Mediating effect of lifestyle on the relationship between family history and cardiovascular disease / 公共卫生与预防医学

Objective To evaluate the mediating effect of lifestyles on the association between family history and cardiovascular disease (CVD). Methods This study was based on the "Early Screening and Comprehensive Intervention of High-risk Populations of Cardiovascular Disease Project". The data were collected from 6 project sites in Hubei Province. Logistic regression analysis was used to investigate the impact of family history and lifestyle on CVD, and the relationship between family history and lifestyle. Mediation analysis was used to evaluate the mediating effect of lifestyle on the association between family history and CVD. Results A total of 5 871 subjects were included in the study from 2015 to 2016, of whom 500 (8.52%) developed CVD and 484 had family history of CVD. The risk of developing CVD was significantly increased in participants with family history of disease (OR = 1.458, P = 0.014) and in those with high level of physical activity (OR = 1.081, P = 0.026). The increase of leisure physical activity time showed a protective effect on developing CVD (OR = 0.977, P < 0.001). Participants with family history significantly increased leisure physical activity (OR = 2.085, P < 0.001), and were less likely to choose occupations with high levels of physical activity (OR = 0.524, P < 0.001). The results of mediation analysis showed that leisure physical activity and occupational physical activity mediated the relationship between family history and CVD, and the β value of the mediating effects were -0.004 (P = 0.010) and 0.002 (P = 0.045), respectively. The β value of the direct effect of family history on CVD was 0.033 (P < 0.05). Conclusion Leisure physical activity and occupational physical activity might mediate the relationship between family history and CVD. People with family history would reduce the risk of developing CVD by increasing leisure physical activity time and choosing occupations with low levels of physical activity.

The clinical value of serum GPC3 level in predicting recurrence of patients with primary hepatocellular carcinoma / 中华预防医学杂志

Objective: To investigate the clinical value of serum glypican-3 (GPC3) detection in predicting recurrence of primary hepatocellular carcinoma (HCC). Methods: Through univariate and multivariate logistic regression analysis, the patients pathologically diagnosed with HCC in our hospital from March 2019 to January 2021 were enrolled as the experimental group (n=113), and patients with follow-up time longer than 6 months were included in the prognosis group(n=64). At the same time,20 healthy individuals and 20 individuals with benign liver disease from the physical examination center were enrolled by simple random sampling as control group (n=40). The serum GPC3 and alpha-fetoprotein (AFP) levels were respectively detected by ELISA and chemiluminescence. Then, the study explored the influential factors of the recurrence in HCC patients and constructed the HCC-GPC3 recurrence predicting model by logistic regression. Results: In the research, the sensitivity of GPC3 for the diagnosis of HCC was 61.95% (70/113) and AFP was 52.21% (59/113), meanwhile, the specificity of GPC3 could reach 87.50% (35/40) and AFP was 90.00% (36/40),respectively; The serum GPC3 levels of HCC patients with progressive stage, tumor size≥3 cm, vascular cancer thrombosis and portal venous thromboembolism were significantly higher than that of HCC patients with early stage, tumor size<3 cm, vascular cancer thrombosis and portal venous thromboembolism (Z=2.677, 2.848, 2.995, 2.252, P<0.05), independent of different ages, presence or absence of ascites, peritoneal metastasis, cirrhosis, intrahepatic metastasis (Z=-1.535, 1.011, 0.963, 0.394, 1.510, P>0.05), respectively. Univariate analysis showed that there were no statistically significant differences between the recurrence group and the non-recurrence group in terms of different age, tumor size, presence or absence of vascular cancer thrombosis, ascites, peritoneal metastasis, cirrhosis and AFP levels (χ2=2.012, 0.119, 2.363, 1.041, 0.318, 0.360, Z=0.748, P>0.05); The ratio of those with the progressive stage, portal venous thromboembolism and intrahepatic metastasis and GPC3 levels were all higher in the recurrence group than in the non-recurrence group (χ2=4.338, 11.90, 4.338, Z=2.805, P<0.05).Including the above risk factors in the logistic regression model, the logistic regression analysis showed that the stage, the presence of portal venous thromboembolism,intrahepatic metastasis and GPC3 levels were correlated with the prognosis recurrence of HCC patients (Wald χ2 =4.421, 5.681, 4.995, 4.319, P<0.05), and the HCC-GPC3 recurrence model was obtained as: OcScore=-2.858+1.563×[stage]+1.664×[intrahepatic metastasis]+2.942×[ portal venous thromboembolism]+0.776×[GPC3]. According to the receiver operating characteristic curve(ROC), the area under the curve(AUC)of the HCC-GPC3 prognostic model was 0.862, which was better than that of GPC3 alone (AUC=0.704). The cut-off value of model SCORE was 0.699 (the cut-off value of GPC3 was 0.257 mg/L), furthermore, the total sensitivity and specificity of model were 83.3% and 82.4%, which were better than those of GPC3(60.0% and 79.4%).Kaplan-Meier showed that the median PFS was significantly shorter in HCC patients with high GPC3 levels (≥0.257 mg/L) and high values of the model SCORE (≥0.700) (χ2=12.73, 28.16, P<0.05). Conclusion: Besides diagnosing of HCC, GPC3 can may be an independent risk indicator for the recurrence of HCC and can more efficiently predicting the recurrence of HCC patients when combined with the stage, the presence or absence of intrahepatic metastasis and portal venous thromboembolism.

