Laparoscopic total mesorectal excision versus transanal total mesorectal excision for mid and low rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic total mesorectal excision (LaTME) and transanal total mesorectal excision (TaTME) are popular mid and low rectal cancer trends. However, there is currently no systematic comparison between LaTME and TaTME of mid and low rectal cancer. Therefore, we systematically study the perioperative and pathological outcomes of LaTME and TaTME in mid and low rectal cancer. METHODS: Articles included searching through the Embase, Cochrane Library, PubMed, Medline, and Web of science for articles on LaTME and TaTME. We calculated pooled standard mean difference (SMD), relative risk (RR), and 95% confidence intervals (CIs). The protocol for this review has been registered on PROSPERO (CRD42022380067). RESULTS: There are 8761 participants included in 33 articles. Compared with TaTME, patients who underwent LaTME had no statistical difference in operation time (OP), estimated blood loss (EBL), postoperative hospital stay, over complications, intraoperative complications, postoperative complications, anastomotic stenosis, wound infection, circumferential resection margin, distal resection margin, major low anterior resection syndrom, lymph node yield, loop ileostomy, and diverting ileostomy. There are similarities between LaTME and TaTME for 2-year DFS rate, 2-year OS rate, distant metastasis rat, and local recurrence rate. However, patients who underwent LaTME had less anastomotic leak rates (RR 0.82; 95% CI: 0.70-0.97; I2 = 10.6%, P = .019) but TaTME had less end colostomy (RR 1.96; 95% CI: 1.19-3.23; I2 = 0%, P = .008). CONCLUSION: This study comprehensively and systematically evaluated the differences in safety and effectiveness between LaTME and TaTME in the treatment of mid and low rectal cancer through meta-analysis. Patients who underwent LaTME had less anastomotic leak rate but TaTME had less end colostomy. There is no difference in other aspects. Of course, in the future, more scientific and rigorous conclusions need to be drawn from multi-center RCT research.

Impacts of cadmium on mouse neural stem cells based on dose-response metabomics / 环境与职业医学

Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl2 at designed doses (0, 0.5, 1.0, and 1.5 μmol·L−1). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L−1 dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.

Determination of the ELISA kits for screening convalescence plasma with high potency of SARS-CoV-2 IgG / 中国输血杂志

【Objective】 To determine the ELISA kit for screening convalescence plasma with high potency of SARS-CoV-2 IgG by comparing and analyzing the plasma detection results of convalescent plasma collected in different periods via ELISA kits from two manufacturers and the results of mixed plasma with different potency via pseudovirus neutralization experiments. 【Methods】 Two ELISA kits from different manufacturers(named A, B) were used to detect the plasma of 269 convalescent patients collected from Feb.2020~Jan.2022. The correlation and concordance rate of the two results were analyzed to determine the kit preliminarily. According to the titers of diluted series of standard of the preliminary selected kit, 5 mixed plasma samples (G4-G128) with different potency were prepared. The correlation of ELISA IgG results of product A/B, as well as the pseudovirus neutralization test of the original strain, Omicron mutant BA.1 and BA.2 strains were analyzed. Combined with the outside-well dilution mode of the strongly positive samples, the kit for high potency of SARS-CoV-2 IgG screening was determined. 【Results】 When the internal control reference B2 was used as the standard, the detection sensitivity of product A and B was 1∶32 vs 1∶8; the detection sensitivity of product A was 4 times that of product B. The correlation Pearson r between the results given by two kits was 0.944 1(P<0.000 1). Product B with low sensitivity was primarily selected as an alternative kit. The ELISA IgG results of samples from mixed plasma showed that the order of correlation r between product A and B was 0.988. The correlation r between product A and neutralization antibody potency of the three viruses was original strain (0.978)>BA.2(0.970)>BA.1(0.799); the order of correlation r between ELISA IgG results of product B and neutralization antibody potency of the three viruses was original strain(0.994)>BA.2(0.968)>BA.1(0.804). If twice-diluted B2 was taken as the excellent standard, 55.4% of product B met the criterion, while 47.2% of product A met.For positive plasma with high IgG potency, the product B kit required a lower dilution of the sample, which was more convenient to operate. 【Conclusion】 Both of the ELISA IgG kit from product A and B can be used to screen IgG antibodies of SARS-CoV-2, while product B is more suitable for screening positive plasma with high IgG potency.

