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 establish an active monitoring model for adverse reactions/events of sodium-glucose cotransporter 2 inhibitor (SGLT2i) for application and promotion in medical institutions.Methods:The subjects were type 2 diabetes patients who were discharged from the First Affiliated Hospital of Guangdong Pharmaceutical University (our hospital) from March 1, 2021 to October 1, 2022 and treated with SGLT2i. The patients were divided into 2 parts and assigned to the pre-trial phase and clinical application validation phase, respectively. SGLT2i-related adverse reactions/events from domestic and foreign databases and drug labels were retrieved, and triggering items were developed preliminarily. After soliciting opinions from experts in our hospital, referring to relevant medical orders, disease course records, and laboratory indicator reference values, the triggering items were modified, and a questionnaire survey was conducted using the Delphi method. According to expert opinions, the items were sorted, analyzed, discussed, and modified to form preliminary triggering items. A monitoring model was established based on the Chinese hospital drug surveillance system, the triggering items were improved during the pre-trial phase, and validated during the clinical application phase.Results:A total of 218 and 858 patients were obtained in the pre-trial phase and clinical application validation phase, respectively. Based on literature and drug labels, 44 triggering items were preliminarily formed. A total of 16 survey questionnaires from experts were collected. After being modified based on expert opinions, and further improved during the pre-trial phase, 24 triggering items were determined finally, including 8 laboratory indicators (A), 4 rescue agents (B), 11 clinical symptoms (C), and 1 intervention measure (D). The number of positive cases monitored by the model during the pre-trial phase and clinical application validation phase was 56 and 189, respectively. The actual number of positive cases under manual review was 12 and 57, respectively. The positive predictive value (PPV) of the triggering items in the pre-trial phase and clinical application phase were 25.0% (18/72) and 30.9% (77/249), respectively, with adverse reaction/event detection rates of 5.5% (12/218) and 6.6% (57/858), sensitivity of 92.3% (12/13) and 100% (57/57), and specificity of 78.5% (161/205) and 83.5% (669/801). Among the 12 positive cases in the pre-trial phase and 57 positive cases in the clinical application validation phase, the association evaluation was probable and possible (4, 8 cases and 16, 41 cases, respectively). The severity of adverse reactions/events was mainly grade 2 (11 cases and 55 cases, respectively). The main adverse reactions/events of SGLT2i were hypoglycemia, urinary tract infections, rashes, etc. Pancreatitis, weight loss, etc., which were not stated in the drug labels, were evaluated as probable.Conclusion:Through pre-trial and internal clinical validation phase, the adverse reaction/event active monitoring model established for SGLT2i in this study has high sensitivity and specificity, and can be applied practically in medical institutions.

Objective:To establish an active monitoring model for adverse reactions/events of sodium-glucose cotransporter 2 inhibitor (SGLT2i) for application and promotion in medical institutions.Methods:The subjects were type 2 diabetes patients who were discharged from the First Affiliated Hospital of Guangdong Pharmaceutical University (our hospital) from March 1, 2021 to October 1, 2022 and treated with SGLT2i. The patients were divided into 2 parts and assigned to the pre-trial phase and clinical application validation phase, respectively. SGLT2i-related adverse reactions/events from domestic and foreign databases and drug labels were retrieved, and triggering items were developed preliminarily. After soliciting opinions from experts in our hospital, referring to relevant medical orders, disease course records, and laboratory indicator reference values, the triggering items were modified, and a questionnaire survey was conducted using the Delphi method. According to expert opinions, the items were sorted, analyzed, discussed, and modified to form preliminary triggering items. A monitoring model was established based on the Chinese hospital drug surveillance system, the triggering items were improved during the pre-trial phase, and validated during the clinical application phase.Results:A total of 218 and 858 patients were obtained in the pre-trial phase and clinical application validation phase, respectively. Based on literature and drug labels, 44 triggering items were preliminarily formed. A total of 16 survey questionnaires from experts were collected. After being modified based on expert opinions, and further improved during the pre-trial phase, 24 triggering items were determined finally, including 8 laboratory indicators (A), 4 rescue agents (B), 11 clinical symptoms (C), and 1 intervention measure (D). The number of positive cases monitored by the model during the pre-trial phase and clinical application validation phase was 56 and 189, respectively. The actual number of positive cases under manual review was 12 and 57, respectively. The positive predictive value (PPV) of the triggering items in the pre-trial phase and clinical application phase were 25.0% (18/72) and 30.9% (77/249), respectively, with adverse reaction/event detection rates of 5.5% (12/218) and 6.6% (57/858), sensitivity of 92.3% (12/13) and 100% (57/57), and specificity of 78.5% (161/205) and 83.5% (669/801). Among the 12 positive cases in the pre-trial phase and 57 positive cases in the clinical application validation phase, the association evaluation was probable and possible (4, 8 cases and 16, 41 cases, respectively). The severity of adverse reactions/events was mainly grade 2 (11 cases and 55 cases, respectively). The main adverse reactions/events of SGLT2i were hypoglycemia, urinary tract infections, rashes, etc. Pancreatitis, weight loss, etc., which were not stated in the drug labels, were evaluated as probable.Conclusion:Through pre-trial and internal clinical validation phase, the adverse reaction/event active monitoring model established for SGLT2i in this study has high sensitivity and specificity, and can be applied practically in medical institutions.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation

