Objective: To investigate the indoor fine particulate matter (PM 2.5 ) pollution and its influencing factors in children s bedrooms using solid fuel, so as to provide evidence for effective strategy to reduce PM 2.5 pollution. Methods: From December 2019 to November 2020, 198 households (108 in the north, 90 in the south) from two pilots in the north(Jiamusi in Heilongjiang Province) and south of China (Mianyang in Sichuan Province) were selected, and status of solid fuels using were obtained through home visits, dynamic changes in PM 2.5 concentrations in children s bedrooms were monitored by using real time online instruments, and the influencing factors of PM 2.5 pollution were analyzed by using a mixed effects model. Results: During the monitoring period, the daily PM 2.5 concentrations in the northern and southern pilot were 78.33 (40.50, 154.80) and 38.54(26.20, 58.46) μg/m 3, respectively, exceeding standard rates of 44.57% and 33.22%. During the heating period, the daily PM 2.5 concentrations in the northern and southern pilot were 212.50(133.60,244.10) and 104.42(73.97, 134.90) μg/m 3, respectively, with over standard rates of 96.75% and 86.96%. The mixed effects model analysis results showed that children s bedroom PM 2.5 concentrations were associated with solid fuel usage duration, window opening time, room layout (shared entrance door between kitchen and bedroom), indoor smoking, indoor humidity, and solid fuel use in the bedroom ( β =0.19, -0.05, 1.20, 0.43, 0.02, 0.35, all P <0.05). Conclusion Solid fuel combustion significantly comtributes to PM 2.5 pollution in children s bedrooms, with more pronounced impacts observed in northern China compared to southern regions.

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Background Multiple studies have shown a close relationship between changes in gut microbiota composition and obesity, and research results are influenced by factors such as race and geographical location, but there are few studies on children. Objective To analyze the diversity of gut microbiota related to obesity in a population of 2-6 years old, observe the distribution characteristics and species differences of gut microbiota between obese/overweight and normal weight groups, and explore the association betweenobese/overweight and gut microbiota diversity. Methods Fecal samples were collected from 74 children aged 2-6 years in Shanghai, including 18 obese/overweight individuals, 6 males and 12 females (male to female ratio of 1∶2), and 56 normal weight individuals, 18 males and 38 females (male to female ratio is nearly 1∶2). The 16S rDNA was extracted from bacteria in fecal samples, followed by PCR amplification, cDNA construction, and high-throughput sequencing. Naive Bayes algorithm was used to perform taxonomic analysis (phylum, class, order, family, genus, species) and community diversity analysis (Sobs index, Shannon index, Shannoneven index, Coverage index, PD index, and principal co-ordinates analysis) on representative sequences and abundance of amplicon sequence variants (ASV). Wilcoxon rank sum test, P-value multiple test correction, and analysis of similarities were used to test differences between the two groups to obtain information on the distribution characteristics and species differences of intestinal microbiota in children. Results Seventy-four fecal samples were sequenced, and the sequencing results were subjected to quality control and filtering. A total of 4905306 optimized sequences were obtained, resulting in 1860 ASVs. The diversity data analysis of ASVs generated 889 species annotation results at 8 taxonomic levels. The alpha diversity analysis showed that the richness (Sobs index), diversity (Shannon index), evenness (Shannoneven index), and phylogenetic diversity (PD index) of fecal community of the obese/overweight children were increased compared to those of the normal weight children, but there were no statistical differences between the two groups (P>0.05). The beta diversity analysis showed that there was little difference in the composition of microbial species between the two groups, and no significant clustering separation was observed. The results of species composition analysis at phylum, order, family, and genus levels of 74 samples showed a consistent core microbiota structure in the two groups of gut microbiota, but there were differences in microbiota composition. The differences in microbial community composition between the two groups were manifested at the taxonomic levels of order, family, and genus, among which phylum Firmicutes, order Erysipelotrichales, family Erysipelatocyclostridiaceae, genus Erysipelotrichaceae_ UCG-003 and genus Catenibacterium were significantly enriched in the obese/overweight group and contributed significantly to the phenotypic difference of obese/overweight [linear discriminant analysis (LDA)=3.72, P<0.01; LDA=3.29, P<0.05). Phylum Proteobacteria, order Enterobacterales, family Enterobacteriaceae, genus unclassified was significantly enriched in the normal weight group and contributed significantly to the phenotypic difference of normal body weight (LDA=3.93, P<0.05). Conclusion The richness and diversity of gut microbiota in obese/overweight children aged 2-6 years in Shanghai are increased, but there is no difference compared to normal weight children. There is a difference in the composition of gut microbiota between the obese/overweight group and the normal weight group.

