Spatio-temporal disparities of Clonorchis sinensis infection in animal hosts in China: a systematic review and meta-analysis.

BACKGROUND: Clonorchis sinensis, one of the most important food-borne zoonotic trematodes, remains prevalent in China. Understanding its infection status in animals is crucial for controlling human clonorchiasis. Here we conducted a systematic review and meta-analysis to focus on the spatio-temporal disparities of C. sinensis infection in animals in China. METHODS: Data on C. sinensis prevalence in snails, the second intermediate hosts, or animal reservoirs in China were extracted from electronic databases including PubMed, Embase, Web of Science, Chinese Wanfang database, CNKI, VIP, and China Biomedical Literature database. A random-effects meta-analysis model was utilized to estimate the pooled prevalence in each of the above animal hosts. Subgroup analysis and multivariable meta-regression were performed to explore potential sources of heterogeneity across studies and compare the temporal disparity of infection rates between high and low epidemic areas. Scatter plots were used to depict the biogeographical characteristics of regions reporting C. sinensis infection in animals. RESULTS: The overall pooled prevalence of C. sinensis was 0.9% (95% CI: 0.6-1.2%) in snails, 14.2% (12.7-15.7%) in the second intermediate host, and 14.3% (11.4-17.6%) in animal reservoirs. Prevalence in low epidemic areas (with human prevalence < 1%) decreased from 0.6% (0.2-1.2%) before 1990 to 0.0% (0.0-3.6%) after 2010 in snails (P = 0.0499), from 20.3% (15.6-25.3%) to 8.8% (5.6-12.6%) in the second intermediate hosts (P = 0.0002), and from 18.3% (12.7-24.7%) to 4.7% (1.0-10.4%) in animal reservoirs. However, no similar decrease in prevalence was observed in high epidemic areas (with human prevalence ≥ 1.0%). C. sinensis infections were predominantly reported in areas with altitudes below 2346 m and annual cumulative precipitation above 345 mm and were mostly concentrated in eastern China. CONCLUSIONS: There are spatio-temporal disparities in the animal infections of C. sinensis in different areas of China. Animal infections are primarily concentrated in regions with low altitude and high precipitation. The results suggest that implementing One Health-based comprehensive measures targeting both humans and animals, especially in high epidemic areas, is essential for successful eradication of C. sinensis in China.

LRRK2 G2019S and Parkinson's disease: insight from Neuroinflammation.

The multiple hypothesis holds that the pathogenesis of Parkinson's disease (PD) requires many factors such as heredity, environment and ageing. Mutations in Leucine-rich repeat kinase 2 (LRRK2) are recognized the risk factors of PD, and closely related to sporadic and familial PD and can regulate a variety of cellular pathways and processes. An Increasing number of studies has shown that glial hyperactivation-mediated neuroinflammation participates in dopaminergic neuron degeneration and pathogenesis of PD. LRRK2 is essential to the regulaton of chronic inflammation, especially for the central nervous system. The review spotlights on the novel development of LRRK2 on microglia and astrocytes, and explore their potential therapeutic targets, in order to provide a new insights in PD. Key messages: What is already known on this topic The G2019S mutation of LRRK2 is now recognised as a pathogenic mutation in PD. Previous studies have focused on the relationship between neurons and LRRK2 G2019S. What this study adds Neuroinflammation mediated by LRRK2 G2019S of glial cells affects the progress and development of PD and attention must be paid to the role of LRRK2 G2019S in glial cells in PD. How this study might affect research, practice or policy Developing anti-inflammatory drugs from the perspective of LRRK2 G2019S of glial cells is a new direction for the treatment of PD.

Serum glial cell line-derived neurotrophic factor (GDNF) a potential biomarker of executive function in Parkinson's disease.

