The gut microbiota is regarded as the "eighth organ" of the human body and plays a critical regulatory role in the occurrence and progression of various diseases. Ulcerative colitis （UC） is a chronic inflammatory bowel disease with a complex etiology and a tendency toward recurrent episodes. In recent years， studies have shown that gut microbiota dysbiosis plays a key role in its pathological processes. Meanwhile， an increasing number of studies have demonstrated that imbalances in the gut microbiota and abnormalities in its metabolites are closely associated with the development of atrial fibrillation （AF）. Although UC and AF belong to diseases of the digestive system and cardiovascular system， respectively， both exhibit systemic inflammatory characteristics and are often accompanied by gut microbiota dysregulation and abnormal metabolic products. However， systematic investigations into the mechanisms by which gut microbiota-derived metabolites act in these two diseases remain limited. Based on this， the present study adopts literature review and theoretical analysis methods， taking the "gut microbiota-gut-heart" axis as the entry point， to systematically summarize the signaling networks of three key classes of metabolites， i.e.， short-chain fatty acids （SCFAs）， bile acids （BAs）， and trimethylamine N-oxide （TMAO）， in the comorbidity mechanism of UC and AF. The findings indicate that these metabolites may activate key inflammatory pathways， such as NF-κB and NLRP3， thereby synergistically mediating intestinal barrier dysfunction and systemic inflammation and constructing a potential comorbidity network. On this basis， potential intervention strategies for the treatment of UC-AF comorbidity， including probiotic intervention and fecal microbiota transplantation， are further discussed. This study aims to provide new theoretical evidence and research perspectives for prevention and treatment strategies of cross-system diseases.

ObjectiveTo meet the requirements of Good Laboratory Practice (GLP), Sichuan Institute for Drug Control (Sichuan Testing Center of Medical Devices, Sichuan Institute of Musk Deer Breeding) Safety Evaluation Center (hereinafter referred to as the center) conducts a targeted validation study to address the lack of supporting data for the specified validity periods of disinfectants, feed, and bedding during their use in laboratory animal facilities. The study summarizes practical experience in material management and provides a scientific basis for the standardized management of materials in the facility. MethodsUnder the routine operating conditions of the laboratory animal facility at the center, the disinfection efficacy of four commonly used disinfectants was confirmed using the quantitative suspension kill test, with the disinfectants tested on day 0, day 7, and at 1, 2, and 3 months after preparation and after opening; for laboratory animal feed, nutritional components, chemical contaminants, and microbial indicators were tested 7 days after opening; microbial indicators of laboratory animal corncob bedding were tested after storage for 7 days following opening and sterilization. ResultsUnder the GLP management system of our center, the disinfection efficacy log reduction values of prepared 0.04% sodium hypochlorite solution, 0.1% didecyldimethylammonium bromide solution, and 0.2% benzalkonium bromide solution were all ≥5 on days 0 and 7. The log reduction values of opened 75% ethanol were ≥5 on days 0 and 7 and at 1, 2, and 3 months after opening. All disinfectants were therefore qualified and effective. Compared with the factory inspection data, the nutritional components, chemical contaminants, and microbial indicators of SPF-grade rat and mouse maintenance feed, SPF-grade guinea pig growth and reproduction feed, conventional-grade guinea pig growth and reproduction feed, rabbit maintenance feed, and dog maintenance feed showed a slight overall downward trend but no significant differences 7 days after opening. The microbial indicators of specialized corncob bedding for SPF-grade laboratory animals stored for 7 days after opening and conventional-grade corncob bedding stored for 7 days after sterilization showed no significant fluctuations. All indicators still met the relevant requirements of GB/T 14924.2—2001 Laboratory Animals—Hygienic Standard for Formula Feeds and GB 14924.3—2010 Laboratory Animals—Nutrients for Formula Feeds. ConclusionBased on practical experience in managing the center's GLP laboratory animal facility and validation of core quality indicators, the specified validity periods of disinfectants, feed, and bedding meet the quality requirements, providing a practical reference for the standardized management of laboratory animal facilities.