AIM To explore the effects of Zishui Qinggan Decoction on the mouse model of depression induced by chronic restraint stress(CRS)via ERK/GSK3β/CREB/BDNF signaling pathway.METHODS Except for those of the blank group,the mice of other groups were induced into depression models by CRS,and divided into the model group,the fluoxetine hydrochloride group(10 mg/kg)and the low,medium and high dose Zishui Qinggan Decoction groups(8.835,17.670 and 35.340 g/kg)for the corresponding drug intervention and simultanous CRS treatment.The mice had their sugar water preference experiment and behavior experiment on the 7th and 14th day after administration;the observation of the hippocampal morphological changes by HE staining,the detection of the superoxide dismutase(SOD)activity and malondialdehyde(MDA)level in serum by kits,the detection of levels of serum 5-hydroxytryptamine(5-HT),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)by ELISA,the detection of the hippocampal mRNA expressions of BDNF,TNF-α and IL-1β by RT-qPCR method,and the detection of the hippocampal protein expressions of ERK1/2,p-ERK1/2,GSK3β,p-GSK3β,CREB and BDNF by Western blot method 14 days after administration.RESULTS Compared with the model group,after 14 days of administration,both fluoxetine hydrochloride group and medium-dose Zishui Qinggan Decoction group displayed increased preference rate of sugar water(P<0.01),shortened immobility time of tail suspension and forced swimming(P<0.01),improved hippocampal damage of nerve cells,decreased levels of serum MDA,TNF-α and IL-1β(P<0.05,P<0.01),increased SOD activity and 5-HT level(P<0.05,P<0.01),decreased hippocampal mRNA expressions of TNF-α and IL-1β(P<0.01),and decreased expressions of BDNF mRNA and p-ERK1/2,p-GSK3β,CREB and BDNF proteins(P<0.05,P<0.01).CONCLUSION Zishui Qinggan Decoction can improve the depression-like behaviors in mice exposed to CRS,and its mechanism may be related to the regulation of hippocampal ERK/GSK3β/CREB/BDNF signaling pathway.

AIM To study the secondary metabolites from the endophytic fungi Candida sp.of Berberis atrocarpa Schneid.METHODS The ethyl acetate fraction and petroleum ether fraction from the secondary metabolites of Candida sp.fermentation extract were separated and purified by silica gel,Sephadex LH-20 and preparative liquid chromatography,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as 1-phenyl-1,2-ethanediol(1),4-hydroxyphenethyl alcohol(2),4-hydroxybenzoic acid(3),4-hydroxyphenylacetic acid(4),3-hydroxyphenylacetic acid(5),3-methylsulfinyl propionic acid(6),phenylacetic acid(7),(S)-N-nitroso-1-amino-p-hydroxy phenylethanol(8),2-phenylacetamide(9),p-hydroxybenzaldehyde(10),ethyl 2-(4-hydroxyphenyl)acetate(11),dibutyl phthalate(12),5,5'-dimethoxybiphenyl-2,2'-diol(13),3-indolealdehyde(14),N-acetyl-L-phenylalanine(15),9-hydroxy-10E,12Z-octadecadienoic acid(16),9-hydroxy-10E,12E-octadecadienoic acid(17),(6E)-5-methylene-6-tetradecenoic acid(18).CONCLUSION Compounds 1,3-8 and 10-18 are isolated from Candida sp for the first time.