Objective: Evidence shows that the impairment of executive function (EF) is mainly attributed to the degeneration of frontal-striatal dopamine pathway. Glial cell line-derived neurotrophic factor (GDNF), as the strongest protective neurotrophic factor for dopaminergic neurons (DANs), may play a role in EF to some extent. This study mainly explored the correlation between serum GDNF concentration and EF performance in Parkinson's disease (PD). Methods: This study recruited 45 healthy volunteers (health control, HC) and 105 PD patients, including 44 with mild cognitive impairment (PD-MCI), 20 with dementia (PD-D), and 20 with normal cognitive function (PD-N). Neuropsychological tests were performed to evaluate EF (working memory, inhibitory control, and cognitive flexibility), attention, language, memory, and visuospatial function. All subjects were tested for serum GDNF and homovanillic acid (HVA) levels by ELISA and LC-ESI-MS/MS, respectively. Results: PD-MCI patients showed impairments in the trail making test (TMT) A (TMT-A), TMT-B, clock drawing test (CDT) and semantic fluency test (SFT), whereas PD-D patients performed worse in most EF tests. With the deterioration of cognitive function, the concentration of serum GDNF and HVA in PD patients decreased. In the PD group, the serum GDNF and HVA levels were negatively correlated with TMT-A (r GDNF = -0.304, P < 0.01; r HVA = -0.334, P < 0.01) and TMT-B (r GDNF = -0.329, P < 0.01; r HVA = -0.323, P < 0.01) scores. Serum GDNF levels were positively correlated with auditory verbal learning test (AVLT-H) (r = 0.252, P < 0.05) and SFT (r = 0.275, P < 0.05) scores. Serum HVA levels showed a positively correlation with digit span test (DST) (r = 0.277, P < 0.01) scores. Stepwise linear regression analysis suggested that serum GDNF and HVA concentrations and UPDRS-III were the influence factors of TMT-A and TMT-B performances in PD patients. Conclusion: The decrease of serum GDNF concentration in PD patients was associated with impaired inhibitory control, cognitive flexibility, and attention performances. The changes of GDNF and HVA might synergistically participate in the occurrence and development of executive dysfunction in PD patients.

Nucleic Acid Prevalence of Zoonotic Babesia in Humans, Animals and Questing Ticks, a Systematic Review and Meta-Analysis.

Background: Zoonotic Babesia infections are an emerging public health threat globally. The geographical distribution, animal reservoirs and tick vectors vary greatly across Babesia species, and estimations of prevalence reported in works within the literature are also quite different. Better prevalence estimates and identification of moderators are needed to understand the global transmission risk of different zoonotic Babesia species, and to provide crucial background information for the diagnosis, treatment and control of zoonotic babesiosis. Methods: We conducted a systematic review and meta-analysis to determine the global nucleic acid prevalence of different zoonotic Babesia species in humans, animals and ticks. Relevant publications were obtained from several electronic databases and grey literature up to December 2021. Articles were included if they were published in English or Chinese and reported the nucleic acid prevalence of zoonotic Babesia species in humans, animals or ticks. The pooled estimates of prevalence were determined using a random effect model. Heterogeneity was investigated using subgroup analyses and random effect meta-regression models. Results: Of 3205 unique studies, 28 were included by the systematic review of zoonotic Babesia for humans, 79 for animals and 104 for ticks. The results showed overall pooled estimates of nucleic acid prevalence for the following: B. microti-1.93% (0.32-4.69%) in humans; B. microti-7.80% (5.25-10.77%), B. divergens-2.12% (0.73-4.08%) and B. venatorum-1.42% (0.30-3.16%) in animals; and B. microti-2.30% (1.59-3.13%), B. divergens-0.16% (0.05-0.32%), and B. venatorum-0.39% (0.26-0.54%) in questing ticks. The type of population, animal reservoir or tick vector, detecting method and continent were moderators possibly associated with heterogeneity, yet the remaining heterogeneity that was not explained was still substantial (all QE p values < 0.05). Conclusions:B. microti is the most prevalent and widely distributed zoonotic Babesia species globally. The wide range of suitable animal reservoirs and potential transmission vectors and high prevalence in animals and ticks may contribute to the worldwide distribution of B. microti. Other zoonotic Babesia species were relatively less prevalent and were reported in quite limited areas.