Blaps rynchopetera affects proliferation, migration, and invasion of non-small cell lung cancer: a study based on network pharmacology and in vivo and in vitro experiments / 中国中药杂志

Network pharmacology, molecular docking, and in vivo and in vitro experiments were employed to study the molecular mechanism of Blaps rynchopetera Fairmaire in the treatment of non-small cell lung cancer(NSCLC). The components of B. rynchopetera were collected by literature review, and the active components were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). PharmMapper was used to obtain the targets of the active components. The targets of NSCLC were obtained from DrugBank, GeneCards, OMIM, TTD, and PharmGKB. The Venn diagram was drawn to identify the common targets shared by the active components of B. rynchopetera and NSCLC. The "drug component-target" network and protein-protein interaction(PPI) network were constructed by Cytoscape, and the key targets were screened by Centiscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the above key targets were performed by DAVID. AutoDock and PyMOL were used for the molecular docking between the key targets and corresponding active components. A total of 31 active components, 72 potential targets, and 11 key targets of B. rynchopetera against NSCLC were obtained. The active components of B. rynchopetera had good binding activity with key targets. Further, the serum containing B. rynchopetera was prepared and used to culture human lung adenocarcinoma A549 cells. The CCK-8 assay was employed to determine the inhibition rates on the growth of A549 cells in blank control group and those exposed to different concentrations of B. rynchopetera-containing serum, cisplatin, and drug combination(B. rynchopetera-containing serum+cisplatin) for different time periods. The cell migration and invasion of A549 cells were detected by cell scratch assay and Transwell assay, respectively. Western blot was employed to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), caspase-3, cell division cycle 42(CDC42), proto-oncogene tyrosine-protein kinase SRC, and vascular endothelial growth factor(VEGF) in A549 cells. C57BL/6 mice were inoculated with Lewis cells and randomly assigned into a model control group, a B. rynchopetera group, a cisplatin group, and a drug combination(B. rynchopetera+cisplatin) group, with 12 mice per group. The body weight and the long diameter(a) and short diameter(b) of the tumor were monitored every other day during treatment, and the tumor volume(mm~3) was calculated as 0.52ab~2. After 14 days of continuous medication, the mice were sacrificed for the collection of tumor, spleen, and thymus, and the tumor inhibition rate and immune organ indexes were calculated. The tissue morphology of tumors was observed by hematoxylin-eosin(HE) staining, and the positive expression of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF in the tumor tissue was detected by immunohistochemistry. The results indicated that B. rynchopetera and the drug combination regulated the expression levels of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF to inhibit the proliferation, migration, and invasion of A549 cells and Lewis cells, thus playing a role in the treatment of NSCLC via multiple ways.

A Novel EYA1 Mutation Causing Alternative RNA Splicing in a Chinese Family With Branchio-Oto Syndrome: Implications for Molecular Diagnosis and Clinical Application

Objectives@#. Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. @*Methods@#. We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. @*Results@#. A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. @*Conclusion@#. We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

Diagnostic and prognostic value of bone marrow plasma cell morphology in patients with plasma cell myeloma / 中华检验医学杂志

Objective:To investigate the value of bone marrow plasma cell morphology in the diagnosis and prognosis of plasma cell myeloma (PCM).Method:Observational study.Collect the bone marrow morphology image reports and corresponding monoclonal protein (M protein) identification results of 1071 patients [629 males and 442 females, Median age 62 (29, 93) years] diagnosed with PCM in the outpatient and inpatient departments of Beijing Chaoyang Hospital affiliated to Capital Medical University from January 1, 2017 to February 28, 2022. Combined with Durie‐Salmon(DS) and International Staging System (ISS) of 427 patients diagnosed with PCM and overall survival time (OS) of 436, summarize the relevant plasma cell morphological characteristics. Statistical methods include chi-square test, Kruskal-Walls test, Spearman correlation analysis and Kaplan-Meier survival analysis.Result:The bone marrow morphology reports showed that the typical morphological features of peripheral blood in 573 patients with PCM included plasma cells (40.84%), immature granulocytes (30.89%), rouleaux formation in erythrocytes (68.94%) and nucleated red blood cells (8.55%). The types of bone marrow plasma cells in 1 071 patients diagnosed with PCM included 372 (34.73%) plasmablasts, 674 (62.93%)immature plasma cells, and 25 (2.34%) mature plasma cells. There is a significant positive correlation between the number of bone marrow plasma cells (proportion of nuclear cells) and the concentration of IgG and IgA type, from M protein identification( r=0.55, r=0.60, P<0.01). The proportions of M protein types in 1 071 patients with PCM from high to low were IgG (45.75%), IgA (23.53%), light chain (19.61%), IgD (4.76%), non-secretory (4.3%), biclonal (1.78%), IgE (0.19%), IgM (0.08%). The typical characteristics of the bone marrow plasma cells in various M protein types included clustered distribution, different cell body sizes, inclusions in the cytoplasm, binuclear, polynuclear, and abnormal nuclear. The proportion of plasmablasts in DSⅢ stage was 44.81% (164/366), higher than 21.57% (11/51) in DSⅡstage, and the difference was statistically significant(χ 2=10.2, P<0.05). There was a significant positive correlation between the number of bone marrow plasma cells and DS and ISS stages( r=0. 0.23, r=0.30, P<0.01). The median OS of the PCM patients in the plasmablasts group was significantly shorter than that in the immature plasma cells group [56.0 (23.0, 101.8) months vs 75.9(31.6, 121.5) months, HR=1.42,95% CI 1.05-1.91, P=0.02]. The median OS of the PCM patients in the group of tumor plasma cells burden≥37.5% was shorter than that of the tumor plasma cells burden<37.5% [75.9 (21.4, 122.6)months vs 81.3 (36.6, 108) months, HR=1.54,95% CI 1.14-2.07, P<0.05]. Conclusion:The morphology and tumor burden of bone marrow plasma cells provide an important basis for the diagnosis of PCM and can be used as a prognostic indicator for patients with PCM.

