OBJECTIVES: To investigate the molecular mechanism by which He's Yangchao Formula improves ovarian function in premature ovarian insufficiency (POI) mice through intestinal flora modulation. METHODS: Forty female ICR mice (aged 6-8 weeks) were intraperitoneally injected with cyclophosphamide (150 mg/kg) to establish a POI model, while 10 untreated mice served as the blank control. Successfully modeled mice were randomly divided into four groups (n=10/group): low-dose He's Yangchao Formula (6 g crude herb/kg), high-dose He's Yangchao Formula (25 g crude herb/kg), positive control (estradiol), and model control (distilled water). Treatments were admin-istered daily by gavage for 6 weeks. Vaginal exfoliated cells were stained with Wright-Giemsa solution to monitor estrous cycles. Serum estradiol and follicle-stimulating hormone (FSH) levels were measured by ELISA. Ovarian FSH receptor (FSHR) expression was assessed by immunohistochemistry. Glycolysis-related proteins pyruvate kinase M2 (PKM2) and glucose transporter 4 (GLUT4) were analyzed by Western blotting and immuno-fluorescence. Fecal samples from blank control, model control, and high-dose groups underwent metagenomic sequencing to evaluate intestinal microbiota diversity and com-position. RESULTS: He's Yangchao Formula restored estrous cyclicity, increased serum estradiol (P<0.05), decreased serum FSH (P<0.05), and upregulated FSHR expression in granulosa cells (P<0.05). Metagenomic analysis revealed significant structural differences in intestinal flora among blank control, model control, and high-dose groups (P<0.01). The high-dose group showed reduced abundance of conditional pathogens (e.g., Alistipes, Prevotella, Odoribacter, Blautia, Rikenella) compared to the model control (P<0.05). Functional enrichment analysis indicated involvement of glycolysis-related pathways. Concordantly, PKM2 and GLUT4 expression was downregulated in the model control but upregulated in He's Yangchao Formula groups (P<0.05). CONCLUSIONS He's Yangchao Formula ameliorates POI in mice by remodeling intestinal flora structure, enhancing glycolytic activity, improving ovarian sex hormone secretion, increasing granulosa cell FSHR expression, and restoring estrous cyclicity.

