Causal roles of educational duration in bone mineral density and risk factors for osteoporosis: a Mendelian randomization study.

BACKGROUND: Educational duration might play a vital role in preventing the occurrence and development of osteoporosis(OP). PURPOSE: To assess the causal effect of educational duration on bone mineral density(BMD) and risk factors for OP by Mendelian randomization(MR) study. METHODS: The causal relationship was analyzed using data from genome-wide association study(GWAS). Inverse variance weighting (IVW) was used as the main analysis method. Horizontal pleiotropy was identified by MR-Egger intercept test, MR pleiotropy residual sum and outlier (MR-PRESSO) test. The leave-one-out method was used as a sensitivity analysis. RESULTS: The IVW results indicated that there was a positive causal relationship between educational duration and BMD (OR = 1.012, 95%CI:1.003-1.022), physical activity(PA) (OR = 1.156, 95%CI:1.032-1.295), calcium consumption (OR = 1.004, 95%CI:1.002-1.005), and coffee intake (OR = 1.019, 95%CI:1.014-1.024). There was a negative association between whole body fat mass (OR = 0.950, 95%CI:0.939-0.961), time for vigorous PA (OR = 0.955, 95%CI:0.939-0.972), sunbath (OR = 0.987, 95%CI:0.986-0.989), salt consumption (OR = 0.965, 95%CI:0.959-0.971), fizzy drink intake (OR = 0.985, 95%CI:0.978-0.992), smoking (OR = 0.969, 95%CI:0.964-0.975), and falling risk (OR = 0.976, 95%CI:0.965-0.987). There was no significant association between educational duration and lean mass, time for light-to-moderate PA, milk intake, and alcohol intake. Horizontal pleiotropy was absent in this study. The results were robust under sensitivity analyses. CONCLUSION: A longer educational duration was causally linked with increased BMD. No causal relationship had been found between educational duration and lean mass, time for light-to-moderate PA, milk intake, and alcohol consumption as risk factors for osteoporosis.

Pyroptosis and polarization of macrophages in septic acute lung injury induced by lipopolysaccharide in mice.

BACKGROUND: Pyroptosis and polarization are significant contributors to the onset and development of many diseases. At present, the relationship between pyroptosis and polarization in acute lung injury (ALI) caused by sepsis remains unclear. METHODS: The ALI model for sepsis was created in mice and categorized into the blank control, lipopolysaccharide (LPS) group, LPS + low-dose Belnacasan group, LPS + high-dose Belnacasan group, LPS + low-dose Wedelolactone group, LPS + high-dose Wedelolactone group, and positive control group. The wet-dry specific gravity was evaluated to compare pulmonary edema. Hematoxylin-eosin, Masson, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining techniques were conducted to observe and contrast the pathological changes in lung tissue. ELISA was utilized to identify M1 and M2 macrophages and correlated inflammatory factors. Immunohistochemical staining and flow cytometry were employed to identify markers of M1 and M2 macrophages in lung tissue. Propidium iodide staining, together with flow cytometry, was utilized to observe the degree and positive rate of pyroptosis of alveolar macrophages. Western blot analysis was conducted to detect the expression levels of Caspase 1, Caspase 11, GSDMD, and IL-18 in the lung tissues of each group. The real-time quantitative polymerase chain reaction method was used to ascertain relative expression levels of NLRP3, Caspase 1, Caspase 11, GSDMD, IL-18, iNOS, and Arg-1 in lung tissues of all groups. RESULTS: In mice with sepsis-induced ALI, both classical and nonclassical pathways of pyroptosis are observed. Inhibiting pyroptosis has been found to ameliorate lung injury, pulmonary edema, and inflammation induced by LPS. Notably, the expression of NLRP3, Caspase 1, Caspase 11, GSDMD, IL-1ß, IL-18, TGF-ß, CD86, CD206, iNOS, and Arg-1 were all altered in this process. Additionally, alveolar macrophages were polarized along with pyroptosis in mice with ALI caused by sepsis. CONCLUSION: Pyroptosis of alveolar macrophages in the context of ALI in mice infected with sepsis has been linked to the polarization of alveolar macrophages toward type M1.

