Physical fitness decline and career paths: a longitudinal study of medical undergraduates.

INTRODUCTION: Exercise enhances one's health and competitiveness. A strong physical fitness status can pave the way for a promising future. This study presents the time-based trends in physical fitness indicators-including height, weight, BMI, lung capacity, dash, long-distance running, and standing long jump-among medical undergraduates during their university years. Additionally, we analyzed the impact of students' physical fitness on their career paths. METHOD: We conducted a retrospective database study by collecting physical fitness test data and career paths information for 634 medical students from a university in southwestern China. These students graduated in 2022. The career paths included pursuits in further studies, employment, and unemployment. To detect differences in these aspects, we used the t-test and Chi-square test. RESULTS: Our study indicates a significant declining trend in the physical fitness of medical students during their university years. The changes observed between the first and fourth tests are as follows: Weight (kg): 58.52 ± 10.48 to 60.73 ± 12.07, P < 0.00 BMI (kg/m^2): 20.79 ± 2.74 to 21.24 ± 3.06, P < 0.00 50-m dash (s): 8.91 ± 0.99 to 9.25 ± 1.11, P < 0.00 Standing long jump (cm): 187.74 ± 30.98 to 182.59 ± 32.25, P < 0.00 800-m run for females (min): 3.84 ± 0.47 to 4.48 ± 0.85, P < 0.00 1000-m run for males (min): 3.98 ± 0.63 to 4.62 ± 0.87, P < 0.00 Sit-ups for females (count): 30.39 ± 7.5 to 29.03 ± 8.82, P < 0.00 Upon analyzing the correlation between changes in physical fitness and career paths, students with stable or decreased BMI had better post-graduation outcomes compared to students with increased BMI. CONCLUSIONS: Medical students show a declining trend in physical fitness during their undergraduate years. A good physical health status is beneficial for achieving better career paths. Medical students should place greater emphasis on physical exercise during their time in school.

Enhanced oral and pulmonary delivery of biomacromolecules via amplified transporter targeting.

Ligand-modified nanocarriers can promote oral or inhalative administration of macromolecular drugs across the intestinal or pulmonary mucosa. However, enhancing the unidirectional transport of the nanocarriers through "apical uptake→intracellular transport→basolateral exocytosis" route remains a hot topic and challenge in current research. Forskolin is a naturally occurring diterpenoid compound extracted from the roots of C. forskohlii. In our studies, we found that forskolin could increase the transcellular transport of butyrate-modified nanoparticles by 1.67-fold and 1.20-fold in Caco-2 intestinal epithelial cell models and Calu-3 lung epithelial cell models, respectively. Further mechanistic studies revealed that forskolin, on the one hand, promoted the cellular uptake of butyrate-modified nanoparticles by upregulating the expression of monocarboxylic acid transporter-1 (MCT-1) on the apical membrane. On the other hand, forskolin facilitated the binding of MCT-1 to caveolae, thereby mediating butyrate-modified nanoparticles hijacking caveolae to promote the basolateral exocytosis of butyrate-modified nanoparticles. Studies in normal mice model showed that forskolin could promote the transmucosal absorption of butyrate-modified nanoparticles by >2-fold, regardless of oral or inhalative administration. Using semaglutide as the model drug, both oral and inhalation delivery approaches demonstrated significant hypoglycemic effects in type 2 diabetes mice model, in which inhalative administration was more effective than oral administration. This study optimized the strategies aimed at enhancing the transmucosal absorption of ligand-modified nanocarriers in the intestinal or pulmonary mucosa.

Manganese induces podocyte injury through regulating MTDH/ALKBH5/NLRP10 axis: Combined analysis at epidemiology and molecular biology levels.