Objective To investigate the value of constructing a risk prediction model of brain metastasis in lung cancer based on clinical-CT imaging.Methods The clinical and CT imaging data of 208 patients with lung cancer confirmed by surgical pathology or puncture biopsy were analyzed retrospectively,including 98 patients in the metastasis group and 110 patients in the non-metastasis group.Univariable and binary logistic regression analyses were performed between the two groups,and the clinical,CT imaging,and clinical-CT imaging models were constructed according to the selected independent risk factors.Prediction model performance was eval-uated with receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA).Results Multivariate analysis showed that T stage,pathological type,radiotherapy and chemotherapy,surgery,long diameter(LD),short diameter(SD),minimum CT value(CTmin)were the independent risk factors for predicting brain metastasis in lung cancer(P<0.05).The area under the curve(AUC)of clinical,CT imaging and clinical-CT imaging models were 0.925,0.764,0.941,respectively.DeLong test analysis showed that the AUC of clinical-CT imaging model,clinical model and CT imaging model was statistical difference(Z=2.093,5.777,all P<0.05).The calibration curve suggested a good fit of the clinical-CT imaging model.The DCA suggested that the clinical-CT imaging model demonstrates good clinical benefits.Conclusion The clinical-CT imaging model can effectively predict the occurrence of brain metastasis in lung cancer,which is helpful to guide the development of accurate diagnosis and treatment plan.

Objective:To analyze the clinical features and genetic sequencing results of a patient with Kallmann syndrome(KS) carrying digenic mutations who initially presented with osteoporosis, and to enhance awareness of this disease phenotype.Methods:Clinical data were collected, and peripheral blood DNA was extracted for whole-exome sequencing. Relevant literature was reviewed to summarize phenotypes associated with digenic/oligogenic variants involving CHD7.Results:The patient exhibited back pain, delayed development of secondary sexual characteristics, and hyposmia. Laboratory tests revealed reduced sex hormones and gonadotropin levels, while pituitary imaging was unremarkable. Bone mineral density imaging confirmed osteoporosis, and thoracolumbar X-rays showed multiple vertebral compression fractures. Genetic analysis identified a heterozygous splice-site mutation in CHD7(c.2698-1G>T) and a heterozygous missense mutation in WDR11(c.439G>A: p.D147N). According to ACMG criteria, the CHD7 mutation was classified as pathogenic, while the WDR11 variant was defined as a variant of uncertain significance(VUS). Literature review indicated that 40% of KS patients with digenic/oligogenic variants involving CHD7 presented with hearing or ocular abnormalities.Conclusion:This study reports a novel CHD7 mutation and a previously undescribed digenic combination of CHD7 and WDR11 variants in a KS patient. CHD7 variants may be implicated in auditory or ocular involvement in KS cases with digenic/oligogenic inheritances. KS patients may also manifest skeletal abnormalities in addition to hypogonadotropic hypogonadism. Tailored management of sex hormones and osteoporosis therapies across life stages is essential for optimizing bone health in KS.