CAUSAL ROLES OF SERUM URIC ACID LEVELS AND GOUT IN SEPSIS: A MENDELIAN RANDOMIZATION STUDY.

ABSTRACT: Objective: Several epidemiological studies have identified a potential link between serum uric acid (UA), gout, and sepsis. The primary objective of this study is to delve deeper into this connection, investigating the causal effect of UA and gout on sepsis by applying Mendelian randomization (MR). Methods: The causal relationship was analyzed using data from Genome-Wide Association Study (GWAS). Inverse variance weighting (IVW) was used as the main analysis method. Three complementary methods were used for our MR analysis, which included the MR-Egger regression method, the weighted median method, the simple median method. Horizontal pleiotropy was identified by MR-Egger intercept test. Cochran's Q statistics were employed to assess the existence of instrument heterogeneity. The leave-one-out method was used as a sensitivity analysis. Results: The IVW results indicated that there was a positive causal relationship between UA and sepsis (critical care) (odds ratio [OR] = 0.24, 95% confidence interval [CI]: 0.04 to 0.43, P = 0.018, F = 4,291.20). There was no significant association between UA and sepsis (28-day death in critical care) (OR = 0.10, 95% CI = -0.29 to 0.50, P = 0.604). There was no significant association between gout and sepsis (critical care) (OR = 0.85, 95% CI = -4.87 to 6.57, P = 0.771), and sepsis (28-day death in critical care) (OR = -6.30, 95% CI = -17.41 to 4.81, P = 0.267). Horizontal pleiotropy was absent in this study. The results were robust under all sensitivity analyses. Conclusion: The study revealed that elevated UA levels were causally linked with sepsis (critical care). No causal relationship had been found between UA and sepsis (28-day death in critical care), as well as between gout and sepsis.

Challenges and opportunities in animal models of psoriatic arthritis.

OBJECTIVE: To review the preparation, characteristics and research progress of different PsA animal models. METHODS: Computerized searches were conducted in CNKI, PubMed and other databases to classify and discuss the relevant studies on PsA animal models. The search keywords were "PsA and animal model(s), PsA and animal(s), PsA and mouse, PsA and mice, PsA and rat(s), PsA and rabbit(s), PsA and dog(s)" RESULTS: The experimental animals currently used to study PsA are mainly rodents, including mice and rats. According to the different methods of preparing the models, the retrieved animal models were classified into spontaneous or genetic mutation, transgenic and induced animal models. These PsA animal models involve multiple pathogenesis, some experimental animals' lesions appear in a short and comprehensive cycle, some have a high success rate in molding, and some are complex and less reproducibility. This article summarizes the preparation methods, advantages and disadvantages of different models. CONCLUSIONS: The animal models of PsA aim to mimic the clinicopathological alterations of PsA patients through gene mutation, transgenesis or targeted proinflammatory factor and to reveal new pathogenic pathways and therapeutic targets by exploring the pathological features and clinical manifestations of the disease. This work will have very far-reaching implications for the in-depth understanding of PsA and the development of new drugs.

Efficacy and safety of COVID-19 inactivated vaccine: A meta-analysis.

