Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.

Objective: To analyze the distribution characteristics of immunoglobulin A (IgA) concentration in Nanning Zhuang blood donors by measuring the concentration of plasma IgA. Methods: Enzyme-linked immunosorbent assay (ELISA) was performed to measure the absorbance of 2 000 plasma samples from Zhuang blood donors. The IgA concentration in samples was calculated using the ELISA Calc regression/fitting technology program. Results: The standard curve demonstrated that ELISA detection of plasma IgA concentration exhibited good precision. The frequency of IgA deficiency was 0/2 000. No statistically significant difference in the distribution of IgA concentration was observed between males and females (P>0.05). The distribution of IgA concentration varied significantly across age groups: younger individuals (18-39 years old) had lower plasma IgA levels (mg/dL) compared to older individuals (40-56 years old): 5-89.99 mg/dL group, 8.80% (176/2 000) vs 17.20% (344/2 000); 90-450 mg/dL group,20.65% (413/2 000) vs 51.20% (1 024/2 000); >450 mg/dL group, 0.45%, (9/2 000) vs 1.70% (34/2 000), P<0.05. No significant difference in IgA concentration was found among different ABO blood types in Zhuang blood donors (P>0.05). Spearman correlation analysis revealed a positive correlation between age and IgA concentration (R =0.114, P<0.05). Conclusion: No individuals with IgA deficiency were screened out among the Zhuang blood donors in Nanning area, and plasma IgA levels progressively increase with age.

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Objective To establish the genetic typing detection technique of matrix-assisted laser de-sorption ionization-time or flight mass spectrometry(MALDI-TOF MS),and to apply it to investigate the polymorphism of the human platelet antigen(HPA)-29-35w low-frequency gene in blood donor population from Guangxi area.Methods The RS number of 7 target gene mutation sites in dbSNP and 21 primers were designed by using Assay Design Suite(ADS)of MassARRAY platform online primer design tool.Seven over-expression vectors inserting into HPA-29-35bb mutant sequence were constructed.Twenty-nine blood donors were randomly selected among the blood donors team in Guangxi area.The samples and vectors conducted the iPLEX Pro multiple genotyping analysis and mass spectrometric detection.Meanwhile,the above samples were sequenced and the sequencing results conducted the comparison validation with the mass spectrometric detec-tion results,then the MALDI-TOF MS genotyping detection technology was established.Then adopting this technology conducted the platelet antigen HPA-29-35W genotyping detection and polymorphism analysis in the samples from 588 blood donors in Guangxi area.Results The MALDI-TOF MS HPA genotyping detec-tion results were consistent with the sequencing results.The HPA-29-35w genotyping results showed that theHPA-29-35w genotype of 588 blood donors in Guangxi area was aa homozygote.Conclusion The genotype detection method of MALDI-TOF MS for HPA-29-35w is successfully established and applied to the screening of HPA-29-35w gene among the blood donor population in Guangxi area.

Chinese medicine therapy for removing gallstones is one of the methods for the treatment of cholelithiasis.In the view of Professor Liu Fengbin,attacking of external pathogens,improper diet and emotional disorders contribute to the main causes of cholelithiasis,and the pathogenesis of cholelithiasis is due to qi stagnation of both liver and gallbladder,and internal obstruction of damp-heat.The occurrence of cholelithiasis is closely related to deficiency of spleen and stomach,and is correlated with the pathological factors of turbid phlegm and blood stasis.For the Chinese medicine treatment of cholelithiasis,Professor Liu follows the principle of"treatment in accordance with three categories of etiological factors"(i.e,seasons,environment and body constitution).He advocates the integration of traditional Chinese medicine and western medicine,and is good at utilizing Lingnan herbs and distinctive herbs that can dissolve stones and remove stones.The treatment for cholelithiasis is mainly through the therapies of soothing liver and alleviating depression,clearing heat and removing dampness,and normalizing gallbladder function to remove stones,and is also supplemented by the therapies of invigorating spleen and replenishing qi,regulating qi to resolve phlegm,and activiting qi movement and blood circulation.Modified Da Chaihu Decoction plus Sijin Decoction is often used as a basic formula for treating cholelithiasis,which is mainly composed of Desmodii Styracifolii Herba,Galli Gigerii Endothelium Corneum,Bupleuri Radix,Curcumae Radix,Scutellariae Radix,Aucklandiae Radix,Aurantii Fructus Immaturus stir-fried with bran,Paeoniae Radix Rubra,Linderae Radix,and Rhei Radix et Rhizoma.

