Background The contamination of public baths with Legionella pneumophila contamination has become a growing public health concern in recent years. However, research on its association with bacterial community characteristics in water samples remains limited. The integration of 16S rRNA sequencing and random forest modeling provides a new approach to elucidate the bacterial community characteristics of public bath water and their association with Legionella pneumophila contamination. Objective To investigate the bacterial community structure and diversity of public bath water in Shanghai, explore the association between Legionella pneumophila contamination and bacterial community characteristics, and identify key bacterial genera associated with contamination, thereby providing a scientific basis for formulating hygiene management regulations for public bath water. Methods From February to March 2023, water samples were collected from ten public baths in Shanghai which were selected based on business scale, regional distribution, and functional differences. Water quality parameters were evaluated, and the samples were categorized into Legionella-positive and Legionella-negative groups based on the detection results of Legionella pneumophila. The bacterial community structure, α-diversity, and β-diversity were analyzed using 16S rRNA sequencing. Redundancy analysis (RDA) was employed to examine the relationship between physicochemical factors and bacterial community diversity. A random forest model was employed to identify key bacterial genera distinguishing the two groups, with the importance of genera being evaluated based on the mean decrease accuracy (MDA). Results The oxygen consumption in the Legionella-positive group was significantly lower than that in the Legionella-negative group (mean values: 1.85 mg·L⁻¹ vs. 6.81 mg·L⁻¹, P< 0.05), while no significant differences were observed in other physicochemical indicators. The sequencing results revealed a total of 27 bacterial phyla and 454 bacterial genera, with Proteobacteria (63.00%) being the dominant phylum. The dominant genera included Pelomonas (8.50%), Acidovorax (8.13%), Mycobacterium (7.93%), and Acinetobacter (6.59%). The α-diversity analysis indicated that bacterial community richness (Chao1 and ACE indices) was significantly higher in the Legionella-positive group than in the Legionella-negative group (P<0.01). The β-diversity analysis showed no significant difference in the bacterial community structure between the two groups (P>0.05). The RDA analysis demonstrated that the bacterial community diversity was positively correlated with pH and negatively correlated with oxygen consumption and free residual chlorine. The RDA1 and RDA2 explained 23.92% and 21.30% of the bacterial community diversity, respectively. The random forest model identified 20 key genera significantly influencing the microbial community distribution between the two groups, including unclassified_Bradyrhizobiaceae (MDA=2.42), Meiothermus (MDA=2.37), and Flavihumibacter (MDA=2.26). Conclusion The diversity of bacterial communities in public bath water is influenced by pH, oxygen consumption, and free residual chlorine. Samples contaminated with Legionella pneumophila exhibit greater microbial richness and contain characteristic key bacterial genera that contribute to community differences. Machine learning random forest technology helps identify these distinctive key bacterial genera. The findings provide a basis for carrying out risk early warning strategies in such settings.

ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground， the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows： out-of-capsule control， in-capsule control， model， and high （3.0 g·kg^-1） and low （1.5 g·kg^-1） doses of Taikong Yangxin Pills， and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. The obtained data were processed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group， the in-capsule control group showed elevated levels of thirteen metabolites， including 14-hydroxyhexadecanoic acid， linoleic acid， and α-linolenic acid （P<0.05）， which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group， the model group showed lowered levels of fourteen metabolites， including 4-imidazolone-5-propionic acid， isocitric acid/citric acid， and L-tyrosine （P<0.05）， which were recovered after the treatment with Taikong Yangxin pills （P<0.05）. The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine， tyrosine， and tryptophan biosynthesis， tyrosine metabolism， histidine metabolism， and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.

Currently, transcatheter intervention is the preferred treatment for patients with anatomically suitable atrial septal defects. However, the use of nickel-titanium alloy occluders in interventional procedures results in lifelong presence of the implant in the body, leading to complications such as metal allergies and arrhythmias in some patients. To overcome the short-term and long-term complications associated with the presence of metal, and to avoid radiation exposure and metal toxicity, this paper reports a case of successful transcatheter closure of atrial septal defect in a pediatric patient with metal allergies using fully biodegradable occluder under ultrasound guidance, achieving excellent results by interventional therapy.

