Emerging evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The microbiota-gut-brain axis plays a crucial role in the development and progression of PD, and numerous studies have demonstrated the potential therapeutic benefits of modulations in the intestinal microbiota. This review provides insights into the characterization of the gut microbiota in patients with PD and highlights associations with clinical symptoms and underlying mechanisms. The discussion underscores the increased influence of the gut microbiota in the pathogenesis of PD. While the relationship is not fully elucidated, existing research demonstrates a strong correlation between changes in the composition of gut microbiota and disease development, and further investigation is warranted to explain the specific underlying mechanisms.
Humans ; Parkinson Disease/microbiology* ; Gastrointestinal Microbiome/physiology* ; Dysbiosis/microbiology*

ObjectiveTo understand the distribution of enrofloxacin (ENR) residues in freshwater fish, to evaluate the dietary exposure risk to ENR for consumers through the consumption of different freshwater fish in Shanghai, and to provide a reference for controlling antibiotic residues in freshwater fish. MethodsGrass carp, Wuchang bream, pond loach, and Asian swamp eels were purchased from the markets in Shanghai. After being fed with ENR, the fish were divided into 42 batches according to their species and weight, and thereafter ENR residues in the muscles and skin of the fish were measured. In addition, a total of 44 batches of Wuchang bream, pond loach, Asian swamp eels were purchased from the markets, and the ENR residues in the muscles with or without the fish skin were measured, and the exposure risk was evaluated. ResultsThe average residues of ENR in skin of the freshwater fish after being fed with drugs in the 42 groups were higher than those in muscles (M=659.38 μg·kg^-1, M=460.83 μg·kg^-1; z=-2.212, P=0.027). The over-standard rates of ENR residues in the muscles with or without skin 44 batches of freshwater fish of sold in Shanghai were 36.36% and 29.55%, respectively. The median exposure, P₉₅ exposure, and maximum exposure to ENR through the consumption of the muscles with the skin for adults and children in Shanghai were higher than those through the consumption of muscles without the skin. For children, the margin of safety (MOS) for the max exposure to ENR by consuming the muscles with the skin was more than 1, while the MOS was less than 1 in all other cases for both children and adults. ConclusionThe ENR residues in the skin of freshwater fish are generally higher than those in the muscles. The risk of ENR residues in freshwater fish sold in Shanghai is within a controllable range. However, there might be a certain risk of acute exposure to ENR for children by consuming muscles with the skin of freshwater fish.

To study the prevalence of depression, anxiety, and insomnia among social workers during the prolonged battle against the COVID-19 pandemic and explore the associated risk factors.

BACKGROUND: Women comprise more than half of people living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) worldwide and incomplete immune recovery and metabolic abnormalities affect them deeply. Studies of HIV antiretroviral therapy (ART) have a low female representation in China. We aimed to investigate immune reconstitution and metabolic changes of female HIV-positive cohort in China longitudinally. METHODS: HIV-positive women who initiated ART from January 2005 to June 2021 and were followed up regularly at least once a year were included in this study. Immunological indicators (cluster of differentiation 4 [CD4] counts and CD8 counts), viral load (VL), and metabolic indicators were collected at follow-up. All data were collected from the China Disease Prevention and Control Information System (CDPCIS). VL was tested half a year, 1 year after receiving ART, and every other year subsequently according to local policy. CD4/CD8 ratio normalization was considered as the primary outcome and defined as a value ≥1. Incidence rate and probability of CD4/CD8 ratio normalization were estimated through per 100 person-years follow-up (PYFU) and Kaplan-Meier curve, respectively. Multivariate Cox regression was used to identify independent risk factors associated with CD4/CD8 ratio normalization. We further studied the rate of dyslipidemia, hyperuricemia, diabetes, liver injury, and renal injury after ART initiation with the chi-squared tests or Fisher's exact probability tests, and a generalized estimating equation model was used to analyze factors of dyslipidemia and hyperuricemia. RESULTS: A total of 494 female patients with HIV/AIDS started ART within 16 years from January 2005 to June 2021, out of which 301 women were enrolled with a median duration of ART for 4.1 years (interquartile range, 2.3-7.0 years). The overall incidence rate of CD4/CD8 ratio normalization was 8.9 (95% confidence interval [CI], 7.4-10.6) per 100 PYFU, and probabilities of CD4/CD8 normalization after initiating ART at 1 year, 2 years, 5 years, and 10 years follow-up were 11.7%, 23.2%, 44.0%, and 59.0%, respectively. Independent risk factors associated with CD4/CD8 normalization were baseline CD4 cell counts <200 cells/μL, CD8 counts >1000 cells/μL, and more than 6 months from the start of combined ART (cART) to first virological suppression. Longitudinally, the rate of hypercholesterolemia (total cholesterol [TC]) and high triglyceride (TG) showed an increasing trend, while the rate of low high-density lipoprotein cholesterol (HDL) showed a decreasing trend. The rate of hyperuricemia presented a downtrend at follow-up. Although liver and renal injury and diabetes persisted during ART, the rate was not statistically significant. Older age and protease inhibitors were independent risk factors for increase of TC and TG, and ART duration was an independent factor for elevation of TC and recovery of HDL-C. CONCLUSIONS This study showed that women were more likely to normalize CD4/CD8 ratio in comparison with findings reported in the literature even though immune reconstruction was incomplete.