Application of Neurotoxin-Induced Animal Models in the Study of Parkinson's Disease-Related Depression: Profile and Proposal.

Depression can be a non-motor symptom, a risk factor, and even a co-morbidity of Parkinson's disease (PD). In either case, depression seriously affects the quality of life of PD patients. Unfortunately, at present, a large number of clinical and basic studies focused on the pathophysiological mechanism of PD and the prevention and treatment of motor symptoms. Although there has been increasing attention to PD-related depression, it is difficult to achieve early detection and early intervention, because the clinical guidelines mostly refer to depression developed after or accompanied by motor impairments. Why is there such a dilemma? This is because there has been no suitable preclinical animal model for studying the relationship between depression and PD, and the assessment of depressive behavior in PD preclinical models is as well a very challenging task since it is not free from the confounding from the motor impairment. As a common method to simulate PD symptoms, neurotoxin-induced PD models have been widely used. Studies have found that neurotoxin-induced PD model animals could exhibit depression-like behaviors, which sometimes manifested earlier than motor impairments. Therefore, there have been attempts to establish the PD-related depression model by neurotoxin induction. However, due to a lack of unified protocol, the reported results were diverse. For the purpose of further promoting the improvement and optimization of the animal models and the study of PD-related depression, we reviewed the establishment and evaluation strategies of the current animal models of PD-related depression based on both the existing literature and our own research experience, and discussed the possible mechanism and interventions, in order to provide a reference for future research in this area.

The cognitive impairment and risk factors of the older people living in high fluorosis areas: DKK1 need attention.

OBJECTIVE: To evaluate cognitive impairment and risk factors of elders in high fluoride drinking water areas and investigate whether DKK1 is involved in this disorder. METHODS: MoCA-B and AD-8 were used to measure the cognitive functions of 272 and 172 subjects over the age of 60 came from the high and normal fluoride drinking water areas respectively, general information and peripheral blood were collected, the level of SOD, GSH and MDA were measured, mRNA level of DKK1, the concentration of blood fluoride and the polymorphism of APOE were tested. RESULTS: The blood fluoride concentration, mRNA level of DKK1 and ratio of abnormal cognitive function of subjects in high fluorine drinking water areas were higher than those in normal areas. The level of SOD of subjects in high fluorine drinking water was low compared with those in normal areas. The level of MDA and GSH had no difference between the two crowds in different fluorine drinking water areas. There were differences in cigarette smoking, education, dental status, hypertension, hyperlipidaemia and APOE results between the two crowds in different fluorine drinking water areas. The mRNA level of DKK1 and the level of cognitive function showed a positive correlation and DKK1 was one of five risk factors involved in cognitive impairment of older people living in high fluorosis areas. CONCLUSIONS: The cognitive functions could be impaired in the older people living in high fluoride drinking water areas, and DKK1 may as a potential intervention point of this brain damage process need attention.

Serotonin 2 Receptors, Agomelatine, and Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease.

There are nearly 50 million Alzheimer's disease (AD) patients worldwide, 90% of whom develop behavioral and psychological symptoms of dementia (BPSD), which increase the mortality rate of patients, and impose an economic and care burden on families and society. As a neurotransmitter and neuromodulator, serotonin is involved in the regulation of psychoemotional, sleep, and feeding functions. Accumulating data support the importance of serotonin in the occurrence and development of BPSD. Studies have shown that reduction of serotonin receptors can increase depression and mental symptoms in AD patients. At present, there is no drug treatment for AD approved by the US Food and Drug Administration. Among them, agomelatine, as a new type of antidepressant, can act on serotonin 2 receptors to improve symptoms such as depression and anxiety. At present, research on BPSD is still in the preliminary exploratory stage, and there are still a lot of unknowns. This review summarizes the relationship between serotonin 2 receptors, agomelatine, and BPSD. It provides a new idea for the study of the pathogenesis and treatment of BPSD.

A mobile terminal application program was used for endotracheal tube cuff pressure measurement.