Effects of sodium arsenite on mitochondrial function and expression of SIRT1/PGC-1α pathway-related proteins in human normal liver cell / 环境与职业医学

Background Long-term exposure to arsenic can cause liver injury of varying degrees. Mitochondrial damage may be an early key event of arsenic-induced liver injury. Silent mating type information regulation 2 homolog 1 (SIRT1)/ recombinant peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important pathway regulating mitochondrial mass and function. However, whether arsenic-induced liver injury is related to mitochondrial dysfunction mediated by SIRT1/PGC-1α pathway remains unclear. Objective To investigate potential effects of sodium arsenite (NaAsO2) on mitochondrial function and expressions of SIRT1/PGC-1α pathway-related proteins in human normal liver cell. Methods Human normal liver cells (MIHA cells) were used as the research object. MIHA cells were treated with different concentrations of NaAsO2 (0, 5, 10 and 20 μmol·L−1) for 24 h, and the cells were collected for study. The ultrastructure of mitochondria was observed by transmission electron microscopy, adenosine triphosphate (ATP) concentration by fluorescence method, mitochondrial membrane potential (MMP) level by flow cytometry, and SIRT1, PGC-1α and their downstream nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) protein expression levels by Western blotting. One-way analysis of variance and trend test were used for data statistical analysis. Results The viability of MIHA cells decreased gradually with the increase of NaAsO2 concentration (F=6495.47, P<0.001). The transmission electron microscope observation showed that the size of mitochondria in the 10 μmol·L−1 NaAsO2 treatment group was different, and the mitochondria were swollen or elongated in a rod-like shape. The mitochondria in the 20 μmol·L−1 NaAsO2 treatment group swelled like air spheres or vacuoles. The ATP concentration and MMP level of MIHA cells gradually decreased with the increase of NaAsO2 concentration (Ftrend of ATP=172.28, Ftrend of MMP=59.91, both Ps<0.001). Compared with the control group, the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM were not significantly changed in the 5 μmol·L−1 NaAsO2 treatment group, while the protein expression levels of SIRT1, PGC-1α, and TFAM were decreased in the 10 μmol·L−1 NaAsO2 treatment group, and the protein expression levels of SIRT1, PGC-1α, and NRF1 were decreased in the 20 μmol·L−1 NaAsO2 treatment group. The results of trend test showed that the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM decreased gradually with the increase of NaAsO2 concentration (Ftrend of SIRT1=47.07, P<0.001; Ftrend of PGC-1α=15.17, P<0.01; Ftrend of NRF1=13.54, P<0.01; F trend of TFAM=4.20, P<0.05). Conclusion The down-regulation of SIRT1/PGC-1α and its downstream NRF1 and TFAM may be involved in NaAsO2-induced mitochondrial dysfunction in liver cells.

Expression and diagnostic value of NKX3.1 and NKX2.2 in mesenchymal chondrosarcoma / 中华病理学杂志

