OBJECTIVE: To analyze the phenotype and genotype of a neonate with Osteo-oto-hepato-enteric syndrome (O2HE) and review the literature. METHODS: A female neonate diagnosed with O2HE syndrome on December 13, 2024 at the First Affiliated Hospital of Zhengzhou University was selected as the study subject, and her clinical characteristics were analyzed, and pathogenic variants were explored by whole exome sequencing (WES). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-KY-1038). RESULTS: The proband, a female infant, was delivered by Cesarean section at 36⁺¹ weeks of gestation. Five days after birth, she had developed severe diarrhea, mild cholestasis, sensorineural hearing loss, and growth retardation. WES revealed that she has harbored novel compound heterozygous variants c.512delA (p.Lys171Serfs*64) and c.698C>A (p.Thr233Asn) of the UNC45A gene, which were inherited from her mother and father, respectively. A total of 8 English papers were retrieved, which involved 16 patients from 14 families. Combined with our case, the 17 patients included 13 (76.5%) females and 4 (23.5%) males. Four patients (23.5%) had consanguineous parents. One case was excluded from further genetic analysis due to co-morbidity with other genetic variants. The primary clinical features included diarrhea (87.5%), cholestasis (81.3%), sensorineural hearing loss (31.3%), bone fragility (37.5%), and developmental delay (50.0%). Bi-allelic compound heterozygous mutations were identified in 12 patients (75.0%), and homozygous variants in 4 (25.0%). These included missense, nonsense, frameshift and deletional variants. The c.710T>C (p.Leu237Pro) variant was identified for 5 times, 3 of which were in homozygote forms. CONCLUSION O2HE syndrome should be suspected in cases with diarrhea, cholestasis, and hearing abnormalities during early postnatal period. Genetic testing facilitate early identification, genetic diagnosis and treatment.
Humans ; Female ; Infant, Newborn ; Male ; Mutation ; Hearing Loss, Sensorineural/genetics* ; Diarrhea, Infantile/genetics* ; Exome Sequencing ; Phenotype ; Fetal Growth Retardation ; Hair Diseases ; Facies

This paper systematically elaborates on the key points of diagnosis and differential diagnosis of salivary gland tumors characterized by a substantial amount of extracellular mucus as a main or prominent feature, and clarifies the core differential features. The term "mucus-rich" specifically denotes that mucus is a major component of the tumor, rather than a focal or minor one. This phenomenon is associated with distinct histogenetic mechanisms: it may result from specific genetic mutations (e.g., AKT1 E17K in mucinous adenocarcinoma) that drive ductal epithelial differentiation into mucus-secreting cells, or from myoepithelial cells secreting glycosaminoglycans that form a myxoid stroma. Salivary gland tumors with abundant extracellular mucus include mucinous cystadenoma, sialadenoma papilliferum-like intraductal papillary tumors, mucinous myoepithelioma, pleomorphic adenoma with mucin-rich stroma, mucinous adenocarcinoma, low-grade mucoepidermoid carcinoma, mucin-rich salivary duct carcinoma and intestinal-type adenocarcinoma. The diagnosis of these tumors is complicated by the dual nature of extracellular mucus: while it is a defining feature of some entities, it can also obscure key diagnostic architectural features in others, leading to histological overlap and inconspicuous diagnostic areas. Given the frequent histological morphological overlap among these tumors, immunohistochemical findings and molecular characteristics have emerged as crucial differential diagnostic criteria. Core differential diagnostic points include the following: histologically, there must be meticulous identification of typical structures obscured by mucin (such as squamoid cells in mucoepidermoid carcinoma and apocrine features in salivary duct carcinoma); in immunohistochemical staining, CK20 is useful for distinguishing intestinal-type adenocarcinoma (positive) from mucinous adenocarcinoma (negative), while androgen receptor aids in differentiating salivary duct carcinoma (positive) from mucoepidermoid carcinoma (negative); and molecular testing plays a critical role in definitive diagnosis (e.g., the AKT1 E17K mutation for mucinous adenocarcinoma, MAML2 rearrangement for mucoepidermoid carcinoma, and MEF2C::SS18 fusion for microsecretory adenocarcinoma). This paper systematically summarizes the core pathological features and differential diagnostic points of mucin-rich salivary gland tumors, aiming to provide a practical reference for clinical pathological diagnosis.