Humans ; Female ; CD4-CD8 Ratio ; HIV ; Immune Reconstitution ; Hyperuricemia/drug therapy* ; HIV Infections/drug therapy* ; Acquired Immunodeficiency Syndrome/drug therapy* ; Anti-Retroviral Agents/therapeutic use* ; Cholesterol ; Viral Load ; CD4 Lymphocyte Count ; Anti-HIV Agents/therapeutic use*

Objective:To explore the clinical application of time of flight-magnetic resonance angiography (TOF-MRA), silent magnetic resonance angiography (SilenZ-MRA) and high-resolution vessel wall imaging (HR-VWI) in non-invasive evaluation of intracranial aneurysm after embolization.Methods:From February 2021 to February 2022, 39 patients, including 8 males and 31 females, who were 29-86 (54.50±11.80) years old and had received intracranial aneurysm embolization were collected in the Second Affiliated Hospital of Nanchang University. Kruskal-Wallis test was used to compare the image quality score and the evaluation results of lumen stenosis rate in the stent segments by TOF-MRA, SilenZ-MRA and HR-VWI. The diagnostic value of TOF-MRA, SilenZ-MRA and HR-VWI was analyzed by receiver operating characteristic (ROC) curve with DSA as the reference standard.Results:The image quality scores of TOF-MRA, SilenZ-MRA and HR-VWI were 2(1, 3), 4(3, 4) and 4(4, 4), respectively, with statistically significant difference ( H=80.78, P<0.05). The pairwise comparison results were as follows: TOF-MRA vs SilenZ-MRA, P<0.017; TOF-MRA vs HR-VWI, P<0.017; SilenZ-MRA vs HR-VWI, P>0.017. The lumen stenosis rates of stent segments measured by TOF-MRA, SilenZ-MRA, HR-VWI and DSA were 45.00% (29.60%, 61.05%), 17.60% (10.80%, 26.80%), 13.35% (8.90%, 15.95%) and 7.95% (4.80%, 11.25%), respectively, with statistically significant difference ( H=67.96, P<0.05). The results of comparison between TOF-MRA, SilenZ-MRA, HR-VWI and DSA were respectively as follows: TOF-MRA vs DSA, P<0.017; SilenZ-MRA vs DSA, P<0.017; HR-VWI vs DSA, P>0.017. DSA review showed that 12 (27.91%,12/43) aneurysms were not completely embolized, and 31 (72.09%, 31/43) aneurysms were completely embolized. The area under the curve of TOF-MRA, SilenZ-MRA and HR-VWI for evaluating the postoperative complete embolization of aneurysm was 0.75, 1.00 and 0.94, respectively, with statistically significant differences between TOF-MRA and HR-VWI ( Z=2.53, P<0.05) as well as between TOF-MRA and SilenZ-MRA ( Z=3.32, P<0.05). Conclusions:HR-VWI can clearly display the stent-segment lumen of the parent artery, and evaluate the stent-segment arterial wall and whether the stent-segment lumen is unobstructed or not. SilenZ-MRA is significantly superior to TOF-MRA in the evaluation of postoperative embolization status of aneurysms, and slightly superior to HR-VWI in tumor neck display. Combined application of HR-VWI and SilenZ-MRA has certain clinical significance for non-invasive evaluation of intracranial aneurysm after embolization.