We studied the application of a mobile terminal application program in endotracheal tube (ETT) cuff pressure measurement to improve the implementation rate of scientific ETT cuff pressure measurement and to ensure that the pressure falls within the recommended range. A pre-post controlled study lasting for 18 months was undertaken in a 40-bed general intensive care unit (GICU). This included a 6-month baseline period (baseline group) and a 6-month intervention period (intervention group). The mobile terminal application program was applied to monitor the cuff pressure of endotracheal intubation as an intervention measure during the intervention period. ETT pressure was the main outcome measure, while gender, age, causes for ICU admission, sedation score, duration of prior intubation, size of ETT, and number of VAP patients were secondary outcomes. ETT cuff pressure was monitored 742 times in both the baseline group and the intervention group. A total of 56.9% of the cuff pressure measurements in the baseline group were within the recommended range, while 78.4% of measurements in the intervention group were within the recommended range, reflecting a statistically significant difference (P < 0.05). The application of the mobile terminal application program used for ETT cuff pressure measurement could improve the percentage of ETT cuff pressure measurements falling within the recommended range.

Effect of a 12-Week Aerobic Exercise Training on Serum Fetuin-A and Adipocytokine Levels in Type 2 Diabetes.

OBJECTIVE: We aimed to evaluate the effect of 12-week aerobic exercise training on fetuin-A levels in type 2 diabetes mellitus and examine the relationships between fetuin-A and adipocytokine levels and cardiovascular risk factors. METHODS: The study included 32 patients with type 2 diabetes mellitus who were assigned to an exercise or a control group. The exercise group underwent 12 weeks of exercise (consisting of a 5-min warm-up, 60-min aerobic bicycle training performed at 70% of the maximal heart rate, a cool-down period, 5 times/week). Adiponectin, resistin, and fetuin-A serum levels were measured using enzyme-linked immunosorbent assay. Leptin serum levels were measured by a radioimmunoassay. RESULTS: Exercise for 12 weeks significantly reduced serum fetuin-A (643.1±109.4 to 448.7±92.5 µg/mL, P<0.05), leptin (11.9±7.2 to 8.6±5.7 ng/dL, P<0.05), and resistin (3.2±1.5 to 2.2±1.4 ng/mL, P<0.05) levels, but increased adiponectin (6.9±1.9 to 8.1±1.7 µg/mL, P<0.05) levels. In the exercise group, Δfetuin-A positively correlated with differences in weight (r=0.654, P=0.046), body mass index (r=0.725, P=0.002), waist circumference (r=0.898, P=0.013), and adiponectin levels (r=0.662, P=0.035). CONCLUSIONS: Aerobic exercise significantly decreased serum fetuin-A levels in type 2 diabetes mellitus, which can be attributed to weight loss and related to increased adiponectin levels.

[Clinical application evaluation and revision suggestions of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for acute pharyngitis].

The purpose of this study is to analyze the obstructive factors of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for acute pharyngitis, and summarize the revision suggestions for follow-up revision and promotion. Clinical physicians from 181 hospitals in 27 regions of China were selected to complete the online questionnaire survey for statistical analysis of obstructive factors. We collected 501 copies of the applicability evaluation questionnaire and 503 copies of the application evaluation questionnaire. The obstructive factors mainly focused on limitation of the Guideline, inconvenience of access, particularity of primary medical structure and uneven distribution of surveyed subjects. As for amendments, it was suggested to improve the syndrome differentiation, indications, prescriptions, and add characteristic TCM therapies in Chinese medicine; it was suggested to clarify the time to use antibiotics in Western medicine. According to the results of this study, the relevant contents of the Guideline should be further improved so as to be better applied in clinical practice.

[Advantages and problems of traditional Chinese medicine in treatment of acute pharyngitis].