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*

OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

Objective:To investigate the effect of Chinese medicine He's Yangchao recipe on premature ovarian insufficiency(POI)and its relationship with mitochondrial function of ovarian granulose cells in an animal model.Methods:Thirty-six female C57BL/6J mice were randomly divided into blank control group,model group,low-,medium-and high-dose He's Yangchao recipe treatment group and coenzyme Q10(Q10)treatment group(positive control).The POI model was induced by a single intraperitoneal injection of cyclophosphamide(90 mg/kg).The animals were sacrificed after 21 days.Primary granulose cells were obtained from POI mice and treated with He's Yangchao recipe,ERβ inhibitor PHTPP,and He's Yangchao recipe+PHTPP in vitro for 24 h,respectively.Ovarian histopathological changes were observed by hematoxylin-eosin(HE)staining,ATP levels were detected by luciferase assay,mtDNA copy numbers were detected by quantitative reverse transcriptase-polymerase chain reaction(qRT-PCR),mitochondrial structure changes were observed by transmission electron microscopy,protein and mRNA expression levels of estrogen receptor β(ERβ),peroxisome proliferator-activated receptor γ coactivator 1α(PGC1α),mitochondrial transcription factor A(TFAM),and superoxide dismutase 2(SOD2)were detected by Western blotting and qRT-PCR.Results:The ovarian tissue in model group exhibited few secondary and tertiary follicles,whereas the He's Yangchao recipe groups and Q10 group had abundant secondary and tertiary follicles.Compared with the blank control group,ATP and mtDNA levels in model group decreased(P＜0.01),mitochondrial crista disappeared or abnormal vacuolated structure increased;the protein and mRNA levels of ERβ,PGC1α,TFAM,and SOD2 decreased(all P＜0.01).ATP production increased in granulose cells of high-dose He's Yangchao recipe group and Q10 group;mtDNA copy numbers increased(P＜0.05 or P＜0.01);abnormal mitochondrial structure was reduced;the protein and mRNA expressions of ERβ,PGC1α,TFAM,and SOD2 increased(P＜0.05 or P＜0.01).Compared with the PHTPP intervention group,the proportion of normal mitochondrial structure in the granulose cells of He's Yangchao recipe+PHTPP group was higher;ATP content increased(P＜0.05 or P＜0.01);mtDNA copy numbers increased(P＜0.05 or P＜0.01);the protein and mRNA expression of ERβ,PGC1α,TFAM and SOD2 increased(P＜0.05 or P＜0.01).Conclusions:He's Yangchao recipe can regulate mitochondrial biogenesis through ERβ/PGC1α/TFAM pathway to improve ovarian function in POI mice.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To investigate the acoustic characteristics of speech prosody in patients after stroke and to select sensitive acoustic parameters of speech prosody.Methods A total of 30 patients after stroke(stroke group)and 30 healthy adults of similar age(control group)were collected.Both groups read short texts aloud,and each syllable and pause of all short sentences in the whole text were recorded under the spectrogram.Acoustic analysis was performed on the inter-rogative sentence"What do you want to buy for your grandson's birthday?"and the stressed sentence"I want to buy toys!"The rhythm(unnatural pause number,speech rate,articulation rate),intonation(whole sentence fundamental frequency,fundamental frequency standard deviation and fundamental frequency slope of interrogative sentences,boundary tone funda-mental frequency and fundamental frequency slope of interrogative sentences,fundamental frequency and fundamental fre-quency slope of four tones),and stress(average intensity of stressed syllables,peak intensity,and stressed syllables dura-tion)of speech prosody were analyzed and compared between the two groups.Results The unnatural pause number and the stressed syllables duration in the stroke group were significantly higher than those in the normal control group(P＜0.01).The speech rate,articulation rate,whole sentence fundamental frequency standard deviation,whole sentence funda-mental frequency slope,and fourth tone fundamental frequency slope in the stroke group were significantly lower than those in the normal control group(P＜0.01).The boundary tone fundamental frequency slope of interrogative sentences and the third tone fundamental frequency slope were significantly lower than those in the normal control group(P＜0.05).Conclu-sion Patients after stroke have poor rhythm control,manifested as excessive pauses and slow speech rate;insufficient into-nation expression,manifested as insufficient interrogative sentence tone,and poor control ability of the third and fourth tones;compensatory expression of stress,characterized by prolonging the expression time of stressed syllables.

Objective:To investigate the efficacy and safety of tocilizumab in the treatment of critically ill children with acute necrotizing encephalopathy (ANE).Methods:It is a retrospective cohort study. The children with ANE admitted to the pediatric intensive care unit of 4 Chinese tertiary hospitals from December 2022 to November 2023 were divided into conventional treatment group and tocilizumab group, and the comparison between groups was performed by using Mann ‐ Whitney U test or Chi-square test. Results:Among 21 cases of severe ANE, there were 11 males with the onset age of 65 (27, 113) months. The duration from onset to PICU admission was 2 (1, 2) days. There were 13 cases of ultra-high fever (greater than 40 ℃), including 18 cases of convulsions, and 19 cases with a GCS score of less than 8 points. The causative agent was novel coronavirus Omicron in 7 cases and influenza A in 14 cases. All cases had central respiratory failure requiring mechanical ventilation. Of the 21 cases, 18 were shock, 15 were coagulopathy, 10 were kidney injury and 13 were liver dysfunction. Of these hospitalized patients, 8 children with ANE were treated with tocilizumab. Eight cases received continuous blood purification (CBP) treatment, 5 of them were combined with plasmapheresis. Serum cytokine levels were elevated in 21 children with ANE, including (interleukin, IL)-6 and IL-8 (61 (22, 1 513) and 68 (5, 296) ng/L). There were 14 cases (67%) deaths, including 11 cases in the conventional treatment group and 3 cases in the tocilizumab group. There was no significant difference in the mortality rate between the two groups ( P=0.056). Tocilizumab-related rash or other adverse events were not observed. Conclusions:The motality of critically ill ANE patients was high. The combination of Tocilizumab with conventional treatment did not reduce the motality of severe ANE patients, and no adverse reactions of tocilizumab were observed.