Objective: To investigate the immunohistochemical expression of NKX3.1 and NKX2.2 in mesenchymal chondrosarcoma (MC), and to explore the differential diagnostic value of NKX3.1 and NKX2.2 in MC and other types of small round cell malignant tumors. Methods: A total of 12 cases of MC and 97 other small round cell malignant tumors diagnosed in Jinling Hospital, Nanjing University School of Medicine from 2001 to 2020 were collected for NKX3.1 and NKX2.2 immunohistochemical detection. Among them, two kinds of NKX3.1 antibodies [rabbit polyclonal antibody and rabbit monoclonal antibody (EP356)] were used for detection in 12 cases of MC, and one NKX3.1 antibody (rabbit polyclonal antibody) was detected in 97 cases of other small round cell malignant tumors, and the relevant literature was reviewed. Results: The 12 MC patients included 7 females and 5 males, with a mean age of 33 years (14-54 years). Nine cases were from bone and three from soft tissue. Among the 12 MC patients, 8 patients had postoperative recurrence or metastasis, and 3 of them died of tumor recurrence or metastasis. Histologically, 12 cases of MC showed typical bidirectional differentiation.The positive rate of both NKX3.1 antibodies in MC was 12/12, NKX3.1 was focal weakly positive in only one of 12 chondrosarcomas (grade 3), 5 alveolar rhabdomyosarcomas, 5 embryonal rhabdomyosarcomas, and 5 solitary fibrous tumors, respectively. The remaining 70 cases of other small round cell malignant tumors were negative. The positive rates of NKX2.2 in MC, Ewing sarcoma and olfactory neuroblastoma were 12/12, 15/15 and 4/5, respectively. In 12 cases of chondrosarcoma (grade 3), 5 cases of poorly differentiated synovial sarcoma, 5 cases of alveolar rhabdomyosarcoma, and 5 cases of solitary fibrous tumor, NKX2.2 was focally and weakly positive in only one case, respectively, and all the remaining 50 cases of other small round cell malignant tumors were negative. Conclusions: The expression of NKX3.1 and NKX2.2 proteins are significant indicators in the diagnosis of MC, and the combined detection of NKX3.1 and NKX2.2 can help distinguish MC from most other small round cell malignant tumors.

Research on the equity and spatial accessibility of oral medical resources in Wuhan / 公共卫生与预防医学

Objective To analyze the equity of the allocation of oral medical resources and the accessibility of health service capabilities in Wuhan. Methods The equity of oral medical resources was calculated with Gini coefficient and Theil index, accessibility was assessed by two-step floating catchment area model, and the spatial autocorrelation was used to study the high-low clustering of accessibility. Results The Gini coefficient of oral medical resources based on population level was around 0.3, and the Gini coefficient of oral medical resources based on geographic area was greater than 0.6. Theil index calculation results were similar. In terms of overall accessibility, the area with poor accessibility was 2,428 square kilometers, reaching 28.38% of the total area, while the area with better accessibility accounted for 14.18%. Conclusion The allocation of oral medical care resources based on population distribution was fairer and better than that based on geographic area. Moreover, the geographical accessibility varies greatly between regions, showing the characteristics of high-high cluster and low-low cluster.

Timing of surgical ligation of patent ductus arteriosus in very low birth weight infants / 中国当代儿科杂志

OBJECTIVES@#To study the effect of timing of surgical ligation of patent ductus arteriosus (PDA) on the prognosis of very low birth weight infants (VLBWI).@*METHODS@#The medical data of VLBWI who underwent transthoracic ligation for PDA from June 2018 to May 2021 were reviewed retrospectively. The infants were divided into early ligation group (≤21 days of age) and late ligation group (>21 days of age) based on the age of ligation. The two groups were compared in terms of perioperative clinical features, complications, and mortality. The risk factors for early surgical ligation were analyzed.@*RESULTS@#A total of 72 VLBWI were enrolled, with 19 infants (26%) in the early ligation group and 53 infants (74%) in the late ligation group. There were significant differences in birth weight, gestational age, weight at operation, days of age at operation, rates of preoperative invasive and noninvasive mechanical ventilation, incidence rate of pulmonary hemorrhage, incidence rate of hypotension, preoperative PDA internal diameter (mm/kg), intraoperative PDA external diameter (mm/kg), incidence rate of post-ligation cardiac syndrome, and duration of postoperative invasive mechanical ventilation between the two groups (P<0.05). A binary logistic regression analysis showed that pulmonary hemorrhage was an indication of early surgical ligation of PDA (P<0.05). There were no significant differences in the incidence rates of post-operative complications and the mortality rate between the early ligation and late ligation groups.@*CONCLUSIONS@#Early surgical ligation may be performed for VLBWI who are experiencing pulmonary hemorrhage and hemodynamically significant PDA confirmed by cardiac ultrasound after birth. However, post-ligation cardiac syndrome should attract enough attention. In addition, early surgical ligation of PDA does not increase the risk of surgery-related and long-term complications or death, indicating that it is a safe and feasible treatment option.

Value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight infants / 中国当代儿科杂志