Manganese (Mn) is an essential micronutrient required for various biological processes but excess exposure to Mn can cause neurotoxicity. However, there are few reports regarding the toxicity effect of Mn on the kidney as well as the underlying molecule mechanism. Herein, in vivo experiments were adopted to assess the toxicity effects associated with Mn, and found that chronic Mn treatment induced the injury of glomerular podocytes but not renal tubule in rats. Genome-wide CRISPR/Cas9 knockout screen was then employed to explore the biotargets of the toxic effect of Mn on podocytes. Through functional analyses of the enriched candidate genes, NLRP10 was found to be significantly up-regulated and mediated Mn-induced podocyte apoptosis. Further mechanism investigation revealed that NLRP10 expression was regulated by demethylase AlkB homolog 5 (ALKBH5) in an m6A-dependent fashion upon Mn treatment. Moreover, Mn could directly bind to Metadherin (MTDH) and promoted its combination with ALKBH5 to promote NLRP10 expression and cell apoptosis. Finally, logistic regressions, restricted cubic spline regressions and uniform cubic B-spline were used to investigate the association between Mn exposure and the risk of chronic kidney disease (CKD). A U-shaped nonlinear relationship between CKD risk and plasma Mn level, and a positive linear relationship between CKD risk and urinary Mn levels was found in our case-control study. To sum up, our findings illustrated that m6A-dependent NLRP10 regulation is indispensable for podocyte apoptosis and nephrotoxicity induced by Mn, providing fresh insight into understanding the health risk of Mn and a novel target for preventing renal injury in Mn-intoxicated patients.

Chiral Bis-phosphate Macrocycles for Catalytic, Efficient, and Enantioselective Electrophilic Fluorination.

Incorporation of privileged catalytic scaffolds into a macrocyclic skeleton represents an attractive strategy to furnish supramolecular catalysis systems with enzyme-mimetic cavity and multi-site cooperation. Herein we reported the synthesis, structure, binding properties and catalytic application of a series of chiral bis-phosphate macrocycles toward the challenging asymmetric electrophilic fluorination. With a large, integrated chiral cavity and two cooperative phosphate sites, these macrocycles exhibited good inclusion toward 1,4-diazabicyclo[2.2.2]octane (DABCO) dicationic ammoniums through complementary ion-pair and C-H⋅⋅⋅O interactions, as confirmed by crystallographic and solution binding studies. In fluorocyclization of tryptamines with Selectfluor reagent which has a similar DABCO-based dicationic structure, only 2 mol% macrocycle catalyst afforded the desired pyrroloindoline products in moderate yields and up to 91 % ee. For comparison, the acyclic mono-phosphate analogue gave obviously lower reactivity and enantioselectivity (<20 % ee), suggesting a remarkable macrocyclic effect. The high catalytic efficiency and superior stereocontrol were ascribed to the tight ion-pair binding and cavity-directed noncovalent interaction cooperation.

Effect of the Water Content on the Adsorption of CO2 and CH4 in Calcite Slit Nanopores: Insights from GCMC, MD, and DFT.

It is significant to understand the adsorption mechanisms of shale gas (CH4) and CO2 in shale formations to enhance CH4 recovery rates and enable geological CO2 storage. This study provides a comprehensive investigation into the adsorption behaviors of CO2 and CH4 within dry and hydrous calcite nanopores, utilizing a combination of grand canonical Monte Carlo simulations, molecular dynamics simulations, and density functional theory calculations. In dry calcite slits, the calculated results for the adsorption capacity, density profile, and isosteric heat of CO2 and CH4 reveal that CO2 possesses a stronger adsorption affinity, making it preferentially adsorb on the pore surface compared to CH4. In hydrous calcite slits, calculating the adsorption capacity and density profile of CO2 and CH4, the results show that the gas adsorption sites become progressively occupied by H2O molecules, leading to a substantial decrease in the adsorption capacity of CO2 and CH4. Furthermore, by analysis of the adsorption energy and electronic structure, the reason for the reduction of gas adsorption capacity caused by H2O is further revealed. This work has a deep understanding of the adsorption mechanisms of shale gas and CO2 in calcite and can offer valuable theoretical insights for the development of a CO2-enhanced shale gas recovery technology.

Dance/movement therapy for improving balance ability and bone mineral density in long-term patients with schizophrenia: a randomized controlled trial.