Objective: To explore clustering and risk factors of Staphylococcus aureus (S. aureus) carriage among kindergarten children in Liuzhou. Methods: Two sided nasal swabs were collected from 1 702 children in Liuzhou from April to June 2018. Parents of all the children were investigated by questionnaires. The random effect Logistic regression was used to analyze the clustering and risk factors of S. aureus carriage. Results: The carriage rate of S. aureus among kindergarten children was 16.3%. The randomeffect Logistic regression model indicated that the class-level random effect of S. aureus carriage among children was statistically significant(Z=2.12, P<0.01). Children aged 6 to 7 years (OR=2.18, 95%CI=1.45-3.27) and 5 years (OR=1.65, 95%CI=1.08-2.50) had higher carriage rates of S. aureus than those aged 3-4 years. The history of antibiotic using (OR=1.45, 95%CI=1.05-2.01) and skin and soft tissue infections (OR=1.36, 95%CI=1.04-1.79) in the previous year were risk factors of S. aureus carriage among children. Conclusion The class level clustering of S. aureus carriage is observed in healthy children. Age, history of antibiotic usage and history of skin and soft tissue infections are associated with risk of S. aureus carriage among preschool children.

This commentary on the paper " Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study" published recently on the British Medrcal Journal (BMJ), has been focused on the analysis of the study design and the advantages/disadvantages of large-scale design. Besides discussing the main findings of the study, it is pointed out that the negative relationship between the traits should be interpreted carefully. Finally, we introduce the study design of Mendelian randomization ( MR) and randomized controlled trial (RCT), the similarities and differences between them are compared. We believe that more and more MR studies based on large-scale genome wide association study (GWAS) data will be carried out in the next few years.

Objective To identify clinical and dosimetric parameters from dose-volume histogram(DVH) relating with incidence of severe acute radiation-induced esophagitis(RE)in patients with non-small cell lung can-cer(NSCLC)underwent tomotherapy with concurrent or sequential chemotherapy. Methods Records about clini-cal information and treatment plan parameters from DVH of 62 NSCLC patients treated with tomotherapy were pro-spectively collected to assess the correlation to severe acute RE from January 2012 to December 2016. Results There were 24.2％patients developed grade 3 RE,grade 4 or 5 in 0％patients. Multivariate analysis indicated that concurrent chemotherapy,esophagus median dose and esophagus V25 and V55 were the influencing factors of RE. The incidence of low frequencies RE was correlated with sequential chemotherapy ,esophagus median dose < 49 Gy,esophagus V25 < 64％ ,V55 < 33％ and V60 < 15％. Conclusions For NSCLC patients treated with tomo-therapy and chemotherapy,the occurrence of acute RE was similar to that of other techniques. It is recommended to balance such parameters for optimizing treatment planning.

Objective To survey the basic situation of trainees, the career awareness, the requirement for training, the problems in training, and the selection to the training institutions for the health management specialist trainees. Method Using the cluster sampling method, the trainees from two health management specialist training institutions in Hunan Province were randomly selected from Oct. 2012 to Jun. 2014, a total of 543 trainees were recruited from tertiary health management specialist trainees of 12 periods training a questionnaire survey was conducted. Result Totally 474 valid questionnaires were received, the effective rate was 87.3%. The trainees were mainly from college or undergraduate settings (366, 77.2%), medical professionals (430, 90.7%). The main purpose of the training was to improve their knowledge and technique. Students' demands in the theory content for health management training mainly included the health monitoring (396, 83.5%), health education and health promotion (384, 81.0%), health risk assessment and risk management (382, 80.6%), health intervention plan formulation, implementation and evaluation (360, 75.9%). Demand for practical skills was mainly for health monitoring (426, 89.9%), health risk assessment (424, 89.5%), health interventions (410, 86.5%), health plan formulation, implementation and evaluation (402, 84.8%), health management in the application of specific people (398, 84.0%), etc. At the same time, most of the students considered that for teaching arrangement equal attention to theory and practice should be paid (320, 67.5%). Conclusion Health management specialist training is still in its infancy in China;establishment and improvement of the relevant policies about health management system and forming a complete standard set of health management specialist training system are imminent.