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative.Isovalerylspiramycin Ⅰ(ISP Ⅰ)as a major component of carrimycin applied to upper respiratory infections,was first found to possess anti-fibrotic potential.The present study aims to evaluate the functions and mechanisms of ISP Ⅰ in protecting against liver fibrosis.According to our results,ISP Ⅰ not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation(BDL)rats and carbon tetrachloride(CCl4)mice.We proved that nucleotide-binding protein 2(NUBP2)was the direct target of ISP Ⅰ.ISP Ⅰ through targeting NUBP2,increased the amount of vascular non-inflammatory molecule-1(VNN1)on the cell membrane,which will inhibit oxidative stress and fibrosis.Simultaneously,the original carri-mycin's protective effect on liver damage and fibrosis was verified.Therefore,our study provides po-tential agents for patients with liver fibrosis-related diseases,and the clear mechanism supports wide application in the clinic.

OBJECTIVE: To explore the clinical and genetic characteristics of five fetuses with Harlequin ichthyosis (HI). METHODS: Five fetuses with HI diagnosed at Guangdong Women and Children Hospital between 2017 and 2024 were selected as study subjects. Clinical and laboratory data were collected and reviewed. Whole exome sequencing (WES) was carried out, and candidate variants were verified by bioinformatic analysis. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 202401024). RESULTS: The five fetuses had presented with ectropion, eclabium and contracture and flexion of fingers and toes. WES revealed that all had harbored compound heterozygous or homozygous variants of the ABCA12 gene. Among the eight types of variants, five were unreported previously. CONCLUSION The compound heterozygous or homozygous variants of the ABCA12 gene probably underlay the HI in the five fetuses. Clinicians should be vigilant about the possibility of HI in fetus with ectropion, eclabium, and contracture and flexion of fingers and toes.
Humans ; Ichthyosis, Lamellar/genetics* ; Female ; ATP-Binding Cassette Transporters/genetics* ; Pregnancy ; Genotype ; Phenotype ; Exome Sequencing ; Fetus ; Mutation ; Male ; Adult