Objective To investigate the influence of herbal compatibility on the chemical composition of Banxia Houpo Decoction(BHD)using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS)coupled with multivariate statistical analysis,and to evaluate the neuroprotective effects of key differential components against neuroinflammation and neuronal injury using cellular models.Methods(1)UPLC-MS analysis of chemical constituents in co-decoction and separated decoction(individual herbs decocted separately then combined)of Banxia Houpo Decoction,followed by orthogonal partial least squares-discriminant analysis(OPLS-DA)to identify differential components before and after herbal compatibility(2)BV2 microglia were stimulated with lipopolysaccharide(LPS)to establish a neuroinflammation model.Cell viability was assessed using the Cell Counting Kit 8(CCK-8)assay.Nitric oxide(NO)levels were measured by the Griess method,while TNF-α and IL-1β concentrations were quantified via enzyme-linked immunosorbent assay(ELISA).(3)SH-SY5Y neuronal cells were co-cultured with conditioned medium from LPS-stimulated BV2 cells(LPS-CM)to model neuronal injury.Cell viability was evaluated using the CCK-8 assay.Results UPLC-MS/OPLS-DA identified 11 differential components between compatibility methods,with honokiol and magnolol showing significant post-compatibility increases.In the neuroinflammation model,LPS stimulation elevated NO,TNF-α and IL-1 β levels in BV2 cells,which were suppressed by 5,10 μg/mL honokiol or magnolol.In the neuronal injury model,LPS-CM induced SH-SY5Y apoptosis,while 5,10 μg/mL honokiol or magnolol attenuated this damage.Conclusion Herbal compatibility significantly enhances honokiol and magnolol content in BHD.These components inhibit microglial inflammatory responses and neuronal apoptosis,suggesting their role as primary active constituents mediating BHD's neuroprotective effects.

Objective To retrospectively analyze the blood use of transfusion-dependent thalassemia(TDT)patients in 9 designated transfusion medical institutions from 2018 to 2023 in Nanning,and to evaluate the effect of"three designated"blood transfusion mode(hereby means TDT patients undergoing blood transfusion in designated transfusion medical institu-tions regularly)and"collection-based-supply"blood management mode on blood security of TDT patients.Methods The"three designated"blood transfusion mode was implemented to ensure that TDT patients registered in the local household registration(referred to as the"register")obtain the rights and interests of outpatient transfusion and blood security of des-ignated medical institutions.The"collection-based-supply"blood management mode was implemented to assess the blood needs of"register"TDT patients and meet their needs to the maximum extent according to the blood inventory(collection).Results From 2018 to 2023,the total blood supply of"register"TDT patients was 10.37%of the total red blood supply of all medical institutions(138 509.5 U/1 335 788.0 U),with the highest proportion of type O blood as 46.34%(64 181.0 U/138 509.5 U)and the lowest proportion of type AB blood as 3.85%(5 331.0 U/138 509.5 U).In 2018,9 transfusion medical institutions were designated for TDT patients.There were a total of 766 TDT patients in the register,with the per ca-pita annual blood transfusion volume increased from20.28 U(15 531.0 U/766 patients)in2018 to36.01 U(27 586.0 U/766 patients)in 2023,maintaining a positive growth every year(30.26%,4.94%,11.71%,8.61%,4.94%and 7.10%).Conclusion The"three designated"blood transfusion mode and the"collection-based-supply"blood management mode can effectively guarantee the blood supply of TDT patients.

Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

International Agency for Research on Cancer (IARC) classifies nickel compounds as Class Ⅰ carcinogens. International Labour Organization (ILO) also lists nickel compounds as carcinogenic factors of occupational cancer. At present, China is revising the Classification and Catalogue of Occupational Diseases, and cancer caused by nickel compounds may also be included in the statutory occupational diseases. The Diagnostic and Exposure Standards for Occupational Diseases published by ILO in 2022 discussed the pathogenic characteristics, occupational exposure, main health effects, diagnostic criteria and key preventive measures of nickel compounds in detail. This article mainly introduces its contents, in order to provid a basis for the formulation of relevant standards in China.