Changes and distribution of antibodies in plasma before and after infection of SARS-CoV-2 Omicron strain / 中国输血杂志

【Objective】 To determine the best collection time period of plasma which can be used for human COVID-19 immunoglobulin for intravenous injection through SARS-CoV-2-IgG change and neutralizing antibody distribution against different virus strain in representative mixed plasma before and after Omicron strain infection by ELISA and pseudovirus neutralization test. 【Methods】 An ELISA method for quantitative detection of SARS-CoV-2-IgG was established and its linear range,accuracy and precision was verified. SARS-CoV-2-IgG potency was detected in 25 convalescent plasma which were collected 20-40 days after confirmed Omicron infection, two groups of mixed plasma samples WP1 and WP2 were prepared according to the SARS-CoV-2-IgG results, and pseudovirus neutralization experiments with different virus strain (prototype strain, BA. 1,BA.2, BA.4/5, BF.7, BQ.1.1) were carried out to determine the distribution of neutralizing antibodies against different virus strain. SARS-CoV-2-IgG potency of representative mixed plasma collected from 14 plasma stations subordinate to the company before and after Omicron strain infection was detected, including Omicron convalescent plasma (OP) collected from different plasma stations from December 2022 to May 2023 and normal pool plasma (VN) feed in March 2023 which collected from March 2022 to December 2022. According to the results, the difference and the change rule with time of SARS-CoV-2-IgG before and after Omicron strain infection were analyzed. 【Results】 The linearity of SARS-CoV-2-IgG ranged from 6.25 to 200 EIU/mL, the accuracy in-batch ranged from 81.793% to 106.985%, the precision in-batch ranged from 1. 100% to 13.000%, and the total error in-batch ranged from 2.988% to 22.679%. The accuracy between batches ranged from 90.788%to 96.893%, the precision between batches ranged from 4.870% to 6.272%, and the total error between batches ranged from 9.192% to 15.399%. The results of pseudovirus neutralizing antibody showed that the potency of different virus strain neutralizing antibodies were in the order of prototype strain>BA.2>BA.4/5>BF.7≈ BQ.1.1>BA.1 and the correlation between WP1 and WP2 was high (Pearson r=0. 931 1, P=0.002 3) which indicated that the potency distribution of neutralizing antibodies of different virus strain in Omicron convalescent plasma was basically stable. Compared with the mixed convalescent plasma sample G128 collected in June 2022, the potency of Omicron neutralizing antibodies of WP series were significantly higher, the ratio of BA.2 antibody to prototype antibody increased from 26.9% (before infection) to 82.6%-87.5% (after infection). The results of VN series before Omicron infection were < 100 EIU/mL, and the results of OP series after Omicron infection showed that the plasma collected from the beginning of December 2022 was the peak of antibody in the same month,and then dropped sharply, entering a short plateau in February-March 2023 (potency was about 40% of the peak value),and then dropped sharply again in April (potency was about 20% of the peak value). 【Conclusion】 The potency and proportion of neutralizing antibody against Omicron subtype in convalescent plasma after COVID-19 Omicron strain infection increased significantly. IgG antibody of plasma donors in different regions reached its peak in the month of infection, then continued to dropped sharply. The best collection period of plasma that can be used for human COVID-19 immunoglobulin for intravenous injection was 1 to 2 months after infection.

Analysis on the characteristics and liver function of occupational hepatotoxicants exposed population / 中国职业医学

Objective To investigate the characteristics and liver function of the population with occupational exposure to hepatotoxicants. Methods A total of 17 093 workers with occupational hepatotoxicants exposure who underwent occupational medical examination during their employment in a occupational medical examination institution of Shanghai in 2021 were selected as the research subjects by judgement sampling method. Occupational medical examination data were collected, and the prevalence of abnormal liver function and fatty liver were analyzed. The association between hepatotoxicants exposure and abnormal liver function were analyzed. Results The median and the 0th-100th percentiles of the duration of exposure to hepatotoxicants was 6.5(1.0-42.0) years. The prevalence of fatty liver was 48.4% and the incidence of abnormal liver function was 23.7%. Among the workers with fatty liver, the prevalence of abnormal liver function was higher in workers exposed to metals, metalloids and their compounds than in unexposed workers (33.9% vs 30.0%, P<0.01). The results of multivariate logistic regression analysis demonstrated that the risk of abnormal liver function increased with the number of different hepatotoxicants mixed exposures (all P<0.01), after correcting for confounding factors including gender, age, years of exposure, marital status, drinking, hypertension, fatty liver and blood sugar. Conclusion Exposure to hepatotoxicants is a risk factor for abnormal liver function. The more diverse types of hepatotoxicants an individual is exposed to, the stronger the association with this risk.

