 gene, both of which were not reported. The c.3010A>G (p.S1004G) mutation originated from the mother, and the c.1195+5G>A (splice) mutation originated from the father. In the retrospective literature review, a total of 10 cases were collected, with onset ages ranging from 18 months to 24 years. Among them, 4/10 patients′ parents married close relatives, and the clinical manifestations were mainly motor symptoms of Parkinson′s disease. In addition, 5/10 patients had cognitive dysfunction, and 3/10 patients had mental symptoms. And demonstrations of most patients′ magnetic resonance imaging were normal in the early stage of the disease, and as the disease progressed, some patients′ imaging results showed specific changes, such as whole brain atrophy and changes in the corpus callosum. Meanwhile, 8/10 patients showed good responsiveness to levodopa. Conclusions:Kufor-Rakeb syndrome is a special type of adolescent levodopa responsive Parkinson′s disease caused by ATP13A2 mutation, which is an autosomal recessive disorder. In addition to motor symptoms such as static tremor and bradykinesia, its clinical manifestations may also be accompanied by non motor symptoms such as cognitive and psychiatric disorders. The disease responds well to treatment with levodopa.