Objective To investigate the changes in cellular immune function and biochemical indicators of conventional submarine crew both before and after prolonged deployment at sea.Methods Sixtytwo submariners were recruited as the subjects of our study.Detections were made on T lymphocyte subpopulation and NK cell (CD3 + , CD4 + , CD8 + , CD4 +/CD8 + and NK cells) , heptorenal function as well as 13 biochemical indicators [blood glucose (Glu), aspartate amninotransferase (AST), alanine aminotransferase (ALT), AST/ALT, UREA, creatinine (CREA), potassium (K), sodium (Na) and chlorine (Cl), calcium (Ca), magnesium (Mg), phosphorus (P) and iron (Fe)].Results As compared with those before prolonged deployment at sea, CD3 + levels in the T lymphocyte subpopulation after prolonged deployment at sea (67.02％ ± 7.30％ and 68.91％ ± 8.15％ respectively) , CD4 + levels(33.59％ ± 5.61％ and 36.87％ ± 3.65 ％ respectively) , and CD4 +/CD8 + levels (1.22 ± 0.45, 1.46 ± 0.52 respectively) , were all significantly increased (P ＜-0.05).However, CD8 + levels were obviously decreased(27.32％ ± 8.21％ ,25.25％ ± 4.38％) (P ＜ 0.05).Blood glucose levels were obviously increased [(3.68 ± 0.85) mmol/L and (4.38 ± 1.15) mmol/L respectively] (P ＜ 0.05).Ca levels were also elevated [(2.48 ± 0.11) mmol/L and (2.54 ± 0.12) mmol/L respectively] (P ＜ 0.05).Na levels were respectively [(141.08 ± 5.75) mmol/L,(138.08 ± 2.86)mmol/L] , C1 levels were obviously decreased, which were respectively [(103.12 ± 3.09)mmol/L and(98.89 ±4.28)mmol/L] (P ＜0.01), and Fe levels were also obviously decreased, which were [(23.14 ± 6.75) μmol/L and (21.54 ± 7.34) μmol/L] respectively (P ＜ 0.05).Though biochemical indicators of heptorenal function were elevated to various extents, no statistical differences could be noticed (P ＞ 0.05).Conclusions The immune response of the conventional submariners during this prolonged deployment at sea was enhanced, the blood glucose and Ca levels were elevated, but Fe, Na and Cl levels were decreased, indicating that nutritional components should be adjusted in future submarine deployments at sea,and attention should be paid to the changes in blood glucose, so as to ensure the mental health of the submariners.

Objective To investigate the changes in cellular immune function and biochemical indicators of conventional submarine crew both before and after prolonged deployment at sea.Methods Sixtytwo submariners were recruited as the subjects of our study.Detections were made on T lymphocyte subpopulation and NK cell (CD3 + , CD4 + , CD8 + , CD4 +/CD8 + and NK cells) , heptorenal function as well as 13 biochemical indicators [blood glucose (Glu), aspartate amninotransferase (AST), alanine aminotransferase (ALT), AST/ALT, UREA, creatinine (CREA), potassium (K), sodium (Na) and chlorine (Cl), calcium (Ca), magnesium (Mg), phosphorus (P) and iron (Fe)].Results As compared with those before prolonged deployment at sea, CD3 + levels in the T lymphocyte subpopulation after prolonged deployment at sea (67.02％ ± 7.30％ and 68.91％ ± 8.15％ respectively) , CD4 + levels(33.59％ ± 5.61％ and 36.87％ ± 3.65 ％ respectively) , and CD4 +/CD8 + levels (1.22 ± 0.45, 1.46 ± 0.52 respectively) , were all significantly increased (P ＜-0.05).However, CD8 + levels were obviously decreased(27.32％ ± 8.21％ ,25.25％ ± 4.38％) (P ＜ 0.05).Blood glucose levels were obviously increased [(3.68 ± 0.85) mmol/L and (4.38 ± 1.15) mmol/L respectively] (P ＜ 0.05).Ca levels were also elevated [(2.48 ± 0.11) mmol/L and (2.54 ± 0.12) mmol/L respectively] (P ＜ 0.05).Na levels were respectively [(141.08 ± 5.75) mmol/L,(138.08 ± 2.86)mmol/L] , C1 levels were obviously decreased, which were respectively [(103.12 ± 3.09)mmol/L and(98.89 ±4.28)mmol/L] (P ＜0.01), and Fe levels were also obviously decreased, which were [(23.14 ± 6.75) μmol/L and (21.54 ± 7.34) μmol/L] respectively (P ＜ 0.05).Though biochemical indicators of heptorenal function were elevated to various extents, no statistical differences could be noticed (P ＞ 0.05).Conclusions The immune response of the conventional submariners during this prolonged deployment at sea was enhanced, the blood glucose and Ca levels were elevated, but Fe, Na and Cl levels were decreased, indicating that nutritional components should be adjusted in future submarine deployments at sea,and attention should be paid to the changes in blood glucose, so as to ensure the mental health of the submariners.