Associations between urinary paraben levels and obesity of 10-year-old children / 环境与职业医学

Background Parabens, a widely used class of preservatives, are suspected to be potential obesogens as emerging endocrine disrupting chemicals with reproductive and developmental toxicity. Objective To analyze five urinary parabens (PBs) and estimate the associations of exposure to PBs with adiposity measures in 10-year-old school-age children. Methods A total of 471 school-age children aged 10 years from the Sheyang Mini Birth Cohort were enrolled in this study. A questionnaire survey was conducted to collect socio-demographic information, physical activity, and dietary intake. Weight, height, and waist circumference of children were measured, and age- and sex-adjusted body mass index (BMI-Z score) was calculated. Spot urine samples were collected during the follow-up visits. Urinary concentrations of five PBs including methyl-paraben (MeP), ethyl-paraben (EtP), propyl-paraben (PrP), butyl-paraben (BuP), and benzyl-paraben (BzP) were detected by gas chromatography-tandem mass spectrometry (GC-MS/MS). Generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR) models were applied to estimate associations of individual/overall urinary PBs concentrations with BMI Z-score and waist circumference. Results The positive rates of selected five urinary PBs were in the range from 78.98% to 98.94%. The urinary PBs concentrations (geometric mean) were in the range of 0.31-5.43 μg·L−1. The children's BMI Z-score and waist circumference (mean ± standard deviation) were (0.56±1.40) and (67.62±10.07) cm respectively. The GLMs results showed that the urinary BzP concentration was negatively associated with waist circumference (b=−0.08, 95%CI: −0.14, −0.02; P=0.01). In sex-stratified analysis, the urinary concentration of BzP was negatively associated with BMI-Z score (b=−0.59, 95%CI: −0.88, −0.30; P<0.001) and waist circumference (b=−0.80, 95%CI: −1.23, −0.37; P<0.001) in boys, but not in girls. The BKMR results also found significant negative correlations of urinary BzP concentrations with BMI-Z score and waist circumference, which were consistent with the GLM results. Conclusion The selected 10-year-old children are extensively exposed to PBs in the study area. Furthermore, childhood PBs exposure may have potential impacts on childhood adiposity measures with sex-specific effects.

Effects of flurochloridone on apoptosis and Nrf2/HO-1 and NFκB signaling pathways in mouse testis and TM4 cells / 环境与职业医学

Background Flurochloridone (FLC) is toxic to male reproduction and can induce apoptosis of testicular tissue and supporting cells under oxidative stress. Of particular concern is whether nuclear factor-erythrocyte 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway and nuclear factor kappa B (NFκB) signaling pathway participate this process. Objective To observe apoptosis of testicular tissue and sertoli TM4 cells and alterations of Nrf2/HO-1 and NFκB signaling pathways in mice treated with FLC in vivo/in vitro. Methods (1) Animal experiment. Testis samples were harvested from male C57BL/6 mice after 28-day FLC (0, 3, 15, 75, and 375 mg·kg−1 per day) exposure via oral route. Malondialdehyde (MDA) and superoxide dismutase (SOD) in homogenate of testicular tissue were measured by colorimetry. Apoptosis of testicular tissue was evaluated by TUNEL staining. Expression and distribution of Nrf2 and NFκB were detected by immunohistochemistry. Protein expression levels of Nrf2, HO-1, NAD(P)H: quinone oxidoreductase 1 (NQO1), NFκB, inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), and phosphorylated recombinant inhibitory subunit of nuclear factor kappa-B alpha (P-IκBα) in testicular tissue homogenate were determined by Western blotting. (2) Cell experiment. TM4 cell lines were treated with 40, 80, 120, 160, and 200 μmol·L−1 FLC for 6 h, and cell viability was detected by CCK-8. After 6 h exposure to 40, 80, and 160 μmol·L−1 FLC, the apoptosis rate was detected by flow cytometry, and the protein expression levels of Nrf2, HO-1, NQO1, NFκB, IKKβ, and IκBα were detected by Western blotting. Results (1) Animal experiment. Apoptosis occurred in the interstitial and basal parts of spermatogenic tubules in male C57BL/6 mice after 28 days of oral FLC exposure. Compared with the control group, the MDA level in testicular tissue of the 375 mg·kg−1 FLC-treated group was significantly increased (P<0.05), and the SOD activity was significantly decreased (P<0.05). After 375 mg·kg−1 FLC exposure, apoptosis occurred in the interstitial and basal parts of spermatogenic tubules. The results of immunohistochemistry showed the expression of Nrf2 and NFκB in the interstitium and basal part of spermatogenic tubules of the treated groups. Compared with the control group, the protein levels of Nrf2, NQO1, P-IκBα, NFκB, and IKKβ in the 15, 75, and 375 mg·kg-1 groups were significantly increased (P<0.001), and the HO-1 protein level was significantly increased in the 375 mg·kg−1 group (P<0.001). (2) Cell experiment. Compared with the control group, the TM4 cell viabilities in the 40, 80, 120, 160, and 200 μmol·L−1 FLC-treated groups significantly decreased (P<0.01). The apoptosis rates were significantly increased (P<0.05), and the apoptosis rates increased from 5.7% in the control group to 7.4%, 9.4%, and 11.7% in the 40, 80, and 160 μmol·L−1, respectively. The Nrf2 protein level in the 40 μmol·L−1 group was significantly increased (P<0.01), while the levels significantly decreased in the 80 and 160 μmol·L−1 groups (P<0.01). The HO-1 protein levels in the 40, 80, and 160 μmol·L−1 groups were significantly increased (P<0.01). The level of NQO1 protein in the 40 μmol·L−1 group was significantly increased (P<0.01). The NFκB protein levels were significantly increased in the 80 and 160 μmol·L−1 groups (P<0.001). The IκBα protein levels were significantly decreased in all treated groups (P<0.001). The IKKβ protein had no significant change. Conclusion FLC induces testicular tissue apoptosis, and the process affects Nrf2/HO-1 signaling pathway and NFκB signaling pathway. The in vitro study confirms that FLC could induce apoptosis of TM4 cells and activate Nrf2/HO-1 and NFκB signaling pathways.

