ObjectiveTo investigate the role of the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway in intestinal mucosal barrier damage in ulcerative colitis， as well as the intervention mechanism of Shaoyaotang. MethodsSixty SD rats were allocated into a blank group， a model group， a mesalazine （0.42 g·kg^-1） group， and low-， medium-， and high-dose （11.1， 22.2， 44.4 g·kg^-1， respectively） Shaoyaotang groups. A model of ulcerative colitis was induced by 2，4，6-trinitrobenzenesulfonic acid （TNBS）. After successful modeling， rats were administrated with corresponding agents via gavage for 7 days. Changes in colon length and colon weight were observed. Hematoxylin-eosin staining was performed to examine the pathological changes of the colon， and immunohistochemistry was employed to detect the expression of the inflammatory cytokine interleukin-8 （IL-8）， cyclooxygenase-2 （COX-2）， junction adhesion molecule-1 （JAM-1）， and claudin-1 in the colon. Western blot analysis was performed to determine the protein levels of TLR4， MyD88， and NF-κB in the colon. ResultsCompared with the blank group， the model group showed elevated DAI score （P<0.01）， reduced colon length and colon weight （P<0.01）， down-regulated protein levels of JAM-1 and claudin-1 （P<0.01）， and up-regulated protein levels of IL-8， COX-2， TLR4， MyD88， and NF-κB p65 （P<0.01） in the colon tissue. Compared with the model group， each treatment group showed decreased DAI score （P<0.05， P<0.01）， increased colon length and colon weight （P<0.05， P<0.01）， up-regulated protein levels of JAM-1 and claudin-1 （P<0.01）， and down-regulated protein levels of IL-8， COX-2， TLR4， MyD88， and NF-κB p65 （P<0.01） in the colon tissue. ConclusionShaoyaotang alleviates intestinal inflammation and intestinal mucosal damage to protect intestinal barrier integrity by regulating the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo observe the clinical efficacy of electroacupuncture in treatment of simple obesity patients and its effects on the metabolism-inflammation network. MethodsSeventy-two patients with simple obesity were randomly divided into a electroacupuncture group and a sham electroacupuncture group， with 36 patients in each group. In the electroacupuncture group， conventional acupuncture was applied at Zhongwan （CV 12）， bilateral Tianshu （ST 25）， bilateral Daheng （SP15）， Qihai （CV 6）， Guanyuan （CV 4）， bilateral Zusanli （ST 36） and Fenglong （ST 40）. The sham electroacupuncture group used placebo needle at same acupoints as the electroacupuncture group. Both groups were given sparse-dense waves with a frequency of 2/10 Hz， 30 minutes per session， 3 times a week， for a total of 8 weeks of treatment. The changes of human body parameters including body weight， body mass index （BMI）， waist circumference， and body fat percentage （BFP）， metabolic factors including serum fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol （TC）， high density lipoprotein （HDL）， low density lipoprotein （LDL）， leptin， and ghrelin， and inflammatory factors including interleukin-6 （IL-6） and tumor necrosis factor α （TNF-α） were compared before and after treatment. Correlations between changes in leptin， ghrelin and inflammatory factors were further analyzed. ResultsWaist circumference was significantly reduced after treatment in both groups compared with baseline （P＜0.05）， and the post-treatment waist circumference was lower in the electroacupuncture group than in the sham electroacupuncture group （P＜0.05）； body weight， BMI and BFP decreased significantly after treatment compared to pretreatment levels in the electroacupuncture group （P＜0.05）. Serum leptin， IL-6 and TNF-α declined significantly after treatment in both groups versus baseline （P＜0.05）； the electroacupuncture group had lower post-treatment levels of leptin， IL-6 and TNF-α as well as larger pre-post changes than the sham group （P＜0.05）； ghrelin increased markedly after treatment in both groups （P＜0.05）， with higher post-treatment ghrelin and greater pre-post variation observed in the electroacupuncture group （P＜0.05）. In the electroacupuncture group， changes in ghrelin were negatively correlated with IL-6 and positively correlated with TNF-α （P＜0.01）； in the sham electroacupuncture group， ghrelin changes were negatively correlated with both IL-6 and TNF-α， whereas leptin changes were positively correlated with the two inflammatory markers （P＜0.01）. ConclusionElectroacupuncture can effectively improve clinical manifestations， as well as regulate serum metabolic and pro-inflammatory factors in patients with simple obesity， and discrepant correlation patterns of metabolism-inflammation are observed between the two groups.