Objective To evaluate the effects of the method of blood-cooling and blood stasis-resolving on heart function and prognosis in patients with sepsis-induced myocardial dysfunction(SIMD).Methods Sixty patients with SIMD admitted to the department of critical care medicine of Affiliated Hospital of Nanjing University of Chinese Medicine from June 2022 to October 2024 were enrolled as study subjects.The patients were divided into treatment group and control group according to random number table,with 30 patients in each group.All patients received conventional treatments,the patients in the treatment group were given Taohe Chengqi decoction(Persicae Semen 12 g,Chinese rhubarb 12 g,Cinnamon twig 6 g,Licorice root 6 g and Sodium Sulfate 6 g),the decoction was concentrated to 200 mL and taken in 2 divided doses in the morning and evening,one dose daily;and the patients in the control group were given the same amount of warm water.The total course of treatment lasts for 7 days.The differences in indicators of cardiac function[brain natriuretic peptide(BNP),cardiac troponin I(cTnI),MB isoenzyme of creatine kinase(CK-MB),aspartate aminotransferase(AST)]and echocardiographic parameters[left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),mitral orifice early/late diastolic blood flow velocity ratio(E/A ratio),E/mitral and tricuspid valve ostia and the peak early diastolic velocity(E/e')]at admission,at 1st and 7th day after treatment,and prognosis indexes[mechanical ventilation time,intensive care unit(ICU)length of stay,total hospital stay,28-day survival rate]were compared between two groups.Draw the Kaplan-Meier survival curve and compare the difference in the 28-day cumulative survival rate between the two groups of patients.Results After 7 days therapy,LVEF of the treatment group was significantly higher than that the control(0.524±0.132 vs.0.458±0.118,P<0.05)and E/e'ratio of the treatment group was significantly lower than the control group[11.17(9.57,12.04)vs.11.82(11.28,13.72),P<0.05].There were no significant differences in the 28-day mortality and total hospital stay time between the two groups,but mechanical ventilation time[days:7.00(0.00,11.00)vs.12.50(3.50,21.75),P<0.05]and stay time of ICU[days:14.50(7.75,25.00)vs.21.00(14.25,31.50),P<0.05]in the treatment group were shorter than those in the control group.The Kaplan-Meier survival showed that the cumulative 28-day survival rate was similar between two groups(Log-Rank:χ2=1.448,P=0.229).Conclusion The method of blood-cooling and blood stasis-resolving could decrease mechanical ventilation time and length of stay in ICU of SIMD patients and could increase LVEF in the treatment group.

Objective:To analyze the functional outcomes of arthrodesis for the first metatarsophalangeal joint.Methods:A retrospective study was conducted to analyze the 21 patients who had undergone arthrodesis for the first metatarsophalangeal joint at Department of Foot and Ankle Surgery, Beijing Jishuitan Hospital from August 2013 to October 2019. The cohort included 6 males and 15 females. One patient underwent bilateral surgery, 10 cases the left side surgery and 10 cases the right side surgery. Their ages averaged (63.1±9.2) years. There were 12 cases of simple hallux valgus, 5 cases of rheumatoid arthritis combined with hallux valgus, and 4 cases of gout combined with hallux valgus. The visual analog scale (VAS) pain score, American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score, foot function index (FFI) score, hallux valgus angle (HVA), and intermetatarsal angle (IMA) were compared between preoperation and the last follow-up. The proximal phalangeal inclination angle (PPIA) was measured postoperatively. Postoperative satisfaction was evaluated using the Coughlin rating scale. Complications were documented.Results:All patients were followed up for 71.0 (69.8, 75.0) months. In all patients at the last follow-up, VAS [1(0, 3) points], FFI [4.8 (1.6, 8.6) points], HVA [23.4° (14.3°, 28.5°)], and IMA (9.6°±3.2°) were significantly lower than the preoperative values [4 (3, 7) points, 30.4 (16.7, 46.8) points, 43.5° (31.5°, 48.2°), and 13.0°±4.5°], and the AOFAS forefoot score [80.0 (70.8, 90.0) points] was significantly higher than the preoperative one [46.0 (32.8, 55.3) points] ( P<0.05). The postoperative PPIA was 7.7°±10.1°. According to the Coughlin rating scale, 12 cases were rated as excellent, 5 as good, 2 as fair, and 3 as poor. All patients reported relief from painful plantar calluses, most ones experienced complete resolution of plantar calluses, and some ones had stiffness of the metatarsophalangeal joint after fusion. Conclusion:Arthrodesis for the first metatarsophalangeal joint is a reliable treatment for degenerative changes in the metatarsophalangeal joint, because it can well restore the postoperative foot function, significantly relieve pain, and lead to high patient satisfaction.

