Objective This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression (n = 113,154) and MDD (n = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that SLC6A4, GRIN2A, GRIN2C, SCN10A, and IL1B expression are associated with an increased risk of depression. In contrast, ADRB1, CHRNA3, HTR3A, GSTP1, and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.

Objective To investigate the effects of glutathiones-transferase (GST) T1, GSTM1 and epoxide hydrolase (EPHX1) genes on skin injury in workers exposed to coal tar pitch. Methods Workers from a carbon manufacturing company involved in coal tar pitch production and use were selected as the study subjects using a judgment sampling method. Workers with skin injury after exposed to coal tar were selected as the case group (55 cases), and those with the same workshop and type of work but without skin abnormalities were selected as the control group (197 cases). Urine and blood samples were collected from the workers, and levels of polycyclic aromatic hydrocarbon metabolites, including 1-pyrenol (1-OH-P), 1-naphthol (1-OH-N) and 2-naphthol (2-OH-N), in urine were measured using ultra high-performance liquid chromatography tandem mass spectrometry. The GSTT1, GSTM1 and EPHX1 genes in blood were detected by polymerase chain reaction. Results In the case group, all 55 workers reported skin stinging, 25 workers reported itching and flaking, and 15 workers reported blackheads and pigmentation. Urinary levels of 1-OH-N and 2-OH-N were lower in the worker in the case group than that in the control group (all P<0.05). However, there was no significant difference in the level of 1-OH-P between the two groups (P>0.05). There were significant differences in the number of workers with GSTT1, GSTM1 and EPHX1(His139His) genes between the two groups (all P<0.01). The GSTT1 and GSTM1 genes were positively correlated with post-shift urinary levels of 1-OH-N, 1-OH-P, and 2-OH-N (all P<0.01). The EPHX1 (139Arg locus) gene was positively correlated with post-shift 2-OH-N levels (P=0.03). The GSTT1, GSTM1, and EPHX1 (139Arg locus) genes were associated with reduced skin damage among coal tar workers (all P<0.01), after controlling for age, length of service, gender, smoking, and alcohol consumption. Conclusion Exposure to coal tar pitch can cause skin injury in workers, and the GSTT1, GSTM1, and EPHX1 (139Arg locus) genes are protective factors against skin injury in those workers.

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.
Rats ; Male ; Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Sterol Regulatory Element Binding Protein 1/metabolism* ; Diet, High-Fat/adverse effects* ; Diosgenin/metabolism* ; Chaperonin 60/therapeutic use* ; Rats, Sprague-Dawley ; Liver ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Triglycerides ; RNA, Messenger/metabolism* ; Simvastatin/therapeutic use* ; Body Weight ; Lipid Metabolism ; Mammals/metabolism*

【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective To analyze the epidemic characteristics of tuberculosis in Zibo City in recent years, and to provide a scientific basis for the formulation of tuberculosis prevention and control strategies and measures during the 14th Five-Year Plan period. Methods Descriptive epidemiological analysis was used to analyze the information of tuberculosis patients registered in ^“China Disease Control and Prevention Information System-Tuberculosis Information System^” from 2012 to 2020 in Zibo City. Results From 2012 to 2020, a total of 12,706 pulmonary tuberculosis patients were registered in Zibo City, and the registered incidence rate decreased year by year (F=53.348, P<0.001), with an average annual rate of 30.45/10 million. There was no significant change in mortality. In regional distribution, the incidence was higher in northern region of Zibo than that in the southern region, with a cross distribution in the central region. In terms of time distribution, there were cases in each month over the years, and the overall trend increased first, then decreased and once again increased (F=8.856, P=0.006<0.01), with two low points occurring between January to February and also in October, and two peaks occurring between May to June and also in December. In terms of population distribution, most patients were local cases (82.38%). The incidence rate of males was about 2.09 times that of females. The incidence rate of children aged 0-14 was the lowest, while elderly people aged 65 years old and over had the highest incidence (61.02/10 million). Farmers were the main occupation among tuberculosis cases, accounting for 60.59% of the total. The main source of patients was from tracking, accounting for more than 50% since 2016. Conclusion The epidemic of tuberculosis in Zibo is stable and the incidence rate is decreasing year by year, showing seasonal variations. The majority of the patients are male. Special attention should be paid to farmers and the elderly, and further research on risk factors in high-risk areas and counties should be strengthened.

Inducing durable and effective immunity against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) via vaccination is essential to combat the current pandemic of coronavirus disease 2019 (COVID-19). It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time, which calls for an additional vaccination regime, as known as booster immunization, to restore immunity among previously vaccinated populations. Here we report a pilot open-label trial of a third dose of BBIBP-CorV, an inactivated SARS-CoV-2 vaccine (Vero cell), on 136 participants aged between 18 to 63 years. Safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day 28. While systemic reactogenicity was either absent or mild, SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks, surpassing the peak antibody titers elicited by the initial two-dose immunization regime. Broad increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third vaccination. Furthermore, in an exploratory study, a newly developed recombinant protein vaccine, NVSI-06-08 (CHO Cells), was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed individuals. Together, these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity, providing support for further trials of booster vaccination in larger populations.
Adolescent ; Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; China ; Humans ; Immunogenicity, Vaccine ; Middle Aged ; SARS-CoV-2 ; Vaccination ; Young Adult