Fractures are common accidents for long-term hospitalized patients with schizophrenia (SZ) in psychiatric hospitals, and once they occur, patients usually endure the pain of fractures for a long time. Accumulating evidence has supported the implementation of dance/movement therapy (DMT) as a promising intervention for patients with SZ. However, no research has been conducted to investigate its role in balance ability in SZ. This study was designed to investigate the efficacy of a 12-week DMT intervention in bone mineral density and balance ability in patients with SZ using a randomized, controlled trial design. A total of 58 veterans with SZ were randomly assigned to the DMT intervention group (n = 29) and the treatment-as-usual (TAU) group (n = 29). Bone mineral density (BMD) and balance ability were measured in both groups at two measurement points (at baseline and at the end of Week 12). We found that patients in the DMT intervention group had significant improvements in BMD and balance ability compared with the TAU group by using repeated measures analysis of variance. Treatment with DMT demonstrated a significant improvement in BMD from baseline to week 12 (0.03, 95% CI: 0.01-0.05). For the Berg total score and static and dynamic balance, the mean changes in the DMT group were 7.3 (95% CI: 5.6-9.0), 4.0 (95% CI: 0.9-7.1), and 3.7 (95% CI: 2.6-4.8), respectively. Regression analysis showed that baseline BMD was a significant predictor of improvement in BMD from baseline to week 12 in the DMT group (ß = 0.58, p < 0.001). Our results suggest for the first time that DMT intervention may be effective in beneficially regulating BMD and balance ability in SZ patients.

Metal mixture exposure and the risk for immunoglobulin A nephropathy: Evidence from weighted quantile sum regression.

Immunoglobulin A nephropathy (IgAN) is the most common type of glomerulonephritis in adults worldwide. Environmental metal exposure has been reported to be involved in the pathogenic mechanisms of kidney diseases, yet no further epidemiological study has been conducted to assess the effects of metal mixture exposure on IgAN risk. In this study, we conducted a matched case‒control design with three controls for each patient to investigate the association between metal mixture exposure and IgAN risk. A total of 160 IgAN patients and 480 healthy controls were matched for age and sex. Plasma levels of arsenic, lead, chromium, manganese, cobalt, copper, zinc, and vanadium were measured using inductively coupled plasma mass spectrometry. We used a conditional logistic regression model to assess the association between individual metals and IgAN risk, and a weighted quantile sum (WQS) regression model to analyze the effects of metal mixtures on IgAN risk. Restricted cubic splines were used to evaluate overall associations between plasma metal concentrations and estimated glomerular filtration rate (eGFR) levels. We observed that except for Cu, all the metals analyzed were nonlinearly associated with decreased eGFR, and higher concentrations of arsenic and lead were associated with elevated IgAN risk in both single-metal [3.29 (1.94, 5.57), 6.10 (3.39, 11.0), respectively] and multiple-metal [3.04 (1.66, 5.57), 4.70 (2.47, 8.97), respectively] models. Elevated manganese [1.76 (1.09, 2.83)] levels were associated with increased IgAN risk in the single-metal model. Copper was inversely related to IgAN risk in both single-metal [0.392 (0.238, 0.645)] and multiple-metal [0.357 (0.200, 0.638)] models. The WQS indices in both positive [2.04 (1.68, 2.47)] and negative [0.717 (0.603, 0.852)] directions were associated with IgAN risk. Lead, arsenic, and vanadium contributed significant weights (0.594, 0.195, and 0.191, respectively) in the positive direction; copper, cobalt, and chromium carried significant weights (0.538, 0.253, and 0.209, respectively). In conclusion, metal exposure was related to IgAN risk. Lead, arsenic, and copper were all significantly weighted factors of IgAN development, which may require further investigation.

Braided stent-assisted coil embolization versus laser engraved stent-assisted coil embolization in patients with unruptured complex intracranial aneurysms.