Objective To investigate the effect of rutin on pyroptosis of nucleus pulposus cells in rats with intervertebral disc degeneration and its mechanism at cellular level.Methods Rat interdisc nucleus pulposus cells were randomly divided into control group,model group[interleukin-1β(IL-1β)induction],experiment-L group(25 μmol·L-1 rutin+10 ng·mL-1 IL-1β),experiment-M group(50 μmol·L-1 rutin+10ng·mL-1IL-1β),experiment-H group(100 μmol·L-1 rutin+10 ng·mL-1 IL-1 β),experiment-H+SRT1720 agonist group[100 μmol·L-1 rutin+10 ng·mL-1 IL-1 β+1 μmol·L-1 silent information regulator 1(SIRT1)agonist SRT1720].Real-time quantitative polymerase chain reaction(RT-qPCR)assay and Western blot assay were used to detect the expression of related genes and proteins;cell count kit-8(CCK-8)assay and enzyme-linked immunosorbent assay were used to detect the expression of cell viability and inflammatory factors,respectively.Results The cell activities of control group,model group,experimental-H group and experimental-H+SIRT1 agonist group were(100.00±3.56)％,(47.30±2.58)％,(57.33±3.41)％,(66.15±4.85)％,(76.78±2.83)％and(85.84±4.84)％;SIRT1 mRNA expression levels were 1.00±0.12,0.25±0.02,0.39±0.04,0.52±0.03,0.67±0.08 and 0.83±0.09;tumor necrosis factor-α(TNF-α)expression level were(15.03±1.21),(126.50±8.84),(112.60±12.29),(83.71±6.85),(53.88±3.43)and(28.19±4.02)pg·mL-1;the relative expression levels of PTEN-induced putative kinase 1(PINK1)protein were 0.30±0.03,0.26±0.04,0.39±0.04,0.65±0.06,0.89±0.12 and 1.28±0.08;the relative expression levels of gasdermin D-N(GSDMD-N)were 0.38±0.02,1.20±0.08,0.89±0.06,0.69±0.07,0.53±0.05 and 0.40±0.03,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically different(all P＜0.05).There were statistically significant differences in the above indexes between the experimental-H+SIRT1 agonist group and the experimental-H group(all P＜0.05).Conclusion Rutin can induce mitochondrial autophagy by activating SIRT1,inhibit pyroptosis of nucleus pulposus cells and alleviate intervertebral disc degeneration in rats.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Aim To establish the fingerprint of raw bupleurum and vinegar bupleurum,investigate the difference in their anti-liver fibrosis effects,and ex-plore the relationship between the chemical composition of raw bupleurum and vinegar bupleurum and their an-ti-liver fibrosis efficacy.Methods The fingerprints of 10 batches of raw bupleuri and 10 batches of bupleuri were established by UPLC method.The liver fibrosis cell model in vitro was established by TGF-β induced LX-2 hepatic stellate cells.The liver fibrosis cell mod-el was analyzed with collagen type Ⅰ(col1a1)and α-smoothmuscleactin.The expression of α-SMA protein was used as the pharmacodynamic index.MetaboAna-lyst5.0 was used to screen the difference markers af-fecting the quality of raw bupledges and vinegar bu-pledges with VIP value＞1 as the criterion.Orthogo-nal partial least squares discriminant analysis(OPLS-DA)was used to screen the main components of raw bupleurum and vinegar bupleurum against liver fibro-sis.Results There were 18 peaks in the UPLC fin-gerprints of raw bupleurum and vinegar bupleurum,and the analysis results showed that there were nine main differences between raw bupleurum and vinegar bupleurum,among which peaks 9,7 and 6 could be considered as bupleurin d,bupleurin a and bupleurin f.The results of spectral effect relationship showed that the main components of bupleurum anti-liver fibrosis were peaks 11,12,14,15 and 18.Conclusions The established fingerprint method of raw bupleurum and vinegar bupleurum is simple and feasible,and the important components of anti-liver fibrosis activity are screened through the spectrum effect relationship,which provides a basis for clarifying the material basis of anti-liver fibrosis effect of raw bupleurum and vine-gar bupleurum.