Background: Inactivated vaccine is one of the primary technology types of Coronavirus Disease 2019 (COVID-19) vaccines, which has wide application in many countries, including mainland China. However, systematic evaluation of the efficacy and safety of COVID-19 inactivated vaccines remains limited. And trust in the vaccine is the key to solving vaccine hesitancy. Methods: Various academic databases were searched comprehensively for randomized controlled trials (RCTs) related to COVID-19 inactivated vaccines. The deadline for retrieval was December 2021. Study screening and data extraction were according to inclusive and exclusive criteria. Statistical analyses were performed using RevMan software 5.3 version and STATA software 16.0 version. Results: Eight studies with 79,334 subjects were included of which 48,123 had received two doses of COVID-19 inactivated vaccines, and 31,211 had received two doses of placebo. The results of the meta-analysis showed that: in terms of effectiveness evaluation, two doses of COVID-19 inactivated vaccines decreased the symptomatic infection [relative risk (RR) = 0.23, 95% confidence interval (CI) (0.18,0.30), P < 0.00001], asymptomatic infection [RR = 0.48, 95%CI (0.32, 0.74), P = 0.0008], total infection [RR = 0.32, 95%CI (0.24, 0.41), P < 0.00001] and hospitalization [RR = 0.06, 95%CI (0.01, 0.27), P = 0.0002] for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) significantly. In terms of safety assessment, two doses of COVID-19 inactivated vaccines also caused more adverse events. After two inoculations, total adverse events and systemic adverse events increased significantly [total adverse events RR = 1.14, 95%CI (1.08, 1.21), P < 0.00001; systemic adverse events RR = 1.22, 95%CI (1.09, 1.35), P = 0.0002]. The most common adverse event was pain at the injection site. Almost all local adverse reactions consisted of these events. The incidence of pain at the injection site was related to adjuvants. Using aluminum hydroxide as an adjuvant increased local pain significantly [RR = 1.97, 95%CI (1.52, 2.55), P < 0.00001]. Two doses COVID-19 inactivated vaccines did not increase serious adverse events [RR = 0.71, 95%CI (0.57, 0.90), P = 0.004]. Conclusion: Two doses of inactivated COVID-19 vaccines in people over 18 years of age effectively prevented SARS-CoV-2 infection and its associated hospitalizations. Short-term, mild to moderate adverse reactions had occurred, but serious adverse events were rare. No placebo or vaccine-related deaths had been reported. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: 42021291250.

Influence of rs1746048 SNPs on clinical manifestations and incidence of acute myocardial infarction in Guangxi Han population.

A relationship of the CXCL12 gene rs1746048 SNPs with AMI has been reported in American, European, Caucasian, and Pakistani populations. However, little is known about this association in the Guangxi Han population. In this study, we detect associations between rs1746048 SNPs and susceptibility, risk factors, clinical characteristics, and gene-environment interactions for AMI. 300 AMI patients and 300 healthy controls of Chinese Han were enrolled. Genotyping of rs1746048 SNPs was performed using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and then confirmed by direct sequencing. Significant differences in both genotypic and allelic frequencies of rs1746048 SNPs between AMI and the control group were not detected (P > 0.05 for each). The frequency of CC genotypes of rs1746048 SNPs was the highest in the 2 h < DT ≤ 6 h subgroup (P < 0.05). The frequencies of the CT genotype and the T allele were significantly higher in the severe complications subgroup of AMI (P < 0.05). There were interactions between the subjects with rs1746048 SNPs and smoking or alcohol consumption (P < 0.017 for each). Rs1746048 SNPs were not correlated with the risk of AMI in present study. For the first time, we discovered that the CC genotype of the rs1746048 SNPs was significantly correlated with DT of AMI; the frequencies of the CT genotype and the minor T allele were positively correlated with the severe complications of AMI. Also, the interaction between the rs1746048 SNPs and smoking or alcohol appears to increase the risk of AMI exposure.

The successful treatment of systemic toxic induced paraquat poisoning by skin absorption: case reports and a literature review.

Paraquat (PQ) poisoning is life-threatening, can cause acute organ damage, and has a high mortality. However, cases of skin absorption induced by PQ poisoning are rare. This report describes a case where PQ was absorbed by the patient's skin, causing severe organ damage. Having accidentally touched PQ on his skin, the patient, whose skin festered, became damaged, red, and swollen, developed serious systemic toxic symptoms. The patient recovered after systemic treatment. Generally speaking, being poisoned by PQ through skin absorption is rare. By analyzing the reported PQ poisoning through skin absorption and by reviewing the relevant literature, this paper aims to explore successful treatments for PQ poisoning through skin absorption and to provide treatment guidance for physicians encountering such cases.

Graphene oxide regulates endoplasmic reticulum stress: autophagic pathways in nasopharyngeal carcinoma cells.