PURPOSES: Braided and laser-cut stents both are efficacious and safe for coiling intracranial aneurysms. The study aimed to compare outcomes following braided stent-assisted coil embolization versus laser engraved stent-assisted coil embolization in 266 patients who were diagnosed with unruptured intracranial aneurysms of different types and locations. METHODS: Patients with unruptured complex intracranial aneurysms underwent braided (BSE cohort, n = 125) or laser engraved (LSE cohort, n = 141) stent-assisted embolization. RESULTS: The deployment success rate was higher for patients of the LSE cohort than those of the BSE cohort (140 [99%] vs. 117 [94%], p = 0.0142). Seventy-one (fifty-seven percentages) and 73 (52%) were coil embolization procedure success rates of the BSE and the LSE cohorts. Periprocedural intracranial hemorrhage was higher in patients of the BSE cohort than those of the LSE cohort (8 [6%] vs. 1 [1%], p = 0.0142). Four (three percentages) patients from the LSE cohort and 3 (2%) patients from the BSE cohort had in-stent thrombosis during embolization. Permanent morbidities were higher in patients of the LSE cohort than those of the BSE cohort (8 [6%] vs. 1 [1%], p = 0.0389). Higher successful procedures (76% vs. 68%) and fewer postprocedural intracranial hemorrhage (0% vs. 5%) and mortality (0% vs. 5%) were reported for patients of the BSE cohort in posterior circulation aneurysmal location than those of the LSE cohort. Laser engraved stent has fewer problems with deployment and may have better periprocedural and follow-up outcomes after embolization. CONCLUSIONS: Braided stent-assisted embolization should be preferred when the aneurysm is present in the posterior circulation.

Modified Bamboo Charcoal as a Bifunctional Material for Methylene Blue Removal.

Biomass-derived raw bamboo charcoal (BC), NaOH-impregnated bamboo charcoal (BC-I), and magnetic bamboo charcoal (BC-IM) were fabricated and used as bio-adsorbents and Fenton-like catalysts for methylene blue removal. Compared to the raw biochar, a simple NaOH impregnation process significantly optimized the crystal structure, pore size distribution, and surface functional groups and increase the specific surface area from 1.4 to 63.0 m2/g. Further magnetization of the BC-I sample not only enhanced the surface area to 84.7 m2/g, but also improved the recycling convenience due to the superparamagnetism. The maximum adsorption capacity of BC, BC-I, and BC-IM for methylene blue at 328 K was 135.13, 220.26 and 497.51 mg/g, respectively. The pseudo-first-order rate constants k at 308 K for BC, BC-I, and BC-IM catalytic degradation in the presence of H2O2 were 0.198, 0.351, and 1.542 h-1, respectively. A synergistic mechanism between adsorption and radical processes was proposed.

Air pollution associated with incidence and progression trajectory of chronic lung diseases: a population-based cohort study.

BACKGROUND: No prior study has examined the effects of air pollution on the progression from healthy to chronic lung disease, subsequent chronic lung multimorbidity and further to death. METHODS: We used data from the UK Biobank of 265 506 adults free of chronic lung disease at recruitment. Chronic lung multimorbidity was defined as the coexistence of at least two chronic lung diseases, including asthma, chronic obstructive pulmonary disease and lung cancer. The concentrations of air pollutants were estimated using land-use regression models. Multistate models were applied to assess the effect of air pollution on the progression of chronic lung multimorbidity. RESULTS: During a median follow-up of 11.9 years, 13 863 participants developed at least one chronic lung disease, 1055 developed chronic lung multimorbidity and 12 772 died. We observed differential associations of air pollution with different trajectories of chronic lung multimorbidity. Fine particulate matter showed the strongest association with all five transitions, with HRs (95% CI) per 5 µg/m3 increase of 1.31 (1.22 to 1.42) and 1.27 (1.01 to 1.57) for transitions from healthy to incident chronic lung disease and from incident chronic lung disease to chronic lung multimorbidity, and 1.32 (1.21 to 1.45), 1.24 (1.01 to 1.53) and 1.91 (1.14 to 3.20) for mortality risk from healthy, incident chronic lung disease and chronic lung multimorbidity, respectively. CONCLUSION: Our study provides the first evidence that ambient air pollution could affect the progression from free of chronic lung disease to incident chronic lung disease, chronic lung multimorbidity and death.