Eosinophilic gastroenteritis(EG)is a rare disease characterized by abnormal infiltration of eosinophils(Eos)in gastrointestinal tissues.Due to the unclear pathogenesis of EG and the lack of effective therapeutic drugs,research on its novel mechanisms,targets and drugs is critical.This article starts by outlining the research progress in the pathogenesis of EG,involving IgE mediated typeⅠimmediate allergic reactions and T helper 2 cell(Th2)mediated delayed allergic reactions.Then,the related targets of EG are summarized,including Th2 cytokines and factors regulating Eos function,but there has been no breakthrough in the treatment of these targets.Finally,the therapeutic drugs for EG are reviewed,such as glucocorticoids,antiallergic drugs and biologics.The advantages and disadvantages of various drugs are also described.However,these drugs cannot meet the current demands of clinical treatment and there is an urgent need to develop novel therapeutic drugs.It is believed that multi-target therapy is an ideal treatment for EG,and that traditional Chinese medicine and natural products should be the priorities of research and development for EG therapeutic drugs in the future.This review is expected to provide new ideas for the clinical treatment strategies and drug development of EG.

OBJECTIVE To investigate the effect of salvianolic acid A(SAA)on functions of neutro-phils after activation in vitro.METHODS Rat neutrophils were extracted and activated by lipopolysac-charide(LPS)at 0.3,1,3 mg·L-1,and the number of adherent neutrophils and myeloperoxidase(MPO)activity were detected to determine the concentration of LPS.Neutrophils were divided into the control,model,model+4-aminobenzohydrazide(ABH)20 μmol·L-1,and model+SAA 1,3 and 10 μmol·L-1 groups.LPS was stimulated with 3 mg·L-1 for 30 min,and the neutrophil adhesion rate was detected by immunofluorescence after 1 h of drug incubation.After 2 h of drug incubation,phagocytosis of neutro-phils was detected by immunofluorescence and fluorescein isothiocyanate-immunoglobulin G.After 3 h of drug incubation,the neutrophil adhesion rate to endothelial cells was detected by colorimetric assay.Intracellular MPO activity and hypochlorous acid(HOCl)production were investigated by colorimetric assay in response to the degranulation function.Intracellular reactive oxygen species(ROS)levels were detected by probe assay,and mitochondrial membrane potential by JC-1 assay.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)and total antioxidant capacity(T-AOC)were measured to reflect oxidation function of neutrophils.RESULTS LPS increased the number of adherent cells and MPO activity in a concentration-dependent manner,with 3 mg·L-1 of LPS showing the most significant effect,which was used for subsequent experiments.Compared with the control group,LPS-activated neutrophil adhesion and phagocytosis were significantly enhanced.MPO activity and HOCl production significantly increased.The levels of ROS and MDA in LPS-activated neutrophils were significantly increased while the mitochondrial membrane potential and the levels of SOD,GSH,T-AOC were significantly decreased,indicating that the oxidative stress ability was enhanced.Compared with the model group,SAA dose-dependently inhibited LPS-induced adhesion,phagocytosis,degranu-lation,and ROS generation of neutrophils,with significant effects at medium and high doses.CONCLU-SION SAA can inhibit different functions of neutrophils after activation,which may be a potential drug for targeting neutrophil function regulation.

Objective To investigate the value of constructing a risk prediction model of brain metastasis in lung cancer based on clinical-CT imaging.Methods The clinical and CT imaging data of 208 patients with lung cancer confirmed by surgical pathology or puncture biopsy were analyzed retrospectively,including 98 patients in the metastasis group and 110 patients in the non-metastasis group.Univariable and binary logistic regression analyses were performed between the two groups,and the clinical,CT imaging,and clinical-CT imaging models were constructed according to the selected independent risk factors.Prediction model performance was eval-uated with receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA).Results Multivariate analysis showed that T stage,pathological type,radiotherapy and chemotherapy,surgery,long diameter(LD),short diameter(SD),minimum CT value(CTmin)were the independent risk factors for predicting brain metastasis in lung cancer(P<0.05).The area under the curve(AUC)of clinical,CT imaging and clinical-CT imaging models were 0.925,0.764,0.941,respectively.DeLong test analysis showed that the AUC of clinical-CT imaging model,clinical model and CT imaging model was statistical difference(Z=2.093,5.777,all P<0.05).The calibration curve suggested a good fit of the clinical-CT imaging model.The DCA suggested that the clinical-CT imaging model demonstrates good clinical benefits.Conclusion The clinical-CT imaging model can effectively predict the occurrence of brain metastasis in lung cancer,which is helpful to guide the development of accurate diagnosis and treatment plan.