Bayesian network analysis of long-term oncologic outcomes of open, laparoscopic, and robot-assisted radical cystectomy for bladder cancer.

BACKGROUND: To understand the long-term oncologic outcomes of open radical cystectomy (ORC) versus laparoscopic radical cystectomy (LRC) versus robot-assisted radical cystectomy (RARC) for bladder cancer (BCa). Therefore, we performed the conventional meta-analysis and network meta-analysis to evaluate the long-term oncologic outcomes of ORC, LRC, and RARC for BCa. METHODS: A systematic search of PubMed, Embase, Cochrane Library, Medline, and Web of science was performed up until July 1, 2021. Long-term oncologic outcomes include the 5-year overall survival (OS) rate, the 5-year recurrence-free survival (RFS) rate, and the 5-year cancer specific-survival (CSS) rate. The Bayesian network analysis has been registered in PROSPERO (CRD42020208396). RESULTS: We found that 10 articles (including 3228 patients) were included in our Bayesian network analysis. No significant differences were found between ORC, LRC, and RARC in long-term oncologic outcomes in either direct meta-analysis or network meta-analysis. Therefore, the clinical effects of 5-year OS, RFS, and CSS of RARC, LRC, and ORC are similar. But LRC may be ranked first in 5-year OS, RFS, and CSS compared to other surgical approaches by probabilistic analysis ranking via Bayesian network analysis. CONCLUSION: We found that there were no statistical differences in the 3 surgical approaches of RAPC, LPC, and OPC for Bca in long-term oncologic outcomes by direct meta-analysis. However, Subtle differences between these surgical approaches can be concluded that LRC may be a better surgical approach than RARC or ORC in long-term oncologic outcomes by probabilistic analysis ranking via Bayesian network analysis. Moreover, we need a large sample size and more high-quality studies to improve and verify further.

Effects of paraquat on proliferation and neurogenesis of neural stem cells by promoting secretion of IL-1β by microglia / 环境与职业医学

Background Paraquat (PQ) is a widely used herbicide that exerts neurotoxicity. The effects of PQ on neural stem cells (NSCs) through microglia mediated neuroinflammation remain limitedly studied. Objective To investigate the effects of PQ on the proliferation and neurogenesis of NSCs through neuroinflammation mediated by microglia. Methods Microglial cell lines (BV2 cells) and primary NSCs were used. BV2 cells were exposed to 0, 1, 3.3, 10, 33, and 100 μmol·L−1 of PQ for 6 h followed by viability assessment. The highest PQ concentration that had no effect on cell viability was selected as the final exposure concentration (33 μmol·L−1). To exclude the direct effect of PQ on NSCs, after the BV2 cells were cultured in complete medium containing 33 μmol·L−1 PQ for 6 h, the BV2 culture medium was replaced by NSCs complete medium without PQ for 24 h. The concentration of interleukin-1β (IL-1β) in supernatant was detected by enzyme-linked immune sorbent assay. Besides, in order to detect the effects of IL-1β on NSCs proliferation and neurogenesis, NSCs isolated from hippocampus of adult mice were cultured in the supernatant obtained above and divided into four groups: control supernatant + control antibody, control supernatant + IL-1β neutralizing antibody (10 ng·mL−1), PQ supernatant + control antibody, PQ supernatant + IL-1β neutralizing antibody (10 ng·mL−1). Proportion of Ki67-positive NSCs was detected by flow cytometry (FCS) and immunofluorescence after 24 h culture, and neurogenesis was detected by FCS and immunofluorescence after 3-7 d of culture. Results The IL-1β concentration in the supernatant of BV2 cells was significantly increased after the 33 μmol·L−1 PQ exposure compared with the control group (t=3.020, P<0.05). After the NSCs were cultured with the supernatant of PQ-treated BV2 cells, the proportion of Ki67-positive NSCs (t=9.129, P<0.01) and the proportion of newborn neurons (t=4.638, P<0.01) were significantly decreased compared to the control group. After neutralizing IL-1β, the proportion of Ki67-positive NSCs (t=22.05, P<0.01) and the proportion of newborn neurons (t=11.09, P<0.01) were significantly higher than those in the un-neutralized group. The results of immunofluorescence detection also showed that after neutralizing IL-1β secreted by 33 μmol·L−1 PQ-treated BV2 cells, the number of Ki67-positive NSCs and the number of newborn neurons were significantly higher than those in the un-neutralized group. Conclusion The secretion of IL-1β by microglia is increased after PQ treatment, resulting in a decrease in the proliferation and neurogenesis of NSCs. These results suggest that neuroinflammation is involved in NSCs damage caused by PQ.