Braided stent-assisted coil embolization versus laser engraved stent-assisted coil embolization in patients with unruptured complex intracranial aneurysms

Abstract Purposes: Braided and laser-cut stents both are efficacious and safe for coiling intracranial aneurysms. The study aimed to compare outcomes following braided stent-assisted coil embolization versus laser engraved stent-assisted coil embolization in 266 patients who were diagnosed with unruptured intracranial aneurysms of different types and locations. Methods: Patients with unruptured complex intracranial aneurysms underwent braided (BSE cohort, n = 125) or laser engraved (LSE cohort, n = 141) stent-assisted embolization. Results: The deployment success rate was higher for patients of the LSE cohort than those of the BSE cohort (140 [99%] vs. 117 [94%], p = 0.0142). Seventy-one (fifty-seven percentages) and 73 (52%) were coil embolization procedure success rates of the BSE and the LSE cohorts. Periprocedural intracranial hemorrhage was higher in patients of the BSE cohort than those of the LSE cohort (8 [6%] vs. 1 [1%], p = 0.0142). Four (three percentages) patients from the LSE cohort and 3 (2%) patients from the BSE cohort had in-stent thrombosis during embolization. Permanent morbidities were higher in patients of the LSE cohort than those of the BSE cohort (8 [6%] vs. 1 [1%], p = 0.0389). Higher successful procedures (76% vs. 68%) and fewer postprocedural intracranial hemorrhage (0% vs. 5%) and mortality (0% vs. 5%) were reported for patients of the BSE cohort in posterior circulation aneurysmal location than those of the LSE cohort. Laser engraved stent has fewer problems with deployment and may have better periprocedural and follow-up outcomes after embolization. Conclusions: Braided stent-assisted embolization should be preferred when the aneurysm is present in the posterior circulation.

Household cooking oil type and risk of oral micronucleus frequency in Chinese nonsmokers.

Household animal fat has been linked to increased incidence of cancers compared with vegetable fat. However, few epidemiological studies have associated these two cooking oil types with precancerous genotoxic effects, such as occurrence of micronuclei (MN). This study aimed to explore the association between oral MN frequency and household cooking oil type and whether the association can be attributed to polycyclic aromatic hydrocarbons (PAHs). We collected information about individual cooking oil use, measured genotoxic effects by MN tests and urinary PAHs metabolites (OHPAHs) in 245 nonsmokers. The associations between household cooking oil type and MN frequency and OHPAHs were analyzed using generalized linear models (GLMs) and logistic regression models, evaluating odds ratios and coefficient (95% confidence intervals) (ORs, 95% Cls; ß, 95% Cls). The odds of animal fat consumers, rather than vegetable fat consumers, was positively associated with higher MN frequency (OR = 1.94, P < 0.05). The associations were discovered in participants only using kitchen ventilation (OR = 2.04, P < 0.05). Animal fat consumers had higher total OHPAHs than vegetable fat consumers (1.58 ± 0.22 mg/mol, Cr vs 1.20 ± 0.12 mg/mol, Cr; P = 0.028). Significant correlations were observed between total OHPAHs quartiles and increased MN frequency (ß = 0.38, P-trend = 0.026). After stratifying by household cooking oil type, sensitivity analyses showed that the positive association between total OHPAHs quartiles and increased MN frequency was only observed in animal fat consumers (ß = 0.61, P-trend = 0.030). In conclusion, usage of household animal fat was associated with an increased odds of oral MN frequency in Chinese nonsmokers and the odds correlated with increased PAHs exposure. This finding supplemented evidence associating cooking oil type with genotoxic effects and explained its association with PAHs exposure.

High-Temperature Soup Foods in Plastic Packaging Are Associated with Phthalate Body Burden and Expression of Inflammatory mRNAs: A Dietary Intervention Study.

Plastic packaging material is widely used to package high-temperature soup food in China, but this combination might lead to increased exposure to phthalates. The health effects and potential biological mechanisms have not been well studied. This study aimed to examine urinary phthalate metabolites and the expression of inflammatory cytokines in the blood before, during, and after a "plastic-packaged high-temperature soup food" dietary intervention in healthy adults. The results showed that compared with those in the preintervention period, urinary creatinine-adjusted levels of monomethyl phthalate (MMP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MIBP), and total phthalate metabolites in the intervention period were significantly higher, with increases of 71.6, 41.8, 38.8, and 29.8% for MMP, MBP, MIBP, and the total phthalate metabolites, respectively. After intervention, the mean levels of IL-1ß, IL-4, and TNF-α mRNA increased by 19.0, 21.5, and 25.0%, respectively, while IL-6 and IFN-γ mRNA decreased by 24.2 and 32.9%, respectively, when compared with the preintervention period. We also observed that several phthalates were associated with the mRNA or protein expression of IL-8, TNF-α, and IL-10. Therefore, consumption of plastic-packaged high-temperature soup food was linked to increased phthalate exposure and might result in significant changes in mRNA expression of several inflammatory cytokines.