Objective To analyze the clinical distribution,drug resistance characteristics,molecular prevalence,and impact of immunocompromised status on the infection rate of carbapenem-resistant Enterobacteriaceae(CRE)isolated from pediatric respiratory tract samples(sputum,bronchoalveolar lavage fluid).Methods A retrospective analysis was conducted on clinical data of hospitalized children from 2019 to 2023.A total of 1 235 non-repetitive strains of Enterobacteriaceae bacteria were obtained from pediactric respiratory tract samples.Drug susceptibility testing,multilocus sequencing typing(MLST),and resistance-related gene sequencing were performed on 100 isolated CRE strains,to study the clinical distribution,drug resistance characteristics,and molecular prevalence of CRE,and to further analyze the impact of immunocompromised status on the respiratory CRE infection rate in children.Results From 2019 to 2023,the detection rate of CRE in 1 235 strains of Enterobacteriaceae bacteria was 8.10%(100/1 235).Among them,51.0%(51/100)of CRE were isolated from the intensive care unit(ICU),of which 33.0%(33/100)were isolated from the Surgical ICU,18.0%(18/100)of CRE was isolated from the Medical ICU;32.0%(32/100)of CRE were isolated from Department of Neonatology,with the majority(74.0%)isolated from infants under 6 months of age.Of all pediatric patients,85.0%recovered and were discharged after treatment.Immunocompromised status was identified as an independent risk factor for CRE infection.Among 100 strains of CRE,Carbapenem-resistant Klebsiella pneumoniae(CRKP)was the most commonly detected strain,accounting for 88.0%(88/100),followed by Escherichia coli at 6.0%(6/100)and Enterobacter cloacae at 4.0%(4/100).CRE strains were highly resistant to carbapenems and cephalosporins,with prevalent resistance to amikacin,ciprofloxacin,and levofloxacin.However,their resistance rates were relatively low to tigecycline,colistin,minocycline,ceftazidime/avibactam,meropenem/vaborbactam,and imipenem/relebactam.The screening results of carbapenem resistance genes showed that blaKPC-2 was the most prevalent gene(74.0%),followed by blaNDM-1(14.0%)and blaNDM-5(11.0%).Molecular typing showed that ST11 type CRE was the dominant type,comprising 72.0%(72/100)and was the primary epidemic clone.Conclusions CRKP is the most prevalent CRE strain isolated from pediatric respiratory tract samples,primarily identified in the ICU,Department of Neonatology,and among infants under 6 months of age.Immunocompromised status is an independent risk factor for respiratory CRE infection in children.CRE generally has high resistance to antibacterial drugs,with blaKPC-2 being the dominant resistance genotype,and ST11 as the predominant multilocus sequence type.Clinical management should account for these characteristics to implement timely interventions and rational therapeutic strategies.

Tumor-targeted therapy is a vital approach in precision medicine,selection of target molecule is a key element in tumor-targeted therapy.B7-H3(CD276),as an immune checkpoint molecule selectively highly expressed on tumor cells,is a crucial molecule involved in regulation of tumor immunity.Numerous recent studies have found that B7-H3,in addition to its immune check-point function,also participates in regulation of malignant biological behaviors of tumor cells and is considered to have great potential as a pan-cancer universal drug target.Current immunotherapeutic strategies targeting B7-H3 primarily include development of block-ing monoclonal antibodies(Blocking mAb),antibody-drug conjugate(ADC),chimeric antigen receptor(CAR)T/NK cell therapies,monoclonal antibody dependent cellular cytotoxicity(ADCC)drugs,radionuclide drug conjugates(RDC),bispecific/trispecific anti-body(BsAb/TriAb),and antibody cytokine drug combinations,among others.These strategies aim to enhance body's immune re-sponse to cancer through various mechanisms,thereby inhibiting tumor growth and metastasis.Multiple preclinical and clinical studies have shown that immunotherapy targeting B7-H3 has potential therapeutic value.Therefore,this article mainly reviews the latest status of development of tumor immunotherapy drugs targeting B7-H3 molecule.