This paper systematically studies relevant literatures at home and abroad in recent years. China National Knowledge Internet (CNKI) was used to collect the literatures for acute pharyngitis treated with traditional Chinese medicine from January 1, 2006, to December 31, 2016, and the bibliometric method was employed for statistical analysis. A total of 493 papers were preliminarily selected. According to the inclusion criteria and exclusion criteria, 182 eligible articles were selected. According to the evaluation and analysis of the literatures, the Guidelines for Clinical Research of New Drugs is currently used as the common standards for the diagnosis and treatment of acute pharyngitis; Chinese patent medicines are the main traditional Chinese medicine for treating this disease; Decoctions for treatment of this disease include Lonicerae Japonicae Flos, Scutellariae Radix, Platycodonis Radix, Forsythiae Fructus, Glycyrrhizae Radix et Rhizoma, Scrophdlariae Radix, Isatidis Radix, and Ophiopogonis Radix; The bloodletting puncture is the common external therapy. Traditional Chinese medicine and Western medicine have their own characteristics in the treatment of this disease. Western medicine for the treatment of acute pharyngitis are mainly antiviral, antibiotic and glucocorticoid drugs, whose disadvantages are toxicity, side effects, drug resistance and double infections. Traditional Chinese medicine doctors have rich experiences in the treatment of the disease, which is characterized by treatment determination based on syndrome differentiation, safe and reliable medication, significant curative effect, low drug resistance, and wide varieties of traditional Chinese medicine forms, convenient portability and taking, low price, and low toxic and side effects. It is an arduous and significant task to explore traditional Chinese medicine, and study and develop new-type effective drugs.

Management of Pyogenic Cerebral Ventriculitis by Neuroendoscopic Surgery.

BACKGROUND: Pyogenic cerebral ventriculitis is a debilitating form of intracranial infection with an unfavorable outcome as a result of lack of experience in surgical management. OBJECTIVE: To study retrospectively a group of pyogenic cerebral ventriculitis patients managed by neuroendoscopic surgery (NES). METHODS: The standard intraventricular protocols of NES to treat this disease included 1 or more of the following: 1) obliteration of debris, 2) evidence of microbial infection, 3) septomy, 4) incision of the septation, or 5) monitoring catheter insertion. Modified external ventricular drainage EVD (mEVD) was combined with NES when intraventricular debris and bacterial plaques could not be evacuated completely. Subsequent surgical treatment strategies depended on the clinical manifestation, cerebrospinal fluid analysis, and mEVD blockage tests approximately 3 weeks after the last NES. RESULTS: Forty-one patients, who were distributed in 7 hospitals and underwent NES, were included. Five patients received 1 NES, 18 received 2, 16 received 3, and 2 received 4. mEVD was performed in all patients, and mean mEVD duration in the hospital was 27.6 days. At discharge, 15 patients were cured, 15 were cured but ventriculoperitoneal shunt dependent, 9 were mEVD dependent, and 2 died (mean modified Rankin Scale score was 2.48). Two mEVD-dependent patients died, and no other outcomes changed during postoperative follow-up (mean modified Rankin Scale score, 2.67). CONCLUSIONS: The results suggest a relatively favorable outcome for management of pyogenic cerebral ventriculitis by NES. The techniques and strategies are practical and should be applied more extensively.

[Microbial anaerobic dechlorination of polychlorinated biphenyls in paddy soil slurry].

We studied the dechlorination process of Aroclor1260, a high-chlorinated polychlorinated biphenyls (PCBs) mixture in an anaerobic paddy soil slurry, and further analyzed the related microbial community structures. The Aroclor1260 was reduced up to 55.5% in the natural paddy soil slurry in 128 days, and the reduction percentage dropped to 46.9% after incoculating the paddy soil slurry with a PCBs-dechlorination enrichment culture. The dechlorination mainly occurred in congeners of pentachlorobiphenyl, hexachlorobiphenyl, and specially, the heptachlorobiphenyl, with pentachlorobiphenyl accumulated as dechlorination intermediate. Hydrogen gas produced from fermentation of organic matters was maintained at a lower partial pressure due to its consumption during the dechlorination process, so that the methanogens was suppressed as well. The microbial community structure was significantly different between natural and inoculated paddy soils. Introducing the PCBs-dechlorination enrichment culture changed the local microbial community by the competition between the exogenetic dchlorinators and the indigenous bacteria, overall decreasing the dechlorination activity.