[Metagenomic Analysis of Resistance Genes in Membrane Cleaning Sludge].

Wastewater treatment plants (WWTPs) are considered important reservoirs of antibiotic resistance genes (ARGs) and function as the main sources of ARGs in the environment. Membrane bioreactors (MBRs) have been recognized as effective tools for removing ARGs in WWTPs.There are a large number of pathogens and resistance genes in colloids, particulate matter, suspended matter, and microbial metabolites in intercepted wastewater by MBR. However, the distribution characteristics of resistance genes in membrane cleaning sludge remains unclear. In this study, resistance genes of membrane cleaning sludge were analyzed using a metagenomic technique. The results showed that there were 39 phyla in the membrane cleaning sludge. Proteobacteria, Nitrospirae, and Actinobacteria were the dominant phyla. The dominant genera were Nitrospira, Pseudomonas, and Bradyrhizobium. The pathogens accounted for 10.54% of all bacteria in the sample, among which Pseudomonas had the highest abundance, accounting for 3.94%. A total of 17 types of antibiotic resistance genes and 16 types of metal resistance genes (MRGs) (15 types of single metal resistance genes and 1 types of multi-heavy metal resistance gene) were identified. Multidrug resistance genes had the highest abundance, accounting for 49.08%. Multi-heavy metal resistance genes were the most abundant, accounting for 34.58%. The copper resistance genes were the most abundant of the single metal resistance genes, accounting for 19.99%. The most important functional pathway of microbial community in the membrane cleaning sludge was metabolic related, and many genes identified were related to human diseases. The numbers of genes related to bacterial resistance and bacterial infectious diseases were the largest, accounting for 34.50% and 16.62%, respectively. These results indicate that there were abundant ARGs, MRGs, and pathogens in the membrane cleaning sludge, which has potential environmental health risks. It is necessary to strengthen the control of ARGs, MRGs, and pathogens in membrane cleaning sludge to provide guidance for selecting appropriate technologies for effectively removing ARGs, MRGs, and pathogens.

Rapamycin inhibits LOC102553434-mediated pyroptosis to improve lung injury induced by limb ischemia-reperfusion.

Limb ischemia reperfusion (I/R) triggers local or systemic injury, and whether the process is mediated by pyroptosis remains unclear, we aimed to explore whether pyroptosis was involved in the process of rapamycin alleviating lung injury induced by I/R and investigate the molecular mechanisms. The histopathology of lung injury induced by I/R was confirmed by hematoxylin-eosin (HE) staining, and malondialdehyde (MDA), superoxide dismutase (SOD), and the expression of pyroptosis related molecules were detected. RNA sequencing was used to mine key long non-coding RNAs (lncRNAs). The model of lipopolysaccharide (LPS)-induced L2 cell damage was also used to explore the effect and mechanism of rapamycin on lncRNA. Rapamycin treatment alleviated I/R-induced lung histopathologically injury and increased the concentration of MDA while decreased activity of SOD and expression of NLRP3, Caspase-1, interleukin-1ß (IL-1ß), and IL-18 in rat. A total of 63 differentially expressed lncRNAs (DElncRNAs) were identified from IR + Rap group compared with IR group, and these DElncRNAs were mainly involved in cell adhesion molecules (CAMs) and endocytosis pathway. The lncRNA LOC102553434 and its target gene MMP9 were most significantly up-regulated in I/R-injured rat. In vitro experiments showed that LPS induction caused a significant increase in LOC102553434, MMP9, IL-1ß, and IL-18 in L2 cells, but rapamycin treatment significantly reversed the effects. After interfering with the expression of LOC102553434 in the LPS-injured cells pretreated with rapamycin, cell proliferation significantly increased, and the expression of MMP, NLRP3 and caspase-1 were significantly decreased. Rapamycin protects the lung from limb I/R injury by regulating LOC102553434 expression and inhibiting pyroptosis pathway. LOC102553434 plays a role in promoting pyroptosis and thus provides a target for clinical treatment of I/R-induced lung injury. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02708-9.