Objective:To investigate the protective effects and mechanism of exogenous milk fat globule-epidermal growth factor 8(MFG-E8) on intestinal injury and ferroptosis in mice with acute pancreatitis (AP) and its mechanism.Methods:A total of 24 male C57 BL/6 mice were randomly divided into the normal control group, AP group, AP+ MFG-E8 group (MFG-E8 group), and AP+ MFG-E8+ cilengitide group (cilengitide group), with 6 mice in each group according to the random number table. The mice of normal control group were intraperitoneally injected with 0.9% sodium chloride solution. In the AP group, MFG-E8 group, and cilengitide group, the mice were intraperitoneally injected with 8% L-arginine twice at 1-hour intervals to induce the AP model. In the MFG-E8 group, mice were intraperitoneally injected with 20 g/kg of MFG-E8 at 2 hours after L-arginine injection. In the cilengitide group, mice were intraperitoneally injected with 20 mg/kg of cilengitide at 1 hour after the L-arginine injection, and 20 g/kg of MFG-E8 1 hour later. The mice were sacrificed and blood samples and intestinal tissues were collected at 72 hours after the first L-arginine injection. Hematoxylin-eosin staining was used to evaluate intestinal tissue injury. Myeloperoxidase (MPO) immunofluorescence staining was performed to detect neutrophils in intestinal tissues.Adenosinetriphosphate (ATP) levels were examined to detect changes in mitochondrial function. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were tested to check the level of intestinal oxidative stress. Dihydroethidium (DHE) fluorescent probe was used to label the oxygen free radicals in intestinal tissues. The expression of glutathione peroxidase 4 (GSH-Px4), solute carrier family 7 member 11 (also named xCT), and ferroptosos suppressor protein-1 (FSP-1) in intestinal tissues were detected by western blotting. Indepent-samples t-test, one-way ANOVA, and Student-Newman-Keuls test were performed for statistical analysis. Results:Intestinal tissue injury and inflammatory cell infiltration in mice were induced by intraperitoneal injection of L-arginine. Compared with those of AP model group, the intestinal pathology score, MPO fluorescence quantification and DHE fluorescence density of MFG-E8 group were significantly decreased (3.93±0.57 vs. 1.73±0.74, (26.33±4.49)/field vs. (11.00±3.27)/field, (39.67±5.79)/field vs. (12.33±3.68)/field), while the contents of ATP, MDA and SOD were increased ((77.09±8.52) μmol/g vs. (119.87±6.83) μmol/g, (0.10±0.01) μmol/g vs. (0.17±0.02) μmol/g, (105.67±6.93) U/mg vs. (144.49±18.55) U/mg), and the differences were statistically significant ( t=3.33, 3.93, 5.63, 8.77, 6.54, 4.38; all P<0.05). The results of Western blotting showed that GSH-Px4, xCT, and FSP-1 in the intestinal tissue of AP mice in the MFG-E8 group were all elevated compared with those of AP group, the relative expression levels were 1.22±0.19 vs. 0.55±0.09, 1.48±0.12 vs. 0.34±0.08, and 0.48±0.08 vs. 0.04±0.03, and the differences were statistically significant ( t=5.60, 14.39, 9.53; all P<0.05). Intraperitoneal injection of integrin αVβ3 receptor inhibitor cilengitide effectively antagonized the protective effects of MFG-E8 on intestinal injury in AP mice. Compared with MFG-E8 group, the histopathological score, MPO quantification and DHE fluorescence density of cilengitide group (3.53±0.50, (27.67±6.02)/field, and (31.33±3.86)/field, respectively) all increased, the expression of ATP, MDA and SOD were inhibited ((77.41±8.51) μmol/g, (0.19±0.04) mol/g, (100.46±8.15) U/mg); and GSH-Px4, xCT and FSP-1 all decreased, with the relative expression levels of 0.59±0.11, 0.16±0.06, and 0.10±0.03, respectively, and the differences were statistically significant ( t=3.02, 3.44, 5.04, 8.70, 4.01, 4.86, 5.05, 17.47, 8.34; all P<0.05). Conclusion:MFG-E8 alleviates intestinal oxidative stress and ferroptosis by integrin αVβ3 receptor, thereby reducing intestinal injury and inflammation in AP mice.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective:To investigate the effects of maternal antibiotics during the pre-natal period on the develop-ment of microglia and anxiety-like behaviors in offspring.Methods:Female SD rats were randomly divided into a maternal control group(CON-M)and a maternal antibiotic group(ABX-M),with 5 rats in each group.The antibiotic group received oral administration of compound antibiotics for 7 days before conception,and the control group received oral administration of the same dose of 0.9％saline during the same period.Subsequently,the two groups of female rats completed the pregnancy and delivery process at the same time,and their male offspring were retained and marked as the offspring control group(CON-O)and the offspring antibiotic group(ABX-O),respectively.The anxiety-like behaviors of offspring rats at 4 weeks and 8 weeks of age were evaluated by open field test and elevated plus maze test,respectively.The number and morphology of microglia in the hippocampus(HIP),cingulate gyrus(CG)and basolater-al nucleus of amygdale(BLA)of the brain of each group of offspring rats were detected by laser confocal microscopy im-aging.Results:The body weight and number of offspring were reduced in the ABX-M group.The 4-week-old ABX-O group showed an increase in anxiety-like behaviors,accompanied by an increase in the number and immature phenotype of microglia in the hippocampus,cingulate gyrus,and amygdala.Compared with the 8-week-old CON-O group,the 8-week-old ABX-O group showed obvious anxiety-like behaviors,and the number and immature phenotype of microglia in the hippocampus,cingulate gyrus,and amygdala of the brain continued to increase.Conclusion:Maternal antibiotic exposure during the pre-pregnancy period significantly affects the number and maturation of microglia in offspring,lead-ing to anxiety-like behaviors,and its effects can persist into adulthood.