[Study on MSO/GO-based determination method for trace amount of aqueous Hg2+].

OBJECTIVE: To establish a highly sensitive fluorometric nanobiosensor for determination of aqueous mercury ions (Hg(2+)) using optimized mercury-specific oligonucleotide (MSO) probes and graphene oxide (GO). METHODS: The nanobiosensor was assembled by attaching the self-designed MSO(1) (5' end labeled with fluorophore carboxyfluorescein (FAM), denoted as FAM-MSO(1)) and MSO(2) to the surface of GO through strong non-covalent bonding forces. Upon the addition of Hg(2+), the formation of the T-Hg(2+)-T configuration desorbed the FAM-MSO(1) and MSO(2) from the surface of GO, resulting in a restoration of the fluorescence of FAM-MSO(1). Using the specific mispairing of T-Hg(2+)-T and the changes in fluorescent signals in solutions, quantitative analysis of Hg(2+) could be performed. RESULTS: The average thickness of the prepared GO sheets was only 1.4 nm. For the Hg(2+) nanobiosensor, the optimum concentrations of FAM-MSO(1) and MSO(2) were both 1 µmol/L, the optimum volume of 0.5 g/L GO was 5 µL, and the limit of detection was 10 pmol/L; it had low cross-reactivity with 10 other kinds of non-specific metal ions; the fluorescence recovery efficiency was up to 65% in the re-determination of Hg(2+) after addition of Na(2)S(2)O(3). CONCLUSION: The MSO/GO-based nanobiosensor is convenient to operate, highly sensitive, highly specific, highly accurate, and reusable. It can be applied to determine trace amount of Hg(2+) in aqueous solutions.

[Detection of mercury (II) ions (Hg(2+)) in water by a nanobiosensor].

OBJECTIVE: To develop a nanobiosensor for rapid colorimetric detecting Mercury (II) Ions (Hg(2+)) in water by mercury-specific oligonucleotides (MSOs) probe and gold nanoparticles. METHODS: The nanobiosensor was assembled by adsorbing the optimized MSOs on the surface of gold nanoparticles. A direct colorimetric probe of Hg(2+) which relied on the T-T mismatches in DNA duplexes was used to selectively and strongly capture Hg(2+). Hg(2+) induces the aggregation of gold nanoparticles with appropriate amount of salts, resulting the color change (red to blue). RESULTS: The diameter and concentration of the gold nanoparticle preparation were 15 nm and 2.97 nmol/L, respectively. Truncated MSOs (9 bp) showed the similar Hg(2+)-binding activity. The optimum concentration of the NaNO3 solution was 0.5 mol/L. The nanobiosensor could detect Hg(2+)in a range of 10 ∼ 1000 µmol/L within few minutes and the specificity was 100%. CONCLUSION: A new nanobiosensor is developed successfully for rapid colorimetric detecting Hg(2+) in water, avoiding either MSOs labeling or gold nanoparticles modification. This technique is simple, convenient and rapid detecting method with high sensitivity and specificity.

[Preparation and characterization of monoclonal antibodies against RalB].

OBJECTIVE: In order to explore the expression of RalB (ras related; GTP binding protein B) in mammal eucaryotic cell, we prepared and characterized monoclonal antibodies against RalB. METHODS: Hybridomas were generated by the fusion with Sp2/0 myelomas and spleen cells, which were from mice immunized with RalB recombinant proteins. The monoclonal antibodies against RalB were then used to identify the expression of RalB in mammal eucaryotic cell, including normal hepatic cell and hepatoma carcinoma cells, by Western blot and Immunohistochemistry. RESULTS: Two hybridoma cell lines, F001, F002, had been produced, each of which stably secrets antibodies against RalB. Subclass of IgG are both belonged to IgG1. Immunohistochemistry demonstrated that RalB was presented in plasma membrane of hepatoma tissue. Western-blot showed that RalB was expressed in all concerned cell. CONCLUSION: The monoclonal antibodies against RalB protein have been successfully prepared, which should provide useful reagent for further investigation into the biological function of RalB.