To investigate the in vitro inhibitory mechanism of Nymphaea candida total flavonoids(NCTF)against Staphylococcus aureus(S.aureus)and its safety in mice,this study first deter-mined the antibacterial effect of NCTF on the clinically isolated strain S.aureus-C1.Subsequently,the inhibitory mechanism of NCTF on S.aureus-C1 was explored by measuring its effects on bac-terial growth curves,microstructure,intracellular AKP and LDH levels,and biofilm formation.Safety evaluation included determination of LD50 and MDT in mice,as well as analysis of serum biochemical parameters,organ indices,and histopathological observations.Results showed that NCTF effectively inhibited S.aureus-C1 proliferation,with an inhibition zone diameter of(18.98±0.67)mm and a MIC of 6.25 g/L.A concentration of 2×MIC nearly completely suppressed bacte-rial growth.Scanning electron microscopy revealed structural damage to bacterial cells,including collapse and shrinkage.AKP and LDH assays indicated significantly increased AKP activity(P＜0.05)and decreased intracellular LDH activity(P＜0.05)in the supernatant of drug-treated groups,demonstrating NCTF-induced disruption of cell walls and membranes leading to leakage of AKP and LDH.Crystal violet staining of biofilms showed significant inhibition rates of(43.77±9.16)％and(61.71±9.82)％at 2 × MIC and 4 × MIC concentrations,respectively(P＜0.05).Safe-ty assessments indicated low toxicity of NCTF in mice,with transient effects that returned to nor-mal levels within a short period.These findings demonstrate that NCTF exhibits potent antibacte-rial activity against S.aureus-C1 by damaging bacterial cell structures,increasing cell wall/mem-brane permeability,reducing biofilm formation,and displaying low toxicity.This study provides scientific evidence for clinical drug screening against bovine mastitis and the development of Nym-phaea candida resources.

OBJECTIVE To investigate the distribution and drug resistance of the pathogens isolated from sterile body fluids in a hospital so as to provide reference for clinical treatment of the infections.METHODS The sterile body fluids specimens that were cultured positive for pathogens were retrospectively collected from a three-A hos-pital of Jiangxi Province between 2016 and 2023.The distribution and drug resistance of the isolated pathogens were observed.RESULTS Totally 16,658 strains of pathogens were isolated from the sterile body fluid speci-mens in 2016-2023,among which gram-negative bacteria accounted for 51.74％.The species of bacteria that ranked the top 5 places were as follows:Escherichia coli,Klebsiella pneumoniae,Staphylococcus epidermidis,Staphylococcus hominis,and Staphylococcus aureus.The isolation rates of methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus were 28.32％and 74.94％,respectively;the strains maintained high sensitivity to linezolid and vancomycin,with the drug resistance rates no more than 2.50％.The drug resistance rates of Enterococcus faecium and Enterococcus faecalis to linezolid and vancomycin were always less than 4.20％.Among the species of Enterobacter,the drug resistance rates of the E.coli strains to meropenem declined from 17.65％to 5.94％;conversely,the drug resistance rate of the K.pneumoniae strains to carbapenems reached high up to 54.36％,showing an upward trend on the whole.Among the non-fermenting gram-negative bacteria,the drug resistance rate of the A.baumannii strains to carbapenems remained high(about 80.00％);while the drug resistance rates of the P.aeruginosa strains to meropenem dropped from 60.71％down to 24.32％.CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the ster-ile body fluids in the hospital between 2016 and 2023.Although some major species of drug-resistant pathogens are effectively under control,the pathogens isolated from the sterile body fluid specimens maintain varying degree of drug resistance to various types of antibiotics.

Diabetic cardiomyopathy(DCM)is a serious complication of diabetes mellitus(DM).Recent studies have reported that the NOD-like receptor protein 3(NLRP3)inflammasome activation-mediated pyroptosis aggravates the formation and development of DCM.This review summarizes the mechanism of action of NLRP3 inflammasome in the development of DCM,and focus on the potential effects of targeted inhibition of NLRP3 inflammasome activation in the treatment of DCM.

Diabetic cardiomyopathy(DCM)is a serious complication of diabetes mellitus(DM).Recent studies have reported that the NOD-like receptor protein 3(NLRP3)inflammasome activation-mediated pyroptosis aggravates the formation and development of DCM.This review summarizes the mechanism of action of NLRP3 inflammasome in the development of DCM,and focus on the potential effects of targeted inhibition of NLRP3 inflammasome activation in the treatment of DCM.