The changes in epigenetic modifications of histones are one of the important factors in cancer development and metastasis,and the development of epigenetic therapies for cancer treatment has led to epigenetic drug screening as a research focus. In this work,the common methylation and acetylation modifications at the N-terminal of cellular histones H3 were quantified by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method,and a throughput assay for screening and assessment of epigenetic drug was established. A total of 39 kinds of modification combinations containing common methylation and acetylation sites of H3 peptides were simultaneously monitored by triple quadrupole mass spectrometry in multiple reaction monitoring (MRM) mode. The developed method was applied to analyze HepG2 cells exposed for 24 h to 28 kinds of epigenetic drugs that could modulate the level of methylation or acetylation modifications. Results showed that 25 of these drugs,such as deacetylase inhibitors Abexinostat,Valproic acid and AGK7,induced histone H3 modification changes in the exposed cells that were consistent with those reported in the literature,while other modification changes were also detectable. Three of these drugs,including demethylase inhibitors IOX1,GSK-j1 and acetyltransferase inhibitor L002,however,induced modification changes different from those reported in the literature. An overall test match rate of 89.3％ was achieved. The established LC-MS/MS method could quantitatively analyze histone H3 modification sites and their changes in cells in a high-throughput and highly sensitive manner,and could be applied to the evaluation of epigenetic drugs with known activities,with good specificity and rich modification information,which was expected to provide a new technological tool for screening and evaluation of epigenetically active compounds and exploration of their mechanism of action.

Professor ZHOU Peng has deeply discussed the pathological characteristics of psoriasis vulgaris,emphasizing that the disease is usually manifested deficiency interweaved with excess,leading to frequent recurrence and persistent refractory,which may lead to psychological and emotional problems of patients.This paper further expounds the effect of blood stasis on the pathogenesis,progression and prognosis of psoriasis,and puts forward a new method of combining Lingnan fire needling and filiform needling acupuncture technique to treat psoriasis vulgaris with blood stasis syndrome.Professor ZHOU Peng believes that the treatment principle of this disease is"regulating the mind first,rectifying blood as a base,syndrome differentiating and eliminating pathogenic factors",aiming at comprehensively considering the etiology and symptoms,in order to achieve more effective treatment results.Combined with the analysis of dermoscopic signs,it provides a possible improvement direction for the treatment of psoriasis vulgaris from a new perspective.

Objective To establish and forensically verify a 42 microhaplotypes(mircohaps,MHs)mul-tiplex assay system based on next-generation sequencing(NGS),and to explore the application value of this system in the practice of forensic genetics.Methods A total of 42 highly polymorphic MHs were selected from previous studies,and sequenced by the MiSeq FGxTM platform to verify the repeata-bility,sensitivity,specificity,stability,and mixture analysis ability of the detection system.Through population genetic investigation of 102 unrelated Chinese Han individuals in Liyang City,Jiangsu Province,China,the application value of this system in forensic genetics was evaluated.Results The sequencing repeatability of the 42-plex MHs assay was 100%and the sensitivity was as low as 0.062 5 ng.The system had the ability to withstand the interference of indigo(≤2 500 ng/μL),humic acid(≤9 ng/μL),hemoglobin(≤20 μmol),and urea(≤200 ng/μL)and to detect mixtures of 2 people(1∶19),3 people(1∶1∶9)and 4 people(1∶1∶1∶9).Based on 102 individual data,the combined power of discrimination and the combined power of exclusion were 1-3.45×10-30 and 1-3.77×10-11,respectively,and the average effect value of alleles was 2.899.Conclusion The 42-plex MHs assay was successfully established in this study and this system has high repeatability and sensitivity,good anti-jamming ability and mixture analysis ability.The 42 MHs are highly polymorphism and have good application value in individual identification and paternity testing.