OBJECTIVES@#To study the value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight (VLBW) infants.@*METHODS@#A retrospective analysis was performed for 51 VLBW infants who were admitted from March 2020 to June 2021, with an age of ≤3 days and a length of hospital stay of ≥14 days. According to the diameter of patent ductus arteriosus (PDA) on days 14 and 28 after birth, the infants were divided into three groups: large PDA group (PDA diameter ≥2 mm), small PDA group (PDA diameter <2 mm), and PDA closure group (PDA diameter =0 mm). The echocardiographic parameters measured at 72 hours after birth were compared among the three groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of the echocardiographic parameters in predicting persistent patency of the ductus arteriosus (PDA≥2 mm) at the ages of 14 and 28 days.@*RESULTS@#On day 14 after birth, there were 17 infants in the large PDA group, 11 in the small PDA group, and 23 in the PDA closure group. On day 28 after birth, there were 14 infants in the large PDA group, 9 in the small PDA group, and 26 in the PDA closure group. There were significant differences in gestational age, birth weight, rate of pulmonary surfactant use, and incidence rate of hypotension among the three groups (P<0.05). PDA diameter, end-diastolic velocity of the left pulmonary artery, left ventricular output, and left ventricular output/superior vena cava flow ratio measured at 72 hours after birth were associated with persistent patency of the ductus arteriosus at the ages of 14 and 28 days (P<0.05), and the ratio of the left atrium to aorta diameter was associated with persistent patency of the ductus arteriosus at the age of 28 days (P<0.05). The ROC curve analysis showed that the area under the curve that the PDA diameter measured at 72 hours after birth predicting the persistent patency of the ductus arteriosus at the ages of 14 and 28 days was the largest (0.841 and 0.927 respectively), followed by end-diastolic velocity of the left pulmonary artery, with the area under the curve of 0.793 and 0.833 respectively.@*CONCLUSIONS@#The indicators obtained by beside echocardiography at 72 hours after birth, especially PDA diameter and end-diastolic velocity of the left pulmonary artery, can predict persistent patency of the ductus arteriosus at the ages of 14 and 28 days in VLBW infants, which provides a basis for the implementation of early targeted treatment strategy for PDA.

Status quo and development recommendations for infectious disease early warning system in public general hospitals in China / 中华医院管理杂志

Early warning of infectious disease outbreak is key to controlling epidemics. Public general hospitals can effectively play their " outpost" role in the early warning and response of infectious diseases, which is directly related to the success of epidemic prevention and control. The authors summarized the current construction and main functions of infectious disease early warning systems at national level, regional level and public general hospitals, analyzed the problems existing in such construction, and put forward targeted suggestions. As found by the authors, some public general hospitals in China have initially built an early warning system for infectious diseases, achieving early recognition, early warning and reporting of infectious diseases to some extent. However, these systems were challenged by such shortcomings as insufficient intelligence, lack of data information exchange, immature practice and application, and lack of attention to the monitoring and early warning of endemic infectious diseases. It is suggested to improve the policy and system support in the future, to expand the types of infectious diseases for monitoring and early warning, to enlarge the sources of monitoring data and to strength hospital informationization construction.

The mechanisms of mitochondrial dysfunction caused by pathogenic genes of Parkinson′s disease / 中华神经科杂志

Parkinson′s disease (PD) is a complex neurodegenerative disorder typically known for characteristic loss of dopaminergic neurons in the substantia nigra striatum. To date, therapeutic approaches for PD are still lacking due to the multifactorial etiology and complicated pathogenesis. Thus, the studies relative to the biological mechanisms and drug development of PD are the hotspot in this field. In recent years, numerous studies suggest that the PD is associated with mitochondrial dysfunction which is affected by multiple genes regulation. Genome-wide association studies have proved that monogenic PD gene locus is associated with mitochondrial dysfunction. Although there are many studies on how PD pathogenic genes regulate mitochondrial dysfunction then affect neuronal physiological function and ultimately lead to the PD, the effects of mutations in PD-associated genes on mitochondrial dysfunction remain not fully understood. In this review, the literature discussing the mechanisms of mitochondrial dysfunction in the context of PD was summarized with the aim to implicate the potential opportunities for therapeutically targeting mitochondria.

Effects of Sedimentary Type Limonitum on 6-keto-PGF1α，TXB2 and Other Related Indexes and Metal Ions in Blood of Warfarin Hemorrhage Model Rats / 中国实验方剂学杂志

Objective:To study the effect of sedimentary type Limonitum on hemostatic indexes in blood and metal ions in serum of rats with hemorrhage. Method:The hemorrhagic rat models were established by warfarin sodium. The experimental animals were divided into control group，model group，powder group and water decoction group. On day 15 from drug administration， the contents of 6-keto prostaglandin F₁<italic>_α</italic>（6-keto-PGF₁<italic>_α</italic>），thromboxane B₂（TXB₂），arachidonic acid（AA），endothelin 1（ET-1），platelet activating factor（PAF），P-selectin（PS），and Ca²⁺ in the whole blood of rats in each group were determined by enzyme-linked immunosorbent assay（ELISA）. The contents of Na，Mg，K，Ca，Fe，Al，Li，Be，Ti，V，Cr，Mn，Co，Ni，Cu，Zn，As，Sr，Cd，Sn，Sb，Ba，and Pb in serum samples were determined by inductively coupled plasma optical emission spectrometer（ICP-OES） and inductively coupled plasma mass spectrometry（ICP-MS）. Result:Compared with the model group，the content of 6-keto-PGF₁<italic>_α</italic> was reduced in the powder group and water decoction group （<italic>P</italic><0.05），and the contents of TXB₂，AA，ET-1，PAF，PS，Ca²⁺weresignificantly increased（<italic>P</italic><0.01），with a positive and beneficial regulatory effect. In the powder group， 10 kinds of metal elements in serum of rats were significantly and positively regulated： Na，K，Ca，Fe，Li，Ti，V，Co，Cu，and Zn（<italic>P</italic><0.05，<italic>P</italic><0.01）. In the water decoction group， 10 metal elements with significant positive regulation were as follows： Na，K，Ca，Fe，Li，V，Ni，Cu，Zn，and Sr（<italic>P</italic><0.05，<italic>P</italic><0.01）. In addition，the content of Cr（<italic>P</italic><0.01） in the powder group and Cr（<italic>P</italic><0.01），Pb（<italic>P</italic><0.05） in the water decoction group were significantly reduced. Conclusion:The powder and water decoction of sedimentary type Limonitum had definite and positive intervention effect on warfarin hemorrhage model rats，which could play a coagulation role by enhancing the vasoconstriction ability，promoting the activation of platelets，and increasing the platelet aggregation rate and blood viscosity. The metal elements such as Na，K，Ca，Fe，Li，Ti，V，Co，Cu，Zn，Ni and Sr may be the material basis for sedimentary type Limonitum to exert hemostatic effect. According to the above indicators，the intervention effect of powder group and decoction group was basically the same.