Breast cancer remains a substantial threat to women's health and is one of the most prevalent malignant tumors in women.Because breast cancer onset is closely associated with female physiological characteristics,this article proposes that breast cancer be classified as a"women's miscellaneous diseases"and that its treatment be explored from this perspective.Drawing from Chapter 8 on Golden Chamber of Prescriptions for Miscellaneous Diseases in Women of Synopsis of Golden Chamber,the initial pathogenesis of breast cancer is associated with"emotional stress,improper lifestyle,deficiency,cold,and stagnation."The fundamental mechanism behind its formation is"blood cold accumulation and hardened masses."Specifically,emotional imbalance and improper lifestyle habits contribute to the combined invasion of the uterus by"deficiency,""accumulated cold,"and"stagnant qi."Over time,"cold-blood stasis accumulates at the uterine ostium,"and the cold and the stasis ascends from the uterus along the thoroughfare and conception vessels,obstructing the breast collaterals.This combination of yang qi stagnation and yin cold congealment,ultimately leads to the development of breast cancer.The treatment principle should focus on"activating yang and dispersing cold."A therapeutic approach centered on Wenjing Decoction combined with Xiaoyao Powder can be adapted based on the stage and type of breast cancer while also considering the dynamic interplay between pathogenic factors and healthy qi,along with shifts in deficiency and excess patterns of disease.By adhering to the principles of consistency and flexibility and integrating disease and syndrome differentiation,the goal is to develop precise and personalized treatment strategies to improve clinical outcomes.

Objective:To investigate the clinicopathological features of advanced-stage mycosis fungoides (MF).Methods:A retrospective case-series study was conducted. The clinical data of 5 cases diagnosed with advanced-stage MF in Chengdu Second People's Hospital between January 2015 and July 2023 were analyzed. The clinicopathological features of patients were summarized.Results:There were 2 males and 3 females in 5 MF patients, with the median age of 55 years (45-86 years) and the medical history of 2-16 years. The main symptoms were pruritus and erythema. The lesions were presented by erythema, scales, plaques, blisters, erosion, ulcers, pigmentation, nodules, and erythroderma. Histopathological examination showed different skin lesion patterns such as psoriasis-like, interfacial dermatitis, non-infectious granuloma, deep and shallow perivascular dermatitis, tumors. Among 5 patients, 1 case was mycosis fungoides bullosa, 2 cases were erythrodermic MF, 1 case was granulomatous MF, and 1 case was classical MF. Lymphocyte epidermis was found in 4 cases, cytoplasmic halos cells lined up along the basal layer of the epidermis and Pautrier microabscess were found in 3 cases, large-cell transformation was found in 1 case. Tumor cells were positive for CD3, CD4 and negative for CD8, CD56, ALK and CD20; EBER 1/2 hybridization in situ was negative. CD30 was positive in transformed large cells and T cell receptor gene rearrangement was positive. The tumor cells were detected in bone marrow and peripheral blood of 2 cases and in cerebrospinal fluid of 1 case. Head magnetic resonance imaging of 1 case indicated abnormal signal nodules in the right temporal region and the normal architecture of the lymph nodes in 2 cases was completed destroyed by malignant cells. TNMB stage: 2 cases were in stage Ⅱ B, 2 cases were in stage Ⅳ A2, and 1 case was in stage Ⅳ B. Interferon α-based systemic therapy was performed in 1 case, 2 cases received chemotherapy or combined with intrathecal injection and radiotherapy, and other 2 cases were not treated. All of them just achieved partial remission. Finally, 1 case died of sudden cardiac death, 2 cases died of lung infection, and 2 cases survived with tumors. Conclusions:Advanced-stage MF is presented with different skin lesion manifestations and histopathologic changes. Multidisciplinary combined management helps the diagnosis and treatment of MF.