Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

【Objective】 To investigate the distribution of ABO and RhD blood groups among voluntary blood donors in Guangzhou, in order to ensure clinical blood safety and better serve blood donors. 【Methods】 Routine ABO and RhD blood group screening tests were carried out among voluntary blood donors from January 2021 to December 2022. The composition ratio of ABO blood group was statistically analyzed. The samples with discrepancy between forward and reverse blood grouping and negative RhD blood group samples were further verified by serological test to analyze the ABO subtypes and the reasons for missed detection. 【Results】 A total of 749 123 blood samples were screened from January 2021 to December 2022, and 513 291 samples were collected after excluding repeat blood donors, with the ABO blood groups as 208 126(40.55%) of O type, 138 859(27.05%) of A type, 130 987(25.52%) of B type and 35 319(6.88%) of AB type. The screening results showed discrepancy between forward and reverse blood grouping in 506 samples, of which 58 were with weak/non-erythrocyte reaction, 16 with erythrocyte reaction, 215 with weak/non-serum reaction, and 217 with serum reaction. Further serological test indicated that 44 samples were ABO subtypes, among which 13 were subtype A, 26 subtype B, 5 subtype AB and 3 B (A) and 14 Bombay-like blood group. The blood group with the highest missed detection rate in repeat blood donors were A3/B3 subtype (68.42%). A total of 128 unexpected antibody positive samples were detected among 513 291 samples A total of 2 277 samples were screened negative for RhD blood type, of which 2 188 were confirmed to be Rh negative (2 188/513 291, 0.43%), 89 were D variants (89/513 291, 0.02%, ) and 30 were detected with unexpected antibodies (30/2 188, 1.37%). 【Conclusion】 The ABO blood group distribution of blood donors in Guangzhou is O>A>B>AB, and the proportion of RhD negative population is 0.43%, slightly highter than 0.3%-0.4% of Han population nationwide. The ABO blood group subtype is dominated by B subtype. The detection rate and missed detection rate of A3/B3 subtypes in routine blood group tests are the highest.

[Objective] To analyze the influence of the cycle length of hepatitis B surface antigen (HBsAg) double reagent positive samples collected from voluntary blood donors in Guangzhou on the detection results. [Methods] A total of 127 044 blood samples from voluntary blood donors at Guangzhou Blood Center from August 10 to December 9, 2023 were selected. Two ELISA reagents were used for HBsAg detection, and samples with HBsAg double reagent positive and S/CO values<10 were tested continuously for 7 days to observe the changes in their S/CO values. [Results] A total of 505 HBsAg double reagent positive samples were detected, of which 52 had S/CO values less than 10. After 7 consecutive days of uninterrupted testing, the S/CO values of Wantai (median 5 decreased to 3) and Xinchuang (median 5 decreased to 3) showed an overall downward trend, and the HBsAg missed detection rate showed an upward trend (from 0 on the first day to 1/10 000 on the seventh day). A total of 13 cases had negative double reagent test results within the 7-day testing cycle. [Conclusion] With the extension of the detection cycle, the S/CO value of HBsAg detection shows a downward trend, and the missed detection rate of HBsAg shows an upward trend. Samples used for HBsAg detection should be tested promptly after sampling to improve the quality of blood testing.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Objective To analyze the characteristics of work-related musculoskeletal disorders (WMSDs) among sonographers in Guangdong Province, and to explore the disease pattern of the cases. Methods A total of 512 sonographers from 31 hospitals in Guangdong Province were selected as the research subjects using stratified cluster sampling method. The prevalence of WMSDs in the past year was investigated using the Musculoskeletal Disorders Questionnaire, and the characteristics of WMSDs were analyzed. Latent class analysis was used to identify the disease pattern of WMSDs. Results The overall prevalence of WMSDs was 94.3%. The top five affected body parts were right shoulder, neck, right hand/wrist, lower back and right forearm/elbow, with the prevalence of 80.3%, 75.4%, 61.1%, 55.5% and 45.3%, respectively. The prevalence of WMSDs was higher on the right side for the shoulder, hand/wrist, forearm/elbow, hip/leg and knee compared with the left side (80.3% vs 31.3%, 61.1% vs 13.9%, 45.3% vs 10.0%, 17.4% vs 8.6%, 13.1% vs 8.4%, all P<0.05). The prevalence of WMSDs increased with work years, as well the prevalence of WMSDs in the top five affected body parts among the sonographers (all P<0.05). However, there were no statistical differences in prevalence of WMSDs between general hospitals and maternal and child health hospitals, tertiary hospitals and non-tertiary hospitals, Pearl River Delta hospitals and non-Pearl River Delta hospitals; there was also no statistical difference between different genders and age groups of the sonographers (all P>0.05). The best-fit latent disease pattern for sonographers WMSDs comprised three categories： symptom of neck-right shoulder, symptom of neck-lower back-right shoulder-right elbow-right hand/wrist, and symptom of multi-parts above the knees, with the latent probabilities of 0.438, 0.427 and 0.135, respectively. Conclusion The prevalence of WMSDs in sonographers is extremely high, with a dose-effect relationship with work years. The most common affected parts are neck, lower back and right shoulder, right hand/wrist, and right forearm/elbow. The prevalence of WMSDs in the right side of limb was higher than that in the left. WMSDs primarily occur in multiple parts simultaneously. The most common symptoms occur in the neck-right shoulder and neck-lower back-right shoulder-right elbow-right hand/wrist.