Therapeutic Response Is Associated With Antipsychotic-Induced Weight Gain in Drug-Naive First-Episode Patients With Schizophrenia: An 8-Week Prospective Study.

BACKGROUND: Some previous studies have shown that weight gain is associated with greater improvement in psychopathology during antipsychotic treatment in patients with chronic schizophrenia. However, the results are mixed due to many confounding factors. The current study aimed to investigate whether weight gain was associated with antipsychotic response in patients with antipsychotic-naive and first-episode (ANFE) DSM-IV--diagnosed schizophrenia. METHODS: 526 ANFE patients and 313 healthy controls were enrolled in this study, which was conducted from January 2012 to December 2018. Treatment outcome was measured by the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up. Weight was measured at baseline and at the end of 8 weeks. RESULTS: After treatment, PANSS scores were significantly reduced as follows: positive symptoms (-10.40; 95% CI, -9.31 to -10.60), negative symptoms (-5.01; 95% CI, -4.43 to -5.54), general psychopathology (-13.01; 95% CI, -12.01 to -14.01), and PANSS total score (-28.53; 95% CI, -26.73 to -30.33). In addition, the average weight of ANFE patients increased by 2.89 kg (95% CI, 2.55 to 3.22), although it was still lower than the average weight of healthy controls. The proportion of patients with weight gain ≥ 7% after treatment was 38.2%. Weight gain was positively associated with decrease of PANSS positive symptoms, general psychopathology, and total score (all P < .05). Multiple linear regression analysis showed that baseline weight, decrease of PANSS total score, and sex were significantly associated with weight gain after treatment. CONCLUSIONS: Our findings suggest that there is a significant association between weight gain and improvement of clinical symptoms after 8 weeks of antipsychotic treatment in patients with ANFE schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04076371.

Influence of manganese exposure on cognitive function, plasma APP and Aß levels in older men.

BACKGROUND: Elevated manganese (Mn) exposure impairs cognition in adults and children, but the association between Mn and cognitive function in elderly people is unclear. Previous studies have linked Mn neurotoxicity in AD to Aß-dependent mechanisms. However, the association between Mn and plasma APP and Aß in the general elderly population remains unknown. This study aimed to investigate the association between Mn exposure and cognitive function, plasma APP and plasma Aß in older adults. METHODS: Cognitive abilities in 375 men aged 60 and older in Guangxi, China were assessed using the Mini-Mental State Examination (MMSE) and cognitive impairment were identified using education-stratified cut-off points of MMSE scores. Urinary Mn levels and plasma APP, and Aß levels were measured using ICP-MS and ELISA, respectively. RESULTS: A total of 109 (29.07 %) older men were identified as having cognitive impairment. The median urinary Mn level was 0.22 µg/g creatinine. Urinary Mn levels were negatively correlated with MMSE scores (ß = -1.35, 95 % CI: -2.65 to -0.06; p = 0.041). In addition, higher concentrations of urinary manganese were associated with a greater risk of cognitive impairment (OR = 2.03, 95 % CI: 1.14-3.59; comparing the highest and lowest manganese; p = 0.025). Moreover, plasma APP levels were inversely associated with urinary Mn levels (r = -0.123, p = 0.020), and positively associated with MMSE scores (r = 0.158, p = 0.002). Surprisingly, no correlations were observed between plasma Aß42, Aß40, Aß40/Aß42, or Aß42/Aß40 and urinary Mn levels and MMSE scores. CONCLUSION: These results suggested that Mn exposure is negatively associated with older men's cognition and plasma APP levels, but not plasma Aß levels.

Epidemiological characteristics of 561 cases of intracerebral hemorrhage in Chengdu, China.