Objective:To investigate whether hysteroscopic transcervical resection of septum (TCRS) prior to in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) can improve cumulative live birth rates in patients with uterine septum. Methods:A retrospective cohort study was conducted to analyze data from 244 patients with partial uterine septum who underwent IVF/ICSI at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University between January 2016 and August 2022. The patients were divided into a surgical group ( n=171) and a non-surgical group ( n=73) based on whether TCRS was performed prior to IVF/ICSI. The clinical outcomes of IVF/ICSI in the two groups were analyzed, with the primary observation indicator being the cumulative live birth rate. Cox regression analysis was employed to identify determinants. Results:The age of patients in the operated group [(31.20±3.80) years] was younger than that in the non-operated group [(32.92±5.34) years, P=0.005], and the basal antral follicle count [17.0 (11.0, 24.0)] was higher than that in the non-operated group [14.0 (8.0, 21.5), P=0.039]. There were no significant differences in other baseline data (all P>0.05). The cumulative pregnancy rate [79.53% (136/171)] and the cumulative live birth rate [60.23% (103/171)] in the operated group during the 24-month follow-up period were significantly higher than those in the non-operated group [65.75% (48/73), P=0.022; 45.21% (33/73), P=0.030]. Compared with the operated group [296.0 (260.0, 430.0) d], the duration from the start of ovarian stimulation to the first live birth was significantly prolonged in the non-operated group [379.0 (329.5, 471.5) d, P<0.001]. Adjusted Cox-regression analysis showed that whether or not surgery was performed ( HR=1.683, 95% CI: 1.116-2.539, P=0.013) and the basal antral follicle count ( HR=1.032, 95% CI: 1.000-1.065, P=0.048) were independent factors affecting cumulative live birth rate. Conclusion:Performing TCRS before IVF/ICSI can improve cumulative live birth rates of patients with uterine septum.

Objective To investigate the antimicrobial resistance patterns of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains isolated from children for better prevention,treatment,and control of CRKP infections in children.Methods A total of 182 clinical CRKP strains were collected between January 2018 and December 2020 in Hebei Children's Hospital.All CRKP strains were identified by matrix-assisted laser desorption ionization-time of flight(MALDI-TOF)mass spectrometry.The common carbapenemase genes(blaKPC,blaNDM,blaIMP,blaVIM,blaOXA-48)of CRKP isolates were studied by PCR.Multilocus sequence typing(MLST)was performed for homology analysis.Results The 182 children infected with CRKP were mainly infants(＞28 days to＜1 years),accounting for 49.45％(90/182),followed by newborns(≤28 days),accounting for 36.26％(66/182).The main source of the 182 CRKP isolates was sputum(50.55％,92/182),blood(15.93％,29/182),and urine(13.19％,24/182).The strains were mainly isolated from patients in neonatology(30.22％,55/182),general surgery(21.43％,39/182),cardiac surgery(13.19％,24/182),and intensive care unit(11.54％,21/182).Antimicrobial susceptibility testing showed that all of the 182 CRKP strains were resistant to cefepime,ceftazidime,piperacillin-tazobactam,and cefoperazone-sulbactam(100％).Overall,97.8％,71.4％,81.9％,75.8％,69.2％,and 2.7％of the strains were resistant to aztreonam,amikacin,ciprofloxacin,levofloxacin,doxycycline,and tigecycline,respectively.The prevalence of carbapenemase gene blaKPC-2 was the highest(73.63％,134/182),followed by blaNDM-5(15.38％,28/182),and blaNDM-1(11.54％,21/182).A total of 15 different sequence types(ST)were identified by MLST,of which ST11 was the most common type(72.53％,132/182),followed by ST17(11.54％,21/182).Conclusions CRKP isolates in Hebei Children's Hospital showed high level resistance to antimicrobial agents.Antimicrobial therapy should be prescribed cautiously according to the results of antimicrobial susceptibility testing to avoid the emergence of resistant strains.KPC-2-producing ST1 1 type CRKP strains may be prevalent in this hospital.Effective control measures should be taken to avoid further spread of such CRKP strains.