【Objective】 To explore the correlation between serological screening of human T-lymphotropic virus antibodies (anti HTLV) and Western blot(WB) confirmatory tests among blood donors, so as to explore the infection status of HTLV Ⅰ/Ⅱ in Guangzhou. 【Methods】 The anti HTLV Ⅰ/Ⅱ enzyme-linked immunosorbent assay(ELISA) kit was used to screen voluntary blood donors from Guangzhou Blood Center from July 2016 to August 2022. WB was used to confirm 395 reactive blood samples by ELISA. The correlation between the S/CO values of anti HTLV Ⅰ/Ⅱ ELISA reagents and the confirmatory test was analyzed using ROC curves. 【Results】 The results showed that 25 out of 395 initially screened reactive blood donor samples were confirmed as HTLV positive by WB, while 16 were uncertain. ROC curve analysis showed a correlation between the S/CO values by ELISA and the confirmatory test results: the S/CO value at the highest Youden index was 3.789, which was the optimal threshold. The S/CO value had a certain correlation with the predicted positive rate of confirmatory results (P<0.05): the larger the S/CO value, the higher the predicted positive value. The overall prevalence of HTLV in Guangzhou is relatively low. 【Conclusion】 The prevalence of HTLV among blood donors in Guangzhou is low.Since the false positive rate of HTLV Ⅰ/Ⅱ antibody by ELISA serological screening is high, the confirmatory testing is particularly important.

【Objective】 To assess the trend of hepatitis B virus (HBV) prevalence and associated risk factors among voluntary blood donors in Guangzhou area from 2011 to 2020, and to explore the impact of hepatitis B vaccination in neonates on the risk of HBV infection. 【Methods】 Blood samples of 2 624 434 voluntary blood donors from 2011 to 2020 in Guangzhou were tested by HBV surface antigen (HBsAg) enzyme-linked immunosorbent assay (ELISA) reagents twice and nucleic acid test (NAT) reagent once. Samples reactive to ELISA twice, or ELISA once + NAT were considered as HBV infection. The gender, age, ethnicity and region of HBV infected blood donors were collected, and the incidence of HBV infection in blood donors born before and after 1992 (when HBV vaccination was conducted in neonates) was compared. The trend and risk factors of HBV infection in blood donors in Guangzhou from 2011 to 2020 were analyzed. 【Results】 An overall HBV prevalence of 0.75% was found in voluntary blood donors in Guangzhou area from 2010 to 2020, showing an overall downward trend(P<0.05). HBV prevalence was lower in blood donors born after 1992 (0.49 %, 4 825/98 5362) than prior to 1992 (P<0.05). HBV prevalence in male blood donors (0.89%, 15 049/1 695 062) was significantly higher than that in female blood donors (P<0.05). HBV prevalence in blood donors aged 18~25(0.52%, 6 337/1 219 282)was lower than that in other age groups (P<0.05). HBV prevalence was similar in donors resident in Guangdong and other provinces(P>0.05), but both were significantly higher than that in Hong Kong, Macao, Taiwan and foreign countries (P<0.05). HBV prevalence in Han nationality donors was significantly higher than the ethnic minority donors (P<0.05). Gender, age, ethnicity and birth vaccination are the main risk factors for HBV infection among blood donors. 【Conclusion】 The overall HBV prevalence among voluntary blood donors in Guangzhou area from 2011 to 2020 has shown a decreasing trend, and differences have been found in gender, age, region, ethnicity and birth vaccination, which is helpful to formulate targeted recruitment strategies, thus reducing the risk of transfusion transmitted HBV.