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective To investigate the effect of carrimycin on the biological function of pancreatic cancer cells. Methods Pancreatic cancer cell lines MIA PaCa-2, BxPC-3, Panc-1, and PATU 8988 were treated with carrimycin at concentrations of 0 (control group), 2, 4, 8, and 16 μmol/L for 24, 48, and 72 hours. MTT assay was used to measure cell viability; EdU cell proliferation assay was used to observe the effect of carrimycin on DNA replication of pancreatic cancer cells; colony formation assay was used to observe the effect of carrimycin on the proliferation of pancreatic cancer cells; flow cytometry was used to analyze the effect of carrimycin on the cell cycle of pancreatic cancer cells; wound healing assay was used to analyze the effect of carrimycin on the migration of pancreatic cancer cells; Western blot was used to measure the expression levels of the markers such as epithelial-mesenchymal transition (EMT) and cell cycle-dependent protein kinase inhibitor 1A (P21); immunofluorescence assay were used to measure the expression levels of EMT-related markers. An analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the control group, carrimycin significantly inhibited the proliferative activity of MIA PaCa-2, BxPC-3, Panc-1, and PATU 8988 cells in a concentration- and time-dependent manner (all P < 0.01); carrimycin at concentrations of 4, 8, and 16 μmol/L significantly reduced DNA replication in MIA PaCa-2 cells ( t =2.378, 4.984, and 18.970, all P < 0.05) and BxPC-3 cells ( t =4.879, 6.089, and 9.521, all P < 0.01); after treatment with carrimycin at concentrations of 4, 8, and 16 μmol/L, colony formation ability significantly decreased with the increase in drug concentration in MIA PaCa-2 cells ( t =5.889, 11.240, and 15.840, all P < 0.001) and BxPC-3 cells ( t =6.717, 15.800, and 18.850, all P < 0.001). After treatment with carrimycin at concentrations of 4, 8, and 16 μmol/L, there was a significant increase in the proportion of cells in G1 phase in MIA PaCa-2 cells ( t =9.071, 12.280, and 19.360, all P < 0.0001) and BxPC-3 cells ( t =3.061, 4.962, and 8.868, all P < 0.05), and there was a significant reduction in the proportion of cells in S phase in MIA PaCa-2 cells ( t =2.316, 4.165, and 5.562, all P < 0.05) and BxPC-3 cells ( t =2.424, 3.264, and 5.744, all P < 0.05). Western blot further demonstrated that compared with the control group, the expression level of the cell cycle-related protein P21 gradually increased with the increase in the concentration of carrimycin in MIA PaCa-2 cells ( t =5.437, 6.453, and 8.799, all P < 0.001) and BxPC-3 cells ( t =25.130, 44.750, and 52.960, all P < 0.000 1). Wound healing assay showed that after treatment for 12, 24, and 48 hours, carrimycin at concentrations of 0, 4, 8, and 16 μmol/L significantly reduced the lateral migration of MIA PaCa-2 cells (all P < 0.05) and BxPC-3 cells (all P < 0.05). Western blot showed that compared with the control group, carrimycin treatment at concentrations of 4, 8, and 16 μmol/L significantly upregulated the expression of the epithelial marker E-cadherin in MIA PaCa-2 cells ( t =2.388, 4.899, and 5.819, all P < 0.05) and BxPC-3 cells ( t =2.533, 5.836, and 6.774, all P < 0.05) and significantly downregulated the expression of the interstitial marker Snail in MIA PaCa-2 cells ( t =12.440, 14.830, and 16.800, all P < 0.000 1) and BxPC-3 cells ( t=5.039, 5.893, and 7.725, all P < 0.01), and it also significantly downregulated the expression of the interstitial marker Vimentin in MIA PaCa-2 cells ( t =3.105, 7.752, and 11.200, all P < 0.05) and BxPC-3 cells ( t =2.555, 4.883, and 9.153, all P < 0.05). Conclusion Carrimycin can effectively inhibit the proliferation, migration, and EMT process of pancreatic cancer cells, thereby exerting an antitumor biological activity.