Ferroptosis is a non-apoptotic programmed cell death driven by iron ion-mediated lipid peroxidation,which is closely related to the occurrence and development of various tumors.In recent years,many studies have shown that non-coding RNA(ncRNA)can affect tumor drug resistance by regulating the ferroptosis pathway.This article summarizes the molecular mechanisms of ncRNAs regulating sorafenib resistance in hepatocellular carcinoma(HCC)through ferroptosis,with a focus on the regulatory roles of different ncRNA subtypes such as microRNA(miRNA),long noncoding RNA(lncRNA),and circular RNA(circRNA).The article not only contributes to a deeper analysis of the key molecular mechanisms by which ncRNA mediate sorafenib resistance in HCC through ferroptosis pathways,but also provides a theoretical basis for exploring novel diagnostic biomarkers and therapeutic targets for HCC in the future.

Metabolic dysfunction-associated fatty liver disease(MAFLD)is becoming an leading causes of hepatic fibrosis worldwide,resulting in MAFLD-related liver fibrosis.Emerging evidences have indicated that the activation of the NOD-like receptor family Pyrin domain containing 3(NLRP3)inflammasome is a critical contributor to the development of MAFLD-related liver fibrosis.This article reviews the mechanism by which NLRP3 inflammasome activation promotes the development of MAFLD-related liver fibrosis,and focuses on the pharmacological mechanism of drugs targeting NLRP3 inflammasome to treat MAFLD-related liver fibrosis.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

AIM:Flow cytometry was used to evaluate the effects of short-term storage conditions(fresh,frozen at-80℃for 7 d,and stored at 4℃for 7 d)on the median fluorescence intensity(MFI)of antibodies and the percentage of immune cell subsets in mouse peripheral blood mononuclear cells(PBMCs)and splenocytes.METHODS:The PBMC and splenocyte suspensions from six male Kunming mice were collected and analyzed under three different processing con-ditions to compare differences in the antibody MFI and percentages of monocyte subsets(Ly-6clow/Ly-6cmedium/Ly-6chigh),macrophages(M1/M2),and dendritic cells.RESULTS:Both tissue and antibody specificity were demonstrated by changes in the antibody MFI values.Following storage at-80℃,the MFIs of certain antibodies(such as CD45 and F4/80 in PBMCs,and CD115,Ly-6c,F4/80,CD80 and MHC-II in the spleen)were similar to those of the fresh groups,where-as after storage at 4℃,the MFIs of other antibodies(such as 7-AAD,CD115,Ly-6c and MHC-II in PBMCs,and CD11b,CD206 and CD11c in the spleen)were closer to those of the fresh groups.The MFI of most of the examined anti-bodies varied significantly following storage.Both storage conditions significantly reduced the viability of PBMCs and sple-nocytes.In PBMCs stored at 4℃,the percentages of total monocytes,Ly-6cmedium/Ly-6chigh monocytes,total macrophages,and dendritic cells were similar to those in the fresh group.Compared with the fresh group,both storage groups presented significantly lower percentages of M1 macrophages and dendritic cells(P<0.05).There were no statistically significant differences in the percentages of total monocytes,Ly-6cmedium monocytes,Ly-6chigh monocytes,total macrophages,M1 and M2 macrophages,or dendritic cells in the spleen among the three groups(P>0.05).The percentage of Ly-6clow monocytes did not differ substantially(P>0.05)between the fresh and-80℃frozen groups but was significantly lower in the 4℃storage group than in the fresh group(P<0.05).CONCLUSION:The storage conditions of the samples had a substantial effect on the flow cytometry results(antibody MFI and cell subset percentages)of the PBMCs and splenic cells,with tissue specificity.If the percentage of immune cell subgroups(particularly monocytes/macrophages/dendritic cells)in PBMCs is highly important,storage at 4℃for 7 d is preferable.If the MFI values of specific antibodies(such as CD45 and F4/80)are important,freezing at-80℃may be more appropriate.If the MFI values of most antibodies or the percentages of criti-cal subgroups(such as total monocytes/Ly-6chigh/total macrophages/dendritic cells)in splenic cells need to be close to those of fresh samples,4 ℃ storage for 7 d is more effective.Freezing at-80℃is preferable if the MFI values of particular anti-bodies(such as CD115 and Ly-6c)need to be determined.