Objective To investigate the effect of Shuganning injection (SGN) in alleviating drug-induced cholestasis and the possible mechanisms involved. Methods The liver of Sprague-Dawley rats was decellularized to prepare collagen scaffolds, and then the scaffolds were recellularized with human HepG2 cells to obtain the tissue-engineered liver (normal control group). The tissue-engineered liver was perfused with 10 μmol/L chlorpromazine (CPZ) and bile salt mixture to establish a model of drug-induced cholestasis (CPZ group), and the model was further treated with Shuganning injection (10 3 -fold dilution) as the injury protection group (SGN+CPZ group). The markers for hepatocellular injury [alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP)] and the antioxidant and oxidative stress markers [glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS)] were measured for all groups, and the normal control group, the CPZ group, and the SGN+CPZ group were compared in terms of the mRNA and protein expression levels of the enzymes associated with liver bile salt metabolism and the enzymes associated with hepatic cholestasis. HE staining was performed to observe liver pathology. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the CPZ group, the SGN+CPZ group had significant reductions in the markers for hepatocellular injury ALT, AST, LDH, and ALP (all P < 0.000 1), significant increases in the oxidative stress markers GSH and SOD ( P < 0.000 1 and P < 0.001), and significant reductions in the markers MDA and ROS ( P < 0.000 1 and P < 0.001). Compared with the CPZ group, the SGN+CPZ group had significant reductions in the mRNA expression levels of cholesterol 7α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CPY8B1) in hepatocytes (all P < 0.001) and significant increases in the mRNA expression levels of farnesoid X receptor (FXR), small heterodimeric partner (SHP), bile salt export pump (BSEP), and multidrug resistance-associated protein 2 (MRP2) ( P < 0.000 1, P < 0.01, P < 0.000 1, and P < 0.000 1). HE staining showed that compared with the CPZ group, the SGN+CPZ group had a significant reduction in hepatocyte injury and a significant increase in the number of cells. Conclusion Shuganning injection can alleviate drug-induced cholestatic liver injury caused by chlorpromazine, and it exerts a protective effect by activating FXR in hepatocytes and increasing the expression of SHP to regulate bile salt balance. It also inhibits CYP7A1 and CYP8B1 to reduce the synthesis of hydrophobic bile acids and upregulates the expression of BSEP and MRP2 to promote the excretion of bile salts.

Diamond-Blackfan anemia(DBA)is a rare hereditary anemia.About 90% of them have symptoms in infancy, and about 50% are complicated with congenital malformations.Genetic abnormalities were found in 70% to 80% of DBA cases, mainly autosomal dominant inheritance, and a few were recessive or X-linked inheritance.The main gene mutations of DBA are ribosomal protein gene mutations and deletions.More than 20 mutation genes related to DBA have been found in the ribosomal protein(RP)gene encoding ribosome, of which RPS19 gene mutation is the most common.In addition, there are TSR2 genes related to ribosome function and non-RP genes related to DBA like phenotype, such as GATA1, EPO and ADA2 genes.These genes play a key role in the differentiation and proliferation of erythroid cells.Molecular diagnosis is an important criterion to diagnose and distinguish classical DBA from non-classical DBA.This review summarizes the latest research progress in the genetics, gene mutation and molecular diagnosis of DBA.