ABSTRACT: To explore the epidemiology of patients with spontaneous intracerebral hemorrhage (sICH) in Chengdu, China, we retrieved the data of patients with spontaneous cerebral hemorrhage admitted to the First Affiliated Hospital of Chengdu Medical College from January 2017 to December 2019. We performed a comprehensive analysis of the location of hemorrhage, demographics, factors of hemorrhage, condition of body, severity of disturbance of consciousness, treatment, length of stay (days), inpatient costs, prognosis, and mortality rate in patients with sICH. In total, data of 561 in patients with sICH were included. The hemorrhage site was primarily located in the basal ganglia and thalamus (64.71%). The mean patient age was 63.2 ±â€Š12.4 years (64.17% men, 35.83% women). Male patients (mean age 62.3 ±â€Š12.5 year) were younger than female patients (mean age 64.9 ±â€Š12.1 year). The age of sICH onset in our sample was between 40 and 79 years; this occurred in 87.70% of the included cases. There were more males than females, which may be related to more daily smoking, longer drinking years, and overweight in males than in females. Cases occurred most frequently during the winter and spring months, and the relationship between sICH visits and hospitalizations appeared as a U-shape. The median time from illness onset to hospital admission was 3.0 hours. According to the Glasgow Coma Scale (GCS) score at admission, 20.50% of sICH cases were of mild intensity, 39.93% were moderate, and 39.57% were severe. Moderate disorder is the most common sICH severity. Factors influencing the disturbance of consciousness were blood glucose level at the time of admission as well as the number of years with hypertension. The lower the degree of disturbance of consciousness and the more they smoked per day indicated they had a higher likelihood of receiving surgical treatment while in hospital. The median hospital stay was 13.0 days, while the median inpatient cost was USD 3609. The 30-day mortality rate was 18.36%. sICH is an important public health problem in Chengdu, China. A governmental initiative is urgently needed to establish a sICH monitoring system that covers the Chengdu region to develop more effective and targeted measures for sICH prevention, treatment, and rehabilitation.

IRGM promotes melanoma cell survival through autophagy and is a promising prognostic biomarker for clinical application.

Previously, we showed that mouse immunity-related guanosine triphosphatase (GTPase) family M protein 1 (Irgm1) promotes malignant melanoma progression by inducing cellular autophagy flux and metastasis. Human IRGM, a truncated protein functionally distinct from its mouse counterpart, has several splice isoforms. In this study, we analyzed the association of IRGM and human melanoma clinical prognosis and investigated the function of IRGM in human melanoma cells. Data from the training cohort (n = 144) showed that overexpression of IRGM is proportional to melanoma genesis and clinical stages in human tissue chips. A validation cohort (n = 78) further confirmed that IRGM is an independent risk factor promoting melanoma progression and is associated with poor survival of patients. Among IRGM isoforms, we found that IRGMb is responsible for such correlation. In addition, IRGM promoted melanoma cell survival through autophagy, both in vitro and in vivo. We further showed that the blockade of translocation of high-mobility group box 1 (HMGB1) from the nucleus to cytoplasm inhibits IRGM1-mediated cellular autophagy and reduces cell survival. IRGM functions as a positive regulator of melanoma progression through autophagy and may serve as a promising prognostic marker and therapeutic target.

IRGM promotes the PINK1-mediated mitophagy through the degradation of Mitofilin in SH-SY5Y cells.

Mitochondria is a double membrane-bound cellular organelle that generates energy to maintain the homeostasis of cells. Immunity-related GTPase M (IRGM) in human locates at the inner membrane of mitochondria and is best known for its role in regulating autophagy against intracellular pathogens. Previous studies have shown that IRGM is crucial for the normal function of mitochondria, yet, the molecular mechanisms underlying IRGM-mediated quality control of mitochondria are still not fully understood. In this study, we showed that knocking-down IRGM inhibits CCCP induced mitophagy in SH-SY5Y cells. Furthermore, we reported that IRGM decreases the stability of Mitofilin (IMMT, MIC60) in the damaged mitochondria. Knocking down Mitofilin rescues the loss of mitophagy that is observed in the IRGM KD cells, suggesting that IRGM regulates mitophagy through the inhibition of Mitofilin. These data together provide molecular insight regarding how IRGM regulates mitophagy to control the quality of mitochondria.