During carcinogenesis, growth, proliferation, invasion and metastasis, increasing evidence shows that autophagy and endoplasmic reticulum stress (ER stress) are regulated in nasopharyngeal carcinoma, a finding drawing more attention from physicians and scientists. As one of the carbon-based nano-materials, graphene oxide (GO) has been extensively used for its advantages, such as biocompatibility, an ultrahigh surface to volume ratio, abundant surface groups, and a special photothermal effect. The present study is designed to explore the effects of GO on autophagy and ER stress in nasopharyngeal carcinoma cells. Our findings will provide scientific bases for the clinical application of GO and the development of new analogues. GO inhibits the proliferation of HONE1 cells, promotes their apoptosis in a concentration-dependent manner and enhances the expression of the ER stress chaperone GRP78 in HONE1 cells. These results suggest that GO could affect HONE1 cells through the autophagic and ER stress pathways. Thus, GO inhibits the proliferation of nasopharyngeal carcinoma cells via the induction of cytotoxic autophagy. In addition, ER stress is also activated as an adaptive response, so blocking ER stress may enhance the sensitivity of nasopharyngeal carcinoma cells to GO.

Elevated levels of von Willebrand factor and high mobility group box 1 (HMGB1) are associated with disease severity and clinical outcome of scrub typhus.

OBJECTIVES: This study aimed to investigate whether von Willebrand factor (vWF) and high mobility group box 1 (HMGB1) are associated with the severity and clinical outcome of scrub typhus and to seek novel biomarkers for surveillance and prediction of the prognosis of this infection. METHODS: Serum concentrations of vWF and HMGB1 were measured twice by ELISA for scrub typhus patients (n=103), once prior to doxycycline therapy and then on day 7 of doxycycline therapy; concentrations were measured once for healthy controls (n=32). RESULTS: Among the total 103 patients enrolled, 38 had disease complicated by multiple organ dysfunction syndrome (MODS). Serum concentrations of vWF and HMGB1 were significantly higher in all the patients than in the healthy controls, both prior to doxycycline treatment and on day 7 of doxycycline treatment (p<0.01). Furthermore, serum levels of vWF, HMGB1, and creatinine (SCr) in the patients with MODS increased distinctly, while the platelet (PLT) count diminished markedly compared to the levels in patients without MODS (p<0.01). The concentration of vWF was positively correlated with that of HMGB1 (r=0.764, p<0.001) and SCr (r=0.528, p<0.001), but negatively correlated with the PLT count (r=-0.632, p<0.001). Both HMGB1 and vWF were significantly associated with mortality in scrub typhus (area under the curve (AUC)=0.864, p=0.001, and AUC=0.862, p=0.001, respectively). CONCLUSIONS: Elevated levels of vWF and HMGB1 are associated with the severity and clinical outcome of scrub typhus. These represent possible new biomarkers for use in the assessment and prognostic prediction of this infection.

[Effect and mechanism of methyl protodioscin in protecting cardiomyocytes against anoxia/reoxygenation injury].

OBJECTIVE: To study the effect and mechanism of methyl protodioscin (MPD), an active ingredients of yamogenin, in protecting cardiomyocytes (CMC) against anoxia/reoxygenation (A/R) injury. METHODS: Cultured CMCs of neonatal SD rats were randomly divided into three groups, cells in Group A were untreated normal cells, cells in Group B and C were made to injury CMC model by A/R, and only those in Group C were treated with MPD. Levels of ATPase activity and lactate dehydrogenase (LDH) in cell membrane of CMCs were determined. Besides, the mRNA expression of sodium-calcium exchanger (NCX) in MPD treated CMCs was detected. RESULTS: As compared with Group B, the degree of CMC injury was significantly milder and the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase were higher in Group C after cells were treated with MPD in concentration of 10 microg/mL and 50 microg/mL. The mRNA expression of NCX in CMCs was down-regulated after MPD treatment (P < 0.05). CONCLUSION: MPD could maintain the low calcium internal environment in CMCs by way of protecting the membranous function of Na+ -pump and Ca2+ -pump, and influencing the Ca2+ transmembrane transportation in CMCs.

[Effects of methyl protodioscin on [Ca2+]i and ATPase activity in cardiomyocytes and analysis of mechanisms].