Objective:To investigate the therapeutic effect of cardiac rehabilitation exercise on ventricular remodeling in patients with acute myocardial infarction undergoing percutaneous coronary intervention.Methods:A total of 100 patients with acute myocardial infarction undergoing percutaneous coronary intervention who received treatment in Wenzhou Central Hospital from June 2018 to June 2019 were included in this study. They were randomly divided into a rehabilitation group and a conventional treatment group ( n = 50/group). Patients in the conventional treatment group underwent conventional postoperative rehabilitation education while those in the rehabilitation group received targeted cardiac rehabilitation exercise. After surgery, all patients were followed up for 12 months. Real time three-dimensional echocardiography was used to evaluate ventricular remodeling (left ventricular ejection fraction, left ventricular end-diastolic volume , left ventricular end-systolic volume, left ventricular remodeling index) and ventricular synchrony (Tmsv-16dif, Tmsv-16sd, Tmsv16-dif%, Tmsv16-sd%) before and 3, 6 and 12 months after surgery. In addition, serum levels of ventricular remodeling indexes (fibroblast growth factor 23, PICP and PIIINP) were measured. The incidence of cardiovascular end-point events within 12 months was calculated. Results:At 3, 6 and 12 months after surgery, left ventricular ejection fraction was (51.81 ± 5.43)%, (55.88 ± 5.46)%, (55.63 ± 5.57)% in the rehabilitation group, which was significantly higher than (47.16 ± 5.38)%, (52.31 ± 5.44)%, (51.84 ± 5.59)% respectively in the conventional treatment group ( t = 4.302, 3.275, 3.396, all P < 0.05). At 3, 6 and 12 months after surgery, left ventricular end-diastolic volume was (124.65 ± 15.56) mL, (98.54 ± 14.54) mL, (99.82 ± 13.18) mL, respectively in the rehabilitation group, which was lower than (132.64 ± 16.58) mL, (112.55 ± 15.61) mL and (114.84 ± 17.35) mL, respectively in the conventional treatment group ( t = 2.485, 4.644, 4.874, all P < 0.05). At 6 and 12 months after surgery, left ventricular end-systolic volume was (52.26 ± 5.48) mL and (52.15 ± 5.32) mL respectively in the rehabilitation group, which was significantly lower than (57.92 ± 5.46) mL and (58.51 ± 5.72) mL in the conventional treatment group ( t = 5.174, 5.757, both P < 0.05). At 6 and 12 months after surgery, left ventricular remodeling index was (1.75 ± 0.42) g/mL and (1.74 ± 0.35) g/mL respectively in the rehabilitation group, which was significantly higher than (1.52 ± 0.37) g/mL and (1.50 ± 0.32) g/mL, respectively in the conventional treatment group ( t = 2.906, 3.579, both P < 0.05). At 3, 6 and 12 months after surgery, Tmsv-16dif ( t = 2.753, 4.283, 4.088, all P < 0.05), Tmsv-16sd ( t = 5.134, 4.326, 4.670, all P < 0.05), Tmsv-16dif% ( t = 7.714, 8.587, 7.800, all P < 0.05) and Tmsv16-sd% ( t = 9.004, 14.061, 10.305, all P < 0.05) respectively in the rehabilitation group, were significantly lower than those in the conventional treatment group. At 3, 6 and 12 months after surgery, fibroblast growth factor 23 ( t = 6.303, 5.053, 4.619, all P < 0.05). PICP ( t = 3.772, 2.798, 3.788, all P < 0.05) and PIIINP ( t = 3.110, 5.912, 4.294, all P < 0.05) in the rehabilitation group were significantly lower than those in the conventional treatment group. Within 12 months, the total incidence of cardiovascular end-point events in the rehabilitation group [12.00% (6/50)] was significantly lower than that in the conventional treatment [32.00% (16/50)] ( χ2 = 5.828, P < 0.05). Conclusion:Cardiac rehabilitation exercise can improve ventricular remodeling and synchrony in patients with acute myocardial infarction undergoing percutaneous coronary intervention and reduce the incidence of cardiovascular end-point events.