Objective:To investigate the clinical situation of 201 emergency adult sudden death patients, and analyze the influence of white blood cell count and arterial blood lactate level on prognosis.Methods:The clinical data of 201 patients diagnosed with sudden death in the emergency department of Medical College of Cangzhou people's Hospital from January 2017 to January 2021 were retrospectively analyzed. The gender, age, disease composition and etiology of the patients were statistically analyzed. The independent sample t-test was used to compare the measurement data with normal distribution, the χ 2 test or Fisher exact probability method was used to compare the counting data between groups, and the logistic regression model was used to screen the risk factors of emergency death, and the impact of white blood cell count and arterial blood lactate level on the prognosis was analyzed. Results:After active rescue, 11.44% (23/201) of the patients were successfully rescued, and 88.56% (178/201) of the patients were ineffective; ≥46-≤65 years old was the age group with high incidence of sudden death (55.22%(111/201)). The proportion of male (43.28% (87/201), 23.38% (42/201)) in the age group of ≥46-≤65 years old and the age group over 65 years old were higher than that of female (11.94% (24/201), 14.43% (29/201)), with a statistically significant difference (χ 2=4.801, 9.209; P=0.028, 0.002). In the past history of sudden death patients, the proportion of cardiovascular disease (53.23% (107/201)) was the highest; the proportion of patients may have inducements before sudden death was 74.13% (149/201), the proportion of patients have premonitory symptoms before sudden death was 67.66% (136/201), and sudden cardiac death was the first cause. Logistic regression analysis showed that white blood cell count ( OR=4.442,95% CI: 1.898-10.395), arterial blood lactic acid concentration ( OR=4.272,95% CI: 2.024-9.016), and albumin concentration ( OR=2.657,95% CI: 1.302-5.422) were independent risk factors affecting emergency sudden death patients ( P values were 0.001, <0.001, 0.007, respectively). Conclusions:There are some differences in gender, age and past history of adult sudden death patients. Most of them have premonitory symptoms and inducements. Sudden cardiac death is the primary cause. The increases of white blood cell count and lactic acid level, the decrease of albumin level are the risk factors of sudden death.

ObjectiveTo reveal the effect of Wenxin prescription on mitochondrial energy metabolism and silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α）/recombinant estrogen-related receptor α （ERRα） signaling pathway in rats with myocardial ischemia-reperfusion injury. MethodTotally 90 male Wistar rats of SPF grade were randomly assigned into a sham operation group， a model group， and low-， medium-， and high-dose Wenxin prescription groups， with 18 rats in each group. The rats in low-， medium-， and high-dose Wenxin prescription groups were administrated with 0.99， 1.98， and 3.96 g·kg^-1 granules by gavage， respectively， and those in the sham operation group and model group with the same amount of normal saline. Twenty-one days after pre-administration， the rat model of myocardial ischemia-reperfusion injury was established by ligation of the left anterior descending coronary artery for 30 min and reperfusion for 2 h， and the rats in the sham operation group were only threaded without ligation. Myocardial infarction area was observed through 2，3，5-triphenyl-2h-tetrazolium chloride （TTC） staining， and the myocardial histopathology through hematoxylin-eosin （HE） staining. The levels of creatine kinase-MB （CK-MB） and lactate dehydrogenase （LDH） in serum， cytochrome C oxidase （CCO） and succinate dehydrogenase （SDH） in mitochondrion， and ATP in myocardial tissue were detected according to kit instructions. The mRNA and protein levels of SIRT1， PGC-1α， ERRα， and mitochondrial transcription factor A （TFAM） in myocardial tissue were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham operation group， the model group showed broken and disordered myocardial fibers， cytoplasmic edema， and pyknosis and deviation of nuclei. Moreover， the modeling increased the levels of CK-MB and LDH （P<0.05， P<0.01）， lowered the levels of ATP， CCO， and SDH （P<0.05， P<0.01）， and down-regulated the mRNA and protein levels of SIRT1， PGC-1α， ERRα， and TFAM in myocardial tissue （P<0.05， P<0.01）. Compared with the model group， Wenxin prescription reduced the myocardial infarction area （especially in the high-dose group， P<0.01）， restored the pathological changes， lowered the levels of CK-MB and LDH （P<0.05， P<0.01）， increased the levels of ATP， CCO， and SDH （especially in the high-dose group， P<0.01）， and up-regulated the mRNA and protein levels of SIRT1， PGC-1α， ERRα， and TFAM in myocardial tissue （P<0.05， P<0.01）. ConclusionWenxin prescription can protect rats from myocardial ischemia-reperfusion injury by regulating myocardial mitochondrial energy metabolism via the SIRT1/PGC-1α/ERRα signaling pathway.