Metabolomics Analysis of Chloriti Lapis on Brain Tissue of PTZ-kindled Epileptic Rats / 中国实验方剂学杂志

Objective:To explore the possible mechanism of Chloriti Lapis in the treatment of epilepsy by the metabonomics of brain tissue in pentylenetetrazol （PTZ）-kindled epileptic rats treated with Chloriti Lapis. Method:The epileptic animal model in rats was established by PTZ kindling， and the rats were divided into the control group， model group， carbamazepine group and Chloriti Lapis group. The brain tissue samples were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry（UPLC/Q-TOF-MS）， and the experimental results were statistically analyzed by partial least squares-discriminant analysis （PLS-DA） and SPSS 18.0. Result:The metabolic fingerprints and metabolic profiles of the rat brain tissue were established， which showed that the metabolic profiles of each group had changed significantly and could be separated well among the groups. Moreover， the Chloriti Lapis group had a tendency to be closer to the control group than the carbamazepine group. Seven differential metabolites were screened， including phosphatidylserine （PS） （18∶0/18∶0）， <italic>L</italic>-glutamic acid， docosahexaenoyl ethanolamide， arachidonic acid， glucosylsphingosine， cholestane-3，7，12，24，25-pentol and lysophosphatidylcholine （LysoPC） （P-18∶0）. Except for docosahexaenoyl ethanolamide and LysoPC （P-18∶0）， Chloriti Lapis had significant intervening and regulating effects on the other five differential metabolites. There were 12 possible metabolic pathways that affected the metabolic disorder of PTZ-kindled rats， and 3 important metabolic pathways （pathway impact>0.1）， namely， <italic>D-</italic>glutamine and <italic>D-</italic>glutamate metabolism， alanine， aspartate and glutamate metabolism， and arachidonic acid metabolism， among which <italic>D-</italic>glutamine and <italic>D-</italic>glutamate metabolism was the most important metabolic pathways. Conclusion:From this point of view， Chloriti Lapis has a clear intervention effect on PTZ-kindled epileptic rats， which may be related to the intervention of the above differential metabolite contents and related metabolic pathways. It can reduce the toxic effect of excitatory neurotransmitters on neurons in brain tissue and inhibit the development of inflammation in brain tissue， so as to maintain the biological function of brain cells and slow down the occurrence of epilepsy.

Progress in the research of application of hot springs in health care and adjuvant treatment of diseases / 上海预防医学

Hot spring is a kind of precious natural water resource formed under specific geological conditions and obtained by natural gushing or artificial drilling, and is rich in minerals and trace elements peculiar to deep strata. Hot spring bathing is a physical therapy with a long history. An increasing number of studies have shown the positive effects of hot spring bathing in maintaining health and the auxiliary treatment and rehabilitation of chronic diseases. This paper reviews the distribution, classification and application history of hot springs, and further explores the research on the effect of hot springs on the improvement of sub-health status and the adjuvant treatment of chronic diseases such as skin diseases, cardiovascular diseases and joint diseases, so as to provide reference for further understanding of the physiotherapy value of hot spring bathing and boost its role in the development of big health industries.

Effects of intervention of hot spring bathing on antioxidation functions in population / 上海预防医学