Objective:To analyze the clinicopathological factors affecting the prognosis of patients after curative resection of lung metastases (LMs) from colorectal cancer (CRC) and to construct a clinical risk scoring (CRS) model.Methods:This study retrospectively collected clinicopathological data and follow-up information on 132 patients who underwent radical resection of LMs from CRC at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2010 and December 2020. We analyzed the clinicopathological factors influencing patient prognosis using univariate and multivariate Cox proportional hazards regression models, and we developed a risk stratification model for prognostic prediction.Results:The median follow-up duration for the cohort of 132 patients was 54.2 months. During this period, 61 patients (46.2%) experienced recurrence or distant metastasis, resulting in a 5-year DFS rate of 54.1%. Additionally, 33 patients (25.0%) died, corresponding to a 5-year overall survival (OS) rate of 76.7%. Univariate Cox proportional hazards regression model analysis indicated that ten clinicopathological factors were significantly associated with OS (all P＜0.05). These factors include the total number of lymph nodes (LNs) dissected from the primary tumor (PT) <16, the number of negative LNs from the PT <13, pN(+) of the PT, logarithmic odds of positive lymph nodes (LODDS) of the PT ≥-1.1, lymph nodes ratio (LNR) of the PT ≥0.02, preoperative carcinoembryonic antigen (CEA) level before LMs resection ≥10 ng/ml, the presence of hilar/mediastinal LN metastasis, the number of LMs ≥2, the maximum diameter of LMs ≥2.5 cm, and the necessity for hilar/mediastinal lymphadenectomy. Multivariate Cox proportional hazards regression analysis identified the number of negative LNs <13 ( HR=3.01, 95% CI: 1.28-7.03, P=0.011), pN(+) of the PT ( HR=5.04, 95% CI: 1.51-16.84, P=0.009), preoperative CEA level before LMs resection ≥10 ng/ml ( HR=5.39, 95% CI: 1.80-16.19, P=0.003), the number of LMs ≥2 ( HR=2.47, 95% CI: 1.09-5.60, P=0.030), and the necessity for hilar/mediastinal lymphadenectomy ( HR=2.74, 95% CI: 1.15-6.52, P=0.023) as independent prognostic risk factors. Patients were categorized based on independent risk factors, revealing statistically significant differences in OS across the groups with CRS scores of ≤2, 3～4, and ≥5 ( P＜0.001). Conclusions:Independent risk factors associated with LMs from CRC patients include the number of negative LNs <13, pN(+) of the PT, preoperative CEA level before LMs resection ≥10 ng/ml, the number of LMs ≥2, and the necessity for hilar/mediastinal lymphadenectomy. Patients scoring 3 or higher on the CRS model may warrant cautious assessment for the appropriateness of direct surgical treatment.

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.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

To summarize the nursing experience of a patient with acute injection botulism complicated with respiratory failure.The key nursing points include early standard use of botulinum antitoxin therapy to improve the signs of myasthenia;to strengthen respiratory support and airway management,to carry out respiratory training,and to promote the recovery of respiratory function;swallowing function training and dynamic evaluation were carried out to promote the recovery of swallowing function;narrative nursing was carried out to relieve patient's negative emotions.After 17 days of treatment and nursing care,the patient was removed from the tracheal tube on the 7th day,transferred to the general ward on the 14th day,and discharged successfully on the 17th day with a good prognosis.A telephone follow-up was conducted 4 months after discharge,and the patient recovered well.