Flurochloridone-induced apoptosis via IRE1α-JNK signaling pathway in mice testicular cells and TM4 cells / 环境与职业医学

Background Flurochloridone (FLC) can induce apoptosis in Sertoli cells, but the specific mechanism remains unknown. Objective To investigate the testicular cell apoptosis in mice as well as apoptosis and activation of endoplasmic reticulum stress in TM4 cell line induced by FLC through in vivo and in vitro study designs respectively, and study the role of inosital-requiring enzyme 1α (IRE1α)-c-Jun N-terminal kinase (JNK) signaling pathway in the process of FLC-induced apoptosis in TM4 cells through intervention study design. Methods Testicular tissues were collected from male C57BL/6 mice which were treated with 3, 15, 75, and 375 mg·（kg·d）−1 FLC by oral perfusion for 28 d. Apoptosis was observed by TUNEL staining, and the levels of apoptosis-related proteins were detected by Western blotting, including B-cell lymphoma-2 (Bcl-2), Bcl-2 interacting mediator of cell death (Bim), and Bcl-2 associated X protein (Bax). In the in vitro study, TM4 cells were treated with different concentrations of FLC (40, 80, and 160 μmol·L−1) for 6 h, then apoptosis rate was detected by flow cytometry, and the levels of apoptosis-related proteins (Bcl-2, Bim, and Bax) and endoplasmic reticulum stress-related proteins [glucose regulated protein 78 (GRP78), phosphorylated-protein kinase R like endoplasmic reticulum kinase (p-PERK), activating transcription factor 6 (ATF6), phosphorylated-inosital-requiring enzyme 1α (p-IRE1α), and phosphorylated-JNK (p-JNK)] were measured by Western blotting. In the intervention study, TM4 cells were pretreated with IRE1α phosphorylation inhibitor 4μ8C and JNK phosphorylation inhibitor SP600125 for 6 h, then treated with 160 μmol·L−1 FLC for 6 h. The levels of apoptosis-related proteins and endoplasmic reticulum stress-related proteins were measured by Western blotting, and cell viability was detected by cell counting kit-8. Results After the male C57BL/6 mice orally exposed to FLC for 28 d, apoptosis occurred in the seminiferous tubule. The protein expression level of Bcl-2, apoptosis inhibitor, was decreased in the 75 and 375 mg·(kg·d)−1 groups (P<0.05), and the protein expression levels of Bim and Bax, apoptosis promoters, were increased in the 75 and 375 mg·(kg·d)−1 groups respectively (P<0.05). The percentages of apoptotic cells in the 0, 40, 80, and 160 μmol·L−1 FLC groups were 2.7%±0.2%, 4.8%±1.3%, 9.4%±0.3%, and 13.2%±0.2%, respectively, increased significantly compared with the control group (P<0.05). The protein expression level of Bcl-2 also was decreased in the 160 μmol·L−1 FLC group (P<0.05), while the levels of Bim and Bax were increased in both of the 80 and 160 μmol·L−1 groups (P<0.05). The expression levels of endoplasmic reticulum stress-related proteins (GRP78, p-PERK, ATF6, p-IRE1α, and p-JNK) were increased (P<0.05) or showed a rising trend in TM4 cells. Pre-treatment with 4μ8C (25 and 50 μmol·L−1) and SP600125 (10 and 20 μmol·L−1) significantly down-regulated the protein expression levels of GRP78, p-IRE1α, p-JNK, and Bax induced by FLC (P<0.05) or in a downward trend. Both of the inhibitors alleviated the decreased cell viability induced by FLC (P<0.05) or in alleviating fashion. Conclusion FLC could induce apoptosis in mice testis and TM4 cell apoptosis through activating endoplasmic reticulum stress and IRE1α-JNK signaling pathway.

Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.

Review on effects of heavy metals on sleep / 环境与职业医学

　　Heavy metals including lead, cadmium, manganese, and mercury are important raw materials and auxiliary materials in industrial production, but they are also seriously polluting the environment. While most of the early toxicological data on heavy metals are derived from studying occupational exposure populations, the general adult population and the infants and adolescents are now increasingly being studied for the health hazards of heavy metals. Epidemiological and laboratory studies have clearly demonstrated the neurotoxicity of heavy metals and sleeping is heavily regulated and coordinated by nervous system. Based on available epidemiological studies, the paper reviewed the effects of heavy metals on sleep status of occupational and non-occupational (general adults as well as infants and adolescents) populations. In addition, it presented the associated mechanisms in terms of sleep-wake cycle and sleep-related neurochemicals.