Objective To understand the influence of hot spring bathing intervention on population's antioxidation functions. Methods Three typical types of hot spring(metasilicic acid type, warm mineral type and temperature type)in Guizhou Province were selected for investigation. According to the inclusion-exclusion criteria, questionnaires and physical examinations results, 421 individuals were selected as observation subjects for hot spring bathing intervention, of which 311 subjects completed 40 to 50 minutes of intervention once a day, 5 days a week, and for 4 weeks. Two physical examinations before and after the intervention were conducted for the 311 subjects. The fasting venous blood samples on the mornings of two physical examinations were collected and the serum was separated. Levels of serum oxidative stress-related parameters including total superoxide dismutase(T-SOD), copper zinc superoxide dismutase(Cu-Zn SOD), glutathione sulfur transferases(GSTs)glutathione peroxidase(GSH-px), sulfhydryl(-SH)and malondialdehyde(MDA)were measured by enzymatical methods. Results The overall comparison showed that compared with before the bathing intervention, the levels of antioxidant enzymes including T-SOD, Cu-Zn SOD, GSTs and GSH-px significantly increased in serum after the intervention(all P < 0.05). There was an increasing trend of serum -SH level after the intervention, but with no statistical differences were seen(P > 0.05). MDA, a product of lipid peroxidation, significantly decreased in serum after the intervention(P < 0.05). The results of classified comparison showed that the effects of different hot spring types on antioxidant enzymes were different. Metasilicic acid type significantly increased the activities of GSTs and GSH-px in serum(all P < 0.05), warm mineral type significantly increased the activities of T-SOD and Cu-Zn SOD in serum(all P < 0.05), and temperature type significantly increased the activities of T-SOD, Cu-Zn SOD and GSTs in serum(all P < 0.05). There were increasing trends of serum -SH levels after bathing intervention of all three hot spring types, but no statistical differences were seen(all P > 0.05). The serum MDA levels decreased significantly after bathing intervention of all three types of hot springs(all P < 0.05). Conclusion Overall, bathing intervention of hot springs can improve the activities of antioxidant enzymes and reduce lipid peroxidation products in population. The results of oxidative stress parameters are slightly different in different types of hot springs. The subjects mainly show the elevation of glutathione related enzyme(GSTs and GSH-px)activities after intervention of metasilicic acid type, the elevation of superoxide dismutase(SOD)activities after intervention of warm mineral type and temperature type, and the decline of lipid peroxidation levels after intervention of all three types. It suggests that hot spring bathing may have certain effects on improving the body's antioxidation functions.

Effect of hot spring bathing on rheumatoid related indicators and joint pain / 上海预防医学

Objective To observe the intervention effect of typical hot spring bathing in Guizhou province on joint pain, serum anti-keratin antibody(AKA), anti-perinuclear factor antibody(APF)and anti-cyclic citrullinated peptide antibody(CCP). Methods A total of 160 people with joint pain symptoms from five typical hot spring areas in Guizhou province were selected as the subjects. They were treated with hot spring bathing intervention for 4 weeks, once a day, 5 times a week, 40 to 50 minutes each time. According to the evaluation index of physiotherapy natural mineral water in the Code for Geological Exploration and Evaluation of Natural Warm Mineral Water Resources(GB/T 13727-2016)and geological types, the five typical hot springs were divided into three different types, namely water temperature type hot springs(water temperature > 36 ℃), metasilicate type hot springs(metasilicate > 50 mg/L)and warm mineral spring type hot springs(total dissolved solids > 1 000 mg/L). WHO pain grading standard was used to score the degree of joint pain before and after hot spring bathing intervention. Serum APF, AKA and CCP antibodies were detected by ELISA kit before and after hot spring bathing. Results The joint pain score of the subjects was 2.60±0.60, and the joint pain score of the total population decreased after intervention(0.61±0.57, P < 0.05). Before intervention, the joint pain scores of water temperature type, metasilicic acid type and warm mineral spring type were 2.78±0.96, 1.98±1.15 and 3.31±0.57, respectively. After intervention, the scores of joint pain of the three kinds of hot spring bathing patients all decreased(P < 0.05), and were 0.50±0.65, 0.48±0.74 and 0.85±0.90, respectively. Before intervention, AKA(ng/L)and CCP(μg/mL)antibody levels of the observed subjects were 34.89±16.06 and 107.58±10.40, respectively, which significantly decreased after intervention(both P < 0.05), namely 26.06±10.68 and 102.93±6.01, respectively. AKA(ng/L)was 35.04±20.01 before intervention, but decreased significantly after intervention(26.61±7.54, P < 0.05). AKA(ng/L)and CCP(μg/mL)were 31.09±17.26 and 106.51±10.13 before intervention, respectively. After intervention, the above two antibody indexes significantly decreased(all P < 0.05)to 24.53±13.98 and 98.57±5.68, respectively. Before intervention, the AKA(ng/L), APF(ng/mL)and CCP(μg/mL)antibody levels were 38.40±8.66, 349.46±118.43 and 104.96±9.66, respectively. After intervention, the above three antibody indexes significantly decreased(all P < 0.05). The values were 34.00±7.55, 269.38±127.55 and 101.65±3.04, respectively. Conclusion The typical hot spring bathing intervention in Guizhou province can relieve the symptoms of joint pain, and the three types of hot springs can reduce the levels of AKA, APF and CCP antibodies to different degrees, and the warm mineral spring type of hot spring is better than the other types of hot spring.