BACKGROUND:Mammary stem cells are vital for the development and homeostasis of mammary gland tissue.The occurrence of breast cancer has a close relationship with the mammary stem cells.Recent studies have shown that Hopx,as an important transcriptional regulator of morphogenesis and cell differentiation,has been confirmed to be expressed in a variety of adult stem cells such as nerves,intestines,hair follicles and lungs.However,its role in mammary stem cells has not been reported so far.OBJECTIVE:To investigate whether Hopx expression marks mammary stem cells.METHODS:(1) Female Hopx-LacZ transgenic mice aged 8 weeks were selected to detect the background expression of Hopx in breast tissue by β-galactosidase staining.(2) Female wild-type mice at 4,6,and 8 weeks of age and 14.5 days of gestation were selected for whole-tissue magenta staining and K14 and K8 immunofluorescence staining,respectively.(3) Female Hopx-CreERT2;Rosa26LacZ transgenic mice aged 8 weeks and 17.5 days of gestation were selected and stained with breast β-galactosidase.(4) The 4-week-old female Hopx-CreERT2;Rosa26LacZ transgenic mice were selected.The Cre/loxp system was activated by intraperitoneal injection of tamoxifen (once every other day,three times),and breast β-galactosidase staining was performed 4 weeks after injection.The 8-week-old female Hopx-CreERT2;Rosa26LacZ transgenic mice were selected.The Cre/loxp system was activated by intraperitoneal injection of tamoxifen (once every other day,three times),and breast β-galactosidase staining was performed 4 and 10 weeks after the last injection.(5) Female Hopx-CreERT2;Rosa26LacZ transgenic mice aged 8 weeks were selected.The Cre/loxp system was activated by intraperitoneal injection of tamoxifen (once every other day,three times).Hopx-CreERT2;Rosa26LacZ transgenic mice were pregnant 2 weeks after injection.The mammary tissue of mice at 17.5 days of the first pregnancy and 17.5 days of the third pregnancy was stained with β-galactosidase.RESULTS AND CONCLUSION:(1) The results of β-galactosidase staining showed that the mammary ducts of Hopx-LacZ transgenic mice at 8 weeks of age did contain Hopx-positive cells and were located in the basal epithelia,with a small number.(2) Whole-mount staining of mammary glands and immunofluorescence staining results exhibited that the mammary glands of mice had different characteristics with corresponding developmental stages such as puberty,maturity,and pregnancy,and underwent a series of complex epithelial remodeling processes.(3) The results of β-galactosylase staining showed that Hopx-labeled positive cells in the mammary duct of Hopx-CreERT2;Rosa26LacZ transgenic mice at 17.5 days of gestation increased compared with female Hopx-CreERT2;Rosa26LacZ transgenic mice at 8 weeks of age.(4) The results of β-galactosylase staining showed that the Hopx-labeled positive cells in the mammary glands of 4-and 8-week-old female Hopx-CreERT2;Rosa26LacZ transgenic mice after tamoxifen injection were located in the basal epithelium with a small number.(5) The results of β-galactosidase staining showed that Hopx-labeled positive cells in the mammary glands of mice at 17.5 days of the first and third gestation were located in the basal epithelia around the alveoli,and the number of Hopx-labeled positive cells at 17.5 days of the third gestation was more.(6) In conclusion,Hopx reporter-marked basal epithelial cells belong to dormant mammary stem cells,which are responsible for the growth of the mammary glands during pregnancy and contribute to acinar formation.