The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study

Currently, there are no approved specific antiviral agents for 2019 novel coronavirus disease (COVID-19). In this study, ten severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 days after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 days. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 days. Several parameters tended to improve as compared to pre-transfusion, including increased lymphocyte counts (0.65x109/L vs. 0.76x109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesionswithin 7 days. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was welltolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials. Significance StatementCOVID-19 is currently a big threat to global health. However, no specific antiviral agents are available for its treatment. In this work, we explored the feasibility of convalescent plasma (CP) transfusion to rescue severe patients. The results from 10 severe adult cases showed that one dose (200 mL) of CP was welltolerated and could significantly increase or maintain the neutralizing antibodies at a high level, leading to disappearance of viremia in 7 days. Meanwhile, clinical symptoms and paraclinical criteria rapidly improved within 3 days. Radiological examination showed varying degrees of absorption of lung lesions within 7 days. These results indicate that CP can serve as a promising rescue option for severe COVID-19 while the randomized trial is warranted.

Expression of long-chain non-coding RNA CTA-796E4.4 in bladder cancer and its effect on cell proliferation and invasion / 中国医师进修杂志

Objective:To investigate the expression of long-chain noncoding RNA (lncRNA) CTA-796E4.4 in bladder cancer tissues and cell lines, and to observe its effect on the proliferation and invasion of bladder cancer cells and to explore its possible molecular mechanism.Methods:The expression of CTA-796E4.4 in 73 bladder cancer tissues and adjacent tissues, 4 kinds of bladder cancer cell lines (UM-UC-3, BIU-87, 5637, T24) and normal bladder epithelial cells in the First People′s Hospital of Tianmen City from November 2016 to January 2019 were detected by qPCR. UM-UC-3 cells infected with recombinant lentivirus (LV-CTA-796E4.4) carrying the CTA-796E4.4 gene were taken as an experimental group, and UM-UC-3 cells infected with negative control lentivirus (LV-NC) were as a control group. The effect of over expression of CTA-796E4.4 on the expression of Forkhead box transcription factor O1 (FOXO1) mRNA was detected by qPCR. The expression of FOXO1 protein was detected by Western blotting, Thiazolyl blue (MTT) method Transwell invasion assay was respectively used to examine the effect of high expression of CTA-796E4.4 on proliferation and invasion of UM-UC-3 cells.Results:The expression level of CTA-796E4.4 in bladder cancer tissue was lower than that in para cancerous tissue (1.22 ± 0.33 vs. 4.30 ± 0.64) and the difference was statistically significant ( P < 0.01). The expression of CTA-796E4.4 in bladder cancer cells was lower than that in bladder cancer epithelial cells (0.11 ± 0.03, 0.61 ± 0.03, 0.33 ± 0.03, 0.73 ± 0.04 vs.1.01 ± 0.10) ( P < 0.01). After LV-CTA-796E4.4 infection, the expression of CTA-796E4.4 was significantly increased ( P < 0.01) and the expression of FOXO1 gene was increased ( P < 0.01). High expression of CTA-796E4.4 significantly inhibited cell proliferation and invasion of UM-UC-3 cells ( P < 0.05). Conclusions:The expression of lncRNA CTA-796E4.4 is decreased in bladder cancer and cell lines. High expression of CTA-796E4.4 inhibites the proliferation and invasion of UM-UC-3 cells. The molecular mechanism may be that up-regulation of CTA-796E4.4 can promote the expression of FOXO1.

The necessity of presetting ureteral stents before ureteroscopic lithotripsy :a Meta-analysis / 中华泌尿外科杂志