OBJECTIVE: To study the effects of methyl protodioscin on the [Ca2+]i and the ATPase activity in cardiomyocytes, as well as their mechanisms. METHOD: The cardiomyocytes were randomly divided into three groups, the control group treated with no serumal DMEM, the MPD group treated with MPD and the dilthiazem group treated with dilthiazem. Fluorospectrophotometer was used to determined the level of myocardial cell intracellular Ca2+ [Ca2+]i. In the experiment of ATPase activity on cellular membrane, the cardiomyocytes were randomly divided into two groups, the control group treated with no serumal DMEM, the MPD group treated with MPD. The activity of Na+-K+-ATPase,Ca2+-Mg2+-ATPase and Mg2+-ATP ATPase were determined. The quantitative analysis of SERCA2a mRNA expression was studied by RT-PCR that the groups and treatments in cardiomyocytes same as the experiment for ATPase activity assay. RESULT: Under the quiescent condition, compared to the control group, the level of [Ca2+]i in cardiomyocytes of the MPD group and dilthiazem group was no different. After treatment with 40 mmol x L(-1) KCl, [Ca2+] was significantly lower in the MPD group and the dilthiazem group, and the intensity of peak value in time course of 60 s, the dilthiazem group and the MPD group also were lower than the control group (P < 0.001). Ca2+-Mg2+-ATPase and Na+-K+-ATPase in cultured rat were increased after treated with MPD compared to treatment with no serumal DMEM (P < 0.05, P < 0.01), but Mg2+-ATPase in these groups had no different. The expression of SERCA2a mRNA between the MPD group and the control group was no different. MPD could not up-regulated or down-regulated SERCA2a in endocytoplasmic reticulum. CONCLUSION: Methyl protodioscin could block the volt dependent form calcium channel in cellular membrane, and up-regulate the function of sodium pump and calcium pump, so that it could remain low calcium in the internal environment in cardiomyocytes.

[Effects of Panax notoginseng saponins on long-term potentiation in the CA1 region of the rat hippocampus].

Panax notoginseng saponins (PNS) are very important extracts from roots of medicinal herb Sanchi Ginseng which is highly regarded in China for its therapeutic ability to meliorate blood-circulation, anti-anoxia, improve memory, and anti-caducity effects. In this study, we used blind whole-cell voltage-clamp recordings to detect the effects of PNS on long-term potentiation (LTP) in the CA1 region of the hippocampus, and investigated the electrophysiological mechanisms underlying potentiating effects of PNS on learning and memory. Wistar rats (3-4 weeks) were decapitated and hippocampal slices (400 microm thick) were cut coronally. Excitatory postsynaptic currents (EPSCs) were recorded by patch clamp technique in whole-cell configuration. The Schaffer collateral/commissural pathway was stimulated by high frequency stimulation (HFS: 100 Hz) pulses to induce LTP. The findings showed that 0.1 - 0.4 g x L(-1) PNS significantly depressed the amplitude of EPSCs (P < 0.05) and had no facilitative effects on LTP of pyramidal neurons located in the CA1 region. PNS in the concentrations of 0.04 - 0.05 g x L(-1) did not appreciably affect the amplitude of EPSCs (P > 0.05) but markedly increased the amplitude of LTP (P < 0.05). In conclusion, 0.04 - 0.05 g x L(-1) PNS could facilitate LTP in the CA1 region of the rat hippocampus and it is reasonable to suggest that this action may contribute to its potentiating effects on learning and memory.

Expression of HBsAg,Fas and PCNA in hepatocellular carcinoma and their significance in understanding HBV related hepatocarcinogenesis / 中国现代普通外科进展

Objective:To investigate the expressive characters and their significance by detecting the expressions of HBsAg,Fas and proliferating cell nuclear antigen(PCNA) in both hepatocellular carcinoma(HCC) and their surrounding non-cancerous tissues.The correlation between HBV infection and HCC,and the possible mechanism of hepatocellular carcinogenesis were discussed.Methods:HBsAg,Fas and PCNA were detected by immunohistochemistry from 52 cases of hepatocellular carcinoma as well as 42 corresponding non-cancerous tissues.Clinical data suchas serum AFP levels was also analysed.Results:Both HBsAg and Fas were strongly expressed in non-cancerous tissues,with positive rate of each achieving 78.6%.However their expression rates in cancer tissues were 21.2% and 30.8% respectively,significantly lower and less intensive than that of their corresponding non-cancerous ones(P