Analysis of the effect of hot spring bathing on serum melatonin levels and its association with sleep and anxiety / 上海预防医学

Objective To explore the improvement effect of typical hot spring bathing on sleep and anxiety and its correlation with serum melatonin level in Guizhou province. Methods Five typical characteristic hot springs in Guizhou were selected according to the geological type of hot spring water. A total of 226 residents in these areas were selected for the survey and the self-rating scale of sleep(SRSS)and the self-rating anxiety scale(SAS)were used to measure their scores before and after hot spring bathing, and the correlation between the changes of SRSS and SAS scores and the serum melatonin levels were analyzed. Results The SRSS and SAS scores of the respondents after hot spring bathing were lower than before, and the difference was statistically significant(P < 0.05). Serum melatonin levels after hot spring bathing were significantly higher than before(P < 0.05), and there was a negative correlation between the changes of SRSS and SAS scores and serum melatonin levels(P < 0.05). Conclusion Typical hot springs in Guizhou Province can significantly improve the sleep quality and anxiety state, which are related to the elevation of serum melatonin level.

Study on the effect of hot spring bath therapy on sleep quality based on health bracelets / 上海预防医学

Objective To study the relieving effects of hot spring bath therapy on sleep quality for people with sleep disorders based on data from health bracelets. Methods After health examinations, 311 people with sleep disorders who participated in the bath therapy in five typical hot spring areas in Guizhou Province were selected as the subjects. A four-week hot spring bath therapy was implemented, and the bathing method and the classification of hot springs were the same as the"Overview of study of the physiotherapy efficacy of typical hot springs in Guizhou Province". The daily sleep time at night(minutes), deep sleep ratio(%), light sleep ratio(%)and rapid eye movement ratio(%)for all subjects were collected using the Huawei Honor Band 3 health bracelets. Repeated measures analysis of variance was used to compare the differences in sleep quality indicators of each group at night each week. The effect of three different hot spring bath therapies on the improvement of night sleep quality was evaluated by factor analysis. Results Hot spring bath therapy can increase night sleep time and deep sleep ratio, while reducing light sleep ratio. Compared with the first week, the night sleep time in the following three weeks significantly increased(P < 0.05), especially in the fourth week; the deep sleep ratio during the third and fourth weeks was significantly higher than during the first and second weeks(P < 0.05), but the light sleep ratio was lower than during the first and second weeks(P < 0.05). The rapid eye movement ratio did not change significantly throughout the 4 weeks(P > 0.05). Further classified according to the physiotherapy components of geological hot springs, the results showed that the water temperature type of hot springs can increase night sleep time and reduce light sleep ratio; the warm mineral type of hot springs has a certain regulatory effect on increasing night sleep time, deep sleep ratio and reducing light sleep ratio; the metasilicic acid type of hot springs can improve night sleep quality by increasing night sleep time and deep sleep ratio, while reducing light sleep ratio and rapid eye movement ratio. The factor analysis results suggest that the metasilicic acid type of hot springs is better than the water temperature type and warm mineral type of hot springs in improving night sleep quality. Conclusion Hot spring bath therapy can improve the night sleep quality for people with sleep disorders to varying degrees, and the metasilicic acid type of hot springs is relatively better than other types.

Ameliorative effect of hot spring bathing on the elevation of blood lipid in population / 上海预防医学

Objective To explore the effect of typical hot spring bathing of Guizhou Province on dyslipidemia, which could provide scientific basis for clarifying the physiotherapy effect of hot springs. Methods The typical hot spring sites of three main types(hydrothermal hot spring, warm mineral hot spring and metasilicate hot spring)in Guizhou Province were selected as investigation sites. 189 residents with hyperlipidemia near the investigation sites were selected as subjects and were treated with hot spring baths for 4 weeks, once a day, 5 times a week and 40-50 minutes each time. The age and gender distribution of the subjects were obtained by a questionnaire. The levels of TC, TG, LDL-C and HDL-C in serum were measured by automatic biochemical analyzer at baseline and at the end of hot spring baths. The differences of the three kinds of hot spring baths on improvement rate of dyslipidemia, the changes of abnormal blood lipid indexes and their improvement rates were compared. Results After baths of hydrothermal hot springs, warm mineral hot springs and metasilicate hot springs, the improvement rates of abnormally elevated lipids were 15.6%, 40.4% and 47.9%, respectively. The improvement rates of abnormally elevated lipids after baths of warm mineral hot springs and metasilicate hot springs were significantly higher than that after hydrothermal spring baths(all P < 0.05). Compared with before hot spring bathing, the levels of TC, TG, LDL-C and non-HDL-C in serum significantly decreased in all three kinds of hot springs. Moreover, the degree of decrease of TG in serum and the improvement rate of abnormal TG after baths of warm mineral spring and metasilicate hot spring were significantly higher than that after hydrothermal spring baths. The degree of decrease of LDL-C in serum and the improvement rate of abnormal LDL-C after baths of metasilicate hot spring were significantly higher than that after baths of hydrothermal spring and warm mineral spring(all P < 0.05). Conclusion The three types of typical hot spring baths in Guizhou Province can mitigate the elevation of blood lipid. Compared with hydrothermal spring, warm mineral spring and metasilicate hot spring may have better improvement effect on blood lipid elevation due to their more significant improvement effect on abnormal elevation of TG and LDL-C in serum.