Objective To systematically evaluate the necessity of presetting double-J stent before flexible ureteroscope lithotripsy.Methods Computer retrieved clinical studies on the effect of preoperative presetting double-J-catheter on flexible ureteroscope lithotripsy in PubMed,Cochrane Library,Embase,Scopus,Wan fang,CNKI and VIP databases were reviewed.The retrieval time was from the database construction to November 2018.All of the possible combinations of the following terms were used for the search:flexible ureteroscopic,preoperative,double J stent,and calculus.Two researchers independently conducted literature screening,quality evaluation and data extraction,and completed Meta analysis by using statistical software RevMan5.3.Results Thirty-two case-control trials and 14 randomized controlled trials were screened,with a total of 17 480 patients,including 6 211 patients in the experimental group and 11 269 patients in the control group.The results of meta-analysis showed that the experimental group was superior to the control group in term of the overall postoperative stone clearance rate (OR =1.69,95％ CI 1.37-2.08,P ＜0.05).In terms of postoperative kidney stone removal rate,the experimental group was superior to the control group (OR =1.67,95％ CI 1.41-1.99,P ＜ 0.05).In terms of the removal rate of ureteral calculi after surgery,there was no significant difference between the two groups (OR =1.71,95％ CI 0.91-3.20,P =0.10).The success rate of flexible ureteroscope access sheath implantation was higher in the experimental group (OR =5.77,95％ CI 3.32-10.31,P ＜0.05).The rate of passive usage balloon dilation in the control group was higher (OR =0.23,95％ CI 0.15-0.35,P ＜ 0.05).For the incidence of intraoperative complications,the experimental group was lower (OR =0.56,95％ CI 0.38-0.84,P =0.004).For the incidence of postoperative complications,the experimental group was also lower (OR =0.64,95％ CI 0.45-0.90,P =0.01).The operation time of the control group was longer (MD =-4.95,95 ％ CI -8.90--1.01,P =0.01).Conclusions Presetting double-J-catheter can improve the stone removal rate after flexible ureteroscope lithotripsy for the treatment of kidney stone,improve the success rate of flexible ureteroscope access sheath implantation,reduce the utilization rate of ureteral balloon dilator,reduce the incidence of intraoperative and postoperative complications,and shorten the operation time.

Clinical practice of 177Lu-PSMA-RLT in the treatment of prostate cancer / 中华核医学与分子影像杂志

Prostate cancer is one of the malignant tumors with high incidence. Although most patients with prostate cancer respond well to standard treatment, they often have a poor prognosis once they develop hormone resistance. Radionuclide targeted therapy is an important method to treat malignant tumors after surgery and chemo-radiotherapy. New radioligand therapy (RLT), represented by 177Lu-prostate specific membrane antigen (PSMA)-RLT, effectively solves the problem of poor efficacy in advanced hormone-resistant prostate cancer, and has been widely recognized in the world. In this paper, the clinical practice of 177Lu-PSMA-RLT in the treatment of prostate cancer and its common adverse reactions are described in order to better understand and master its methods and lay the foundation for better clinical application and follow-up research.

Effect of long-chain noncoding RNA NEAT1 on the proliferation and invasion of renal cell carcinoma / 中国医师杂志

Objective To observe the expression of long non-coding RNA (LncRNA-NEAT1) in renal cell carcinoma and cell lines,and to explore its influence on the malignant biological behavior of renal cell carcinoma and its possible molecular mechanism.Methods The expression of NEAT1 was detected by quantitative polymerase chain reaction (qPCR) in l0 cases of renal cell carcinoma and paracancerous tissues,and in 4 types of renal cell carcinoma cells and normal renal tubular epithelial cells.ACHN cells infected with negative control lentivirus (LV-NC) were used as control group,and ACHN cells infected with recombinant lentivirus carrying NEAT1 gene (LV-NEAT1) were used as experimental group.Bioinformatics predicts targeted miRNA and downstream genes of NEAT1.The effect of overexpression of NEAT1 on the mRNA expression of miR-342-3p and cell adhesion molecule 1 (CADM1) was detected by qPCR.The protein expression of CADM1 was detected by Western blot.The proliferation and invasion of ACHN cells were detected by methyl thiazolyl tetrazolium (MTT) method and Transwell invasion assay.Results The expression level of NEAT1 in renal cell carcinoma was lower than that in paracancerous tissue (P ＜ 0.01).The expression of NEAT1 in renal carcinoma cell lines was lower than that in renal tubular epithelial cells (P ＜0.01).After LV-NEAT1 infection,the expression of NEAT1 and CADM1 gene were significantly increased (P ＜0.01),while the expression of miR-342-3p decreased (P ＜0.01).Overexpression of NEAT1 significantly inhibited cell proliferation and invasion of ACHN cells (P ＜ 0.05).Conclusions LncRNA NEAT1 was down-regulated in renal cell carcinoma and cell lines.Overexpression of NEAT1 inhibited the proliferation and invasion of ACHN cells.The molecular mechanism may be that NEAT1 up-regulates the expression of CADM1 gene through complementary binding to miR-342-3p.

Investigation on the application of GBZ/T 229.2-2010——classification of occupational hazards at workplaces Part 2: occupational exposure to chemicals / 中华劳动卫生职业病杂志