Objective To evaluate and analyze the feasibility and application effect of ^“DOTS + WeChat^” in the treatment and management of tuberculosis patients. Methods From 2018 to 2019, a total of 2 420 active pulmonary tuberculosis patients were registered in Zibo City, and 1 988 patients meeting the inclusion criteria were selected as the research subjects. 836 patients were randomly enrolled under the ^“DOTS + WeChat^” integrated management mode, while the other 1152 cases were treated with single DOTS management mode. The regular medication status, treatment and outcome, and core knowledge awareness of the two groups were analyzed by SPSS16.0 software, χ²- test and t- test methods. Result The ^“DOTS + WeChat^” comprehensive management group had higher a regular medication rate (98.80%), coincidence rate of sputum test times (95.81%), and success rate of treatment (98.68%) than the single DOTS management group (92.10%, 90.19%, and 96.53%) (P=0.000, 0.000, 0.003). The rate of medical staff participating in supervision and management in the comprehensive management group (100%) was higher than that in the single management group (75.87%) (P=0.000). The complete follow-up rate in the consolidation period (100%) and the complete whole course follow-up rate (99.76%) were both higher than those in the single management group (P=0.000, 0.001). The awareness level of core knowledge in the comprehensive management group (78.58±4.32) was higher than that in the single management group (70.70±8.02) (P=0.000). Conclusion The application of WeChat management mode has a positive effect on the treatment and management of tuberculosis patients in Zibo City. It is a feasible and effective supplement and improvement to the current tuberculosis control and management measures, which is worthy of further promotion and exploration.

To investigate the expression of small dense low-density lipoprotein cholesterol (sdLDL-C) in patients with H-type hypertension and its association with H-type hypertension and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. The retrospective study method was used,and a total of 207 hospitalized hypertensive patients (76 males and 131 females, aged 40-82 years, median age 66 years) admitted to the Zibo First Hospital from March 2021 to March 2022 were enrolled in this study. The levels of homocysteine (Hcy), sdLDL-C, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein (a) [Lp(a)] were measured. The patients were divided into H-type hypertensive group (n=105, 40 males and 65 females) and non-H-type hypertensive group (n=102, 36 males and 66 females) according to Hcy levels. The C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene was detected in each group. Logistic regression analysis was performed for the related factors of H-type hypertension. The serum sdLDL-C levels were (0.92±0.31) and (0.65±0.28) mmol/L in H-type hypertension group and non-H-type hypertension group, respectively. The sdLDL-C levels in H-type hypertension group were significantly higher than those in non-H-type hypertension group (t=6.500, P<0.01). There was no significant difference in the serum sdLDL-C levels between males and females in H-type hypertension group (t=-1.543, P=0.129). The CC, CT, TT genotypes and C and T allele frequencies of MTHFR C677T in H-type hypertension group were significantly different from those in non-H-type hypertension group (P<0.05). The Hcy and sdLDL-C levels in different genotypes of MTHFR in H-type hypertension group were significantly different (H=12.742, P=0.002; F=3.345, P=0.042). Among them, Hcy levels were higher in TT genotype than in CT and CC genotypes, respectively (Z=-28.099, P=0.003; Z=-16.112, P=0.040), and sdLDL-C levels were higher in TT genotype than in CC genotype (t=-2.587, P=0.012). Logistic regression analysis showed that age, sdLDL-C, and MTHFRC677T TT genotypes were associated with the development for H-type hypertension. In conclusion, the level of sdLDL-C is associated with MTHFR gene polymorphisms and may be associated with the development of H-type hypertension.
Male ; Female ; Humans ; Aged ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Cholesterol, LDL/genetics* ; Retrospective Studies ; Polymorphism, Genetic ; Gene Frequency ; Genotype ; Hypertension ; Homocysteine/genetics*

【Objective】 To learn the production efficient of platelet components among prefecture-level blood stations in China, to provide supporting data for those blood stations to optimize the production mode of platelet components and continuously improve production efficiency and supply capacity. 【Methods】 The data from 2017 to 2020 was obtained from 24 prefecture-level blood stations who were the members of the practice comparison network for blood institutes in China. The collection units of apheresis platelets, the number of dual-collections of apheresis platelets and plasma, the average apheresis units of one platelet apheresis procedure, the discarded rate of apheresis platelets, the amount of expired apheresis platelets and the amount of apheresis platelets issued were collected. For concentrated platelets, the prepared amount of platelet concentrates and the amount of expired platelet concentrates were collected; both the quantity of qualified and issued concentrated platelets were submitted for statistical analysis.The total output and efficiency of platelet components were calculated based on the collected data. 【Results】 The average annual growth rate of apheresis platelets collection in 24 prefecture-level blood stations was 12.23%, accounting for 99.80% of the total platelet output; the average collection unit of one platelets apheresis procedure was 1.75; from 2019 to 2020, only 5 blood stations performed dual-collection of platelet and plasma during one apheresis procedure; the discarded rate of apheresis platelets was 0.28%, of which 0.007% was due to expiration. A total of 1 621.2 therapeutic units of concentrated platelets were prepared, and 13.03% of them was discarded due to the expiration. The production efficiency of platelet components was 97.56%, of which the production efficiency of apheresis platelets was 97.61% and the production efficiency of concentrated platelets was 74.43%. 【Conclusion】 There are large regional differences in the supply capacity of platelet components in prefecture-level blood stations. Apheresis platelets are the main resource of platelet components product, and the collection capacity is increasing over the years with the characteristics of high production efficiency and low expiration scrapping rate. However, the preparation of concentrated platelets are still limited with relatively low production and high expiration discarded rate.