Objective:To investigate the effects of different durations of antiretroviral therapy (ART) on metabolism in HIV/AIDS patients.Methods:a single center cross-sectional study, 424 HIV/AIDS were divided into four groups according to the different duration of treatment: group Ⅰ (0.5-2 years), group Ⅱ (2-4 years including 2 years), the group Ⅲ (4-6 years including 4 years), group Ⅳ (≥6 years), the differences of abnormal blood lipid, renal function, blood glucose and liver function in each group were compared.Results:incidence of hypercholesteremia: group Ⅰ 9/106 (8.5%), group Ⅱ 17/134 (12.7%), group Ⅲ 22/123 (17.9%), group Ⅳ 4/61 (6.6%), p=0.076; incidence of hypertriglyceridemia: groupⅠ 32/106 (30.2%), group Ⅱ 58/134 (43.3%), group Ⅲ 50/123 (40.7%), group Ⅳ 27/61 (44.3%), p=0.152; incidence of High LDL-C: group Ⅰ 8/106 (7.5%), group Ⅱ 17/134 (12.7%), group Ⅲ 15/123 (12.2%), group Ⅳ 3/61 (4.9%), p=0.249; Incidence of low HDL-C: groupⅠ 48/106 (45.3%), group Ⅱ 66/134 (49.3%), group Ⅲ 55/123 (44.7%), group Ⅳ 33/61 (54.1%), p=0.612; incidence of glomerular filtration rate < 90 ml/min / 1.73 m2: groupⅠ4/106 (3.8%), group Ⅱ 6/134 (4.5%), group Ⅲ 6/123 (4.9%), group Ⅳ 2/61 (3.3%), P=0.953; eGFR was negatively correlated with treatment duration (r=-0.165, P <0.001). Incidence of hypophosphatemia: group Ⅰ 7/106 (6.6%), group Ⅱ 7/134 (5.2%), group Ⅲ 12/123 (9.8%), group Ⅳ 6/61 (9.8%), P=0.478; incidence of hyperuricemia: groupⅠ26/106 (24.5%), group Ⅱ 35/134 (26.1%), group Ⅲ 28/123 (22.8%), group Ⅳ 10/61 (16.4%), P=0.508; incidence of diabetes: groupⅠ1/106 (0.9%), group Ⅱ 9/134 (6.7%), group Ⅲ 6/123 (4.9%), group Ⅳ 3/61 (4.9%), P=0.140; incidence of GGT > 60 U/L: group Ⅰ(21.7%), 23 group Ⅱof 34 (25.4%), 25 group Ⅲ (20.3%), group Ⅳ of 12 (19.7%), P=0.736; incidence of ALT > 50 U/L: groupⅠ(21.7%), 23 group Ⅱ of 33 (24.6%), group Ⅲ of 24 (19.5%), group Ⅳ of 12 (19.7%), p=0.761Conclusion:The types of dyslipidemia in HIV/AIDS patients treated for more than half a year are mainly low HDL-C and hypertriglyceridemia, and the incidence of dyslipidemia does not increase with the prolonging of treatment. It showed a decreasing trend of eGFR with the prolongation of treatment and the occurrence of hypophosphatemia and hyperuricemia should be concerned. The damage of ART drugs to liver function persisted during treatment.