Objective@#To investigate the application and effectiveness evaluation of the standard of GBZ/T 229.2-2010 in practice, and to explore the applicability, aiming to provide technical evidence for the re-vision of GBZ/T 229.2-2010.@*Methods@#There were 2 questionnaire surveys carried out in the study, including general survey and specific survey. Databases were established and data were input with Excel 2010 and Epi-data version 3.1 software. SPSS version 19.0 software was used for data cleaning and statistical analysis.@*Results@#In total, the general survey received 100 questionnaires, with 59 from occupational health technical ser-vice organizations held by government, and 11 from colleges and universities. The leading three jobs using GBZ/T 229.2-2010 were the occupational hazards evaluation for constructive project (65.0%), lecturing/train-ing (50.0%), occupational hazards monitoring (43.0%), respectively. In the results of feasibility, scores of the fourth part "classification" , the fifth part "the principles of classification management" , annex A "the correct use instructions" were 3.4, 3.3, 3.5 respectively. In total, the specific survey received 27 questionnaires, with 18 from the employers and 9 from occupational health technical service organizations. The awareness rate of GBZ/T 229.2-2010 among occupational health professionals was 72.2%. In the results of feasibility, scores of the level of chemical hazards, occupational exposure ratio, physical labor intensity level, classification of expo-sure to industrial toxicants, principles of classification management, annex A "the correct use instructions" were 3.2, 3.7, 4.3, 4.1, 3.2, 3.2, respectively@*Conclusions@#The results indicates that each part of GBZ/T 229.2-2010 is feasible and practical. But there are still some problems, such as classification of different kinds of chemicals at workplace, and the interaction of occupational exposure to chemicals and other hazards at work-place, etc. We suggest that in the revision of GBZ/T 229.2-2010, the action level of hazards should be clear.

Pathologic subtyping of primary lymphoma of breast and prognostic analysis / 中华病理学杂志

Objective@#To investigate the pathological types and prognostic factors of primary lymphoma of breast (PLB).@*Methods@#The clinical pathological data of 115 cases of PLB during October 2006 to October 2016 were retrospectively analyzed, and the basic clinical and pathological data, pathology types and the immunohistochemical slides by EliVision two-step method for staining were summarized.@*Results@#Almost all the patients were women (113/115), and the median age was 52 years old (range: 27 to 81 years old). The main symptom was painless progressive mass in breast. Ten cases (8.7%) showed B symptoms. The masses were mainly confined to the unilateral breast (80.9%, 93/115), of which 22 cases showed axillary lymph nodes enlargement in the same side. The average diameter of masses was 3.0 cm (range from 0.5 to 9.0 cm). There is no differences between the sides (left or right). Pathologically, 106 cases (92.2%) were mature non-Hodgkin′s B-cell lymphomas, of which there were mainly diffuse large B cell lymphoma (DLBCL, 64.3%) and mucosa associated lymphoid tissue (MALT) extranodal marginal lymphoma (17.4%). Five cases (4.4%) were mature T/NK cell lymphomas, including extranodal nasal NK/T cell lymphoma (1.7%), peripheral T-cell lymphoma non-specific type (0.9%), subcutaneous panniculitis-like T cells lymphoma (0.9%) and undivided (0.9%). Four cases were lymphoblastic lymphoma. According to Ann Arbor staging criteria, 93 cases were stage ⅠE (6 cases were stage ⅠEB), 22 cases were stage ⅡE (4 cases were stage ⅡEB). Ninety-two cases were followed 1 to 122 months (median: 36 months). The five-year overall survival rate was 85.3%, and 13 patients dead. B symptom was one of the factors that affect the prognosis (P<0.05), but the pathological type has no relationship with the prognosis (P>0.05).@*Conclusions@#PLB is relatively rare, the main clinical manifestation is painless mass, which is difficult to distinguish with breast carcinoma. The most common type is DLBCL, followed by MALT lymphoma, while T cell lymphoma is rarely seen. PLB is early stage tumor with good prognosis, while patients with B symptom turn out to suffer worse prognosis.

Mucosa-associated lymphoid tissue lymphoma in children and adolescents: a clinicopathologic study of 5 cases / 中华病理学杂志

Objective@#To investigate the pathological features and clinical manifestations of mucosa-associated lymphoid tissue (MALT) lymphoma in children and adolescents.@*Methods@#Five cases of MALT lymphoma in children were investigated by morphology and immunophenotyping along with clinical follow-up.@*Results@#Five cases of MALT lymphoma occurred in the antrum, orbit, parotid gland and nasopharynx. All patients had no B symptoms and only one patient showed a local mass with ulcer. One case presented with cervical lymph node enlargement, and 4 cases showed no evidence of lymphadenopathy.All cases had pathological features similar to those of adult MALT lymphoma, with proliferation of monocytoid B cells orcentralcyte-like tumor cells, with plasma cell differentiation and lymphoid epithelial lesions.No specific immunophenotypic marker was found. Clonal Ig gene rearrangement was detected in two cases.One patient was treated with rituximab treatment, 1 patient was given anti-Helicobacter pylori therapy, and 2 patients had no additional treatment.The follow-up data showed that 4 patients survived without tumor recurrence.@*Conclusions@#Similar to adult patients, MALT lymphoma in children and adolescents has similar pathological features with indolent clinical course and good prognosis. It is important to note that misdiagnosis and incorrect diagnosis mightoccur because of the young age of the patients.