ObjectiveTo investigate the protective effect of Xielitang on dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group， a model group， a sulfasalazine group （0.6 g·kg^-1）， and low-， medium-， and high-dose Xielitang groups （1.67， 3.34， 6.68 g·kg^-1）. After treatment for 42 d， the colon length was recorded， and the disease activity index （DAI） score was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10）. Hematoxylin-eosin （HE） staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor （FXR）， small heterodimer partner （SHP）， liver receptor homolog-1 （LRH-1）， cholesterol 7α-hydroxylase （CYP7A1）， and fibroblast growth factor receptor 4 （FGFR4） in liver and FXR， sodium-dependent bile acid transporter （ASBT）， and fibroblast growth factor 15 （FGF15） in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover， ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group， the model group showed significantly decreased colon length， IL-10 content， α-diversity index， abundance of Firmicutes and Lactobacillus， and content of deoxycholic acid （DCA） and lithocholic acid （LCA） （P<0.01）， significantly increased DAI score， IL-6 and TNF-α content， abundance of Bacteroidetes， and the content of cholic acid （CA）， chenodeoxycholic acid （CDCA）， and taurocholic acid （TCA） （P<0.05， P<0.01）， significantly down-regulated protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. In addition， the structure of colonic mucosa was destroyed， and inflammatory cells infiltrated in the model group. Compared with the model group， Xielitang could significantly increase the colon length， IL-10 content， α-diversity index， the abundance of Firmicutes and Lactobacillus， and DCA and LCA content （P<0.05， P<0.01）， decrease DAI score， abundance of Bacteroidetes， and the content of IL-6， TNF-α， CA， CDCA， and TCA （P<0.01）， up-regulate the protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and down-regulate the protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis， regulating intestinal flora imbalance， and maintaining bile acid homeostasis.

Objective To explore the dietary nutrition status and nutritional intervention strategy of patients with Alzheimer’s disease (AD). Methods Among the 1 332 patients with AD diagnosed at Xijing Hospital from January 2021 to December 2023 were enrolled as the study subjects. The dietary intake data of patients were collected through questionnaire surveys and dietary reviews. During the study period, 30 patients did not complete the intervention due to withdrawal or loss of follow-up. Based on the actual number of people who completed the intervention, AD patients were randomly divided into intervention group (n=651, individualized nutritional intervention strategy) and control group (n=651, routine nutritional intervention), and both groups were intervened for 3 months. The cognitive function (MMSE score and MoCA score), nutritional status (MNA scale, NRS-2002 scale), and quality of life (GQOL-74) of the two groups of AD patients were compared to evaluate the effectiveness of the intervention strategies. Results A total of 1 332 questionnaires were distributed, and 1 302 valid questionnaires were finally recovered, with an effective recovery rate of 97.75% (1 302/1 332). The survey results showed that there were no statistical differences in baseline characteristics and dietary nutrition status between the two groups of AD patients before intervention (P>0.05). After nutritional intervention, the cognitive function, quality of life, and nutritional status of patients in the intervention group were significantly improved. The MMSE score, MoCA score, MNA score, and GQOL-74 score of the intervention group were significantly higher than those of the control group, while the NRS-2002 score was lower than that of the control group (P<0.05). Conclusion Nutritional intervention strategy has a significant effect on improving nutritional status, cognitive function, and quality of life of AD patients.

Objective: To explore differences in the factors influencing parents and teachers assessments of preschool children s mental health using the Strengths and Difficulties Questionnaire (SDQ), so as to provide reference for promoting children s mental health. Methods: A retrospective analysis was conducted on the SDQ survey data of 14 763 middle and senior kindergarten children in Nanshan District, Shenzhen, from March to June 2023. Chi square χ 2 tests were used to analyze differences in mental health assessments between parents and teachers. Multivariate Logistic regression was employed to examine the factors influencing parental assessments, and Kappa coefficients were used to evaluate the consistency between parent and teacher evaluations. Results: The positive rate of mental health problems reported by parents (7.2%) was significantly higher than that reported by teachers (6.2%) ( χ 2=254.27, P <0.01). Gender differences revealed that parents reported a lower positive rate for boys (7.9%) compared to teachers (8.5%), whereas for girls, the parental positive rate (6.4%) was higher than that reported by teachers (3.8%) ( χ 2=163.59, 81.26, all P <0.01). Age related differences showed that parental positive rates for 4, 5, and 6 year olds (8.5%, 7.4%, 5.8%) were consistently higher than teachers assessments (6.3%, 6.7%, 5.4%) ( χ 2=41.23, 157.53, 63.67, all P <0.05). Univariate analysis of parental assessments indicated higher positive rates among boys (7.9%), 4 year olds (8.5%), mothers aged 20-35 ( 6.6 %), mothers with high school education or below (9.8%), fathers aged 23-40 (6.4%), fathers with high school education or below (10.3%), and children exposed to secondhand smoke (7.9%) ( χ 2=23.56-235.24, all P <0.01). Multivariate Logistic regression identified lower parental education levels and exposure to secondhand smoke as significant risk factors for abnormal SDQ assessments by parents ( χ 2=2.05, 1.62, 3.15, all P <0.05). The Kappa coefficients for parent-teacher agreement across SDQ subscales and total difficulties ranged from 0.04 to 0.12 (all P <0.01). Conclusions Parental education level and exposure to secondhand smoke are significant factors influencing preschool children s mental health. Differences exist between parental and teacher assessments of children s mental health, and incorporating teacher evaluations can provide a more comprehensive understanding of preschoolers psychological well being.

Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

Lung cancer stands as the primary cause of cancer-related mortalities globally, presenting a severe menace to human health. In individuals with non-small cell lung cancer (NSCLC), Kirsten rat sarcoma viral oncogene (KRAS) mutations serve as crucial oncogenic drivers. NSCLC with KRASG12C mutation is among the most prevalent subtypes. Currently, the detection methods for KRAS mutations predominantly concentrate on polymerase chain reaction (PCR) and sequencing platforms. The diverse derivative technologies of these two platforms each exhibit distinct merits and demerits in terms of testing performance and detection throughput, and find significant applications in tissue biopsy and liquid biopsy. In targeted therapies, KRASG12C targeted drugs, including Sotorasib, Adagrasib, Fulzerasib, Garsorasib, and Glecirasib, have demonstrated certain therapeutic efficacies in clinical trials and have obtained marketing approval. To tackle drug resistance and enhance patient's prognoses, combination therapeutic strategies that integrate targeted agents with chemotherapy, immune checkpoint inhibitors, Src homology region 2 domain-containing phosphatase 2 (SHP2) inhibitors, and epidermal growth factor receptor (EGFR) monoclonal antibodies have emerged. This paper systematically reviews the advancements in the diagnosis and targeted therapy of NSCLC with KRASG12C mutation, aiming to offer a reference for the selection of clinical treatment regimens and subsequent research.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Mutation ; Molecular Targeted Therapy

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To develop the Self-Stigma Scale for Drug Addicts(SSSDA),and test its validity and reliability.Methods:On the basis of literature analysis,open questionnaire survey,semi-structured interview and ex-pert consultation,the theoretical structure of the questionnaire was developed,and 943 drug addicts were test-ed.Sample 1(n=483)was used for item analysis and exploratory factor analysis,and sample 2(n=460)was used for confirmatory factor analysis,criterion related validity and internal consistency reliability analysis.Sixty-four drug addicts were retested 4 weeks later for test-retest reliability test.The criterion related validity was tested with the Drug Stereotype Threat Scale.Results:The scale consisted of 6 dimensions and 31 items,including self-negative cognition,stereotype identity,confidentiality,social avoidance,stigma experience,and stigma experience in the process of detoxification(factor loadings were from 0.41 to 0.81),which explained 64.09％of the total vari-ance.The 6-factor structure model fitted the data well(x2/df=2.82,RMSEA=0.06,CFI=0.92,GFI=0.85,TLI=0.91).The total scores and factor scores of the SSSDA were positively correlated with the DSTS scores(ICC=0.10-0.22,Ps＜0.05).The Cronbach α coefficients for the total scale and each dimension were between 0.80 and 0.95,and the test-retest reliability coefficients(ICC)were between 0.82 and 0.94.Conclusion:The Self-stigma Scale for Drug Addicts(SSSDA)initially developed in this study has satisfactory reliability and validity.

Objective:To evaluate the efficacy of radiotherapy/chemotherapy combined with immune checkpoint inhibitors (ICIs) in patients with locally recurrent or metastatic esophageal squamous cell carcinoma (LR/M ESCC) after first-line radical treatment.Methods:A retrospective analysis was conducted on 116 enrolled patients with LR/M ESCC. Factors influencing patient prognosis were analyzed, and a stratified analysis was performed focusing on inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) before second-line treatment, the intervention timing and extent of radiotherapy, and treatment efficacy. Additionally, treatment-related adverse effects with grade ≥2 and failure patterns of the patients after second-line treatment were examined.Results:After second-line treatment, the median OS and PFS were 19.4 and 12.0 months, respectively, and the overall objective response rate and disease control rate were 38.8% and 86.2%, respectively. Patients with lower NLR and PLR values exhibited significantly higher OS ( χ2 = 14.93, 11.60, P < 0.05) and PFS rates ( χ2=17.55, 8.95, P<0.05) compared to those with higher NLR and PLR values. Radiotherapy significantly improved the OS rates ( χ2 = 5.93, P < 0.05) of the patients, but produced insignificant effects on their PFS rates ( P > 0.05). Patients receiving whole-field radiotherapy exhibited superior OS and PFS rates compared to those treated with partial-field radiotherapy ( χ2 = 8.88, 4.93, P < 0.05). The intervention time of radiotherapy had no significant effects on the OS and PFS of the patients ( P > 0.05). The prognosis of the CR+ PR group was significantly better than that of the SD+ PD group ( χ2 = 8.97, 10.67, P > 0.05). The Cox multivariate analysis result identified the recurrence type, PLR, the number of immunotherapy cycles, local radiotherapy intervention, and recent efficacy as independent risk factors in the patients′OS ( HR = 2.67, 4.63, 0.39, 2.10, 3.35, P<0.05) and determined that NLR, PLR, the number of immunotherapy cycles, and recent efficacy were independent risk factors affecting the patients′ PFS ( HR = 1.79, 1.88, 0.54, 2.50, P<0.05). Among the patients, 38 (32.8%) experienced disease progression after second-line treatment, and 36 (31.0%) suffered from treatment-related adverse effects of grades ≥2, which were generally tolerable. Conclusions:Second-line treatment with ICIs combined with radiotherapy/chemotherapy can improve the prognosis of patients with LR/M ESCC. Further clinical exploration is warranted regarding the intervention timing and extent of radiotherapy.

This study performed to determine whether OX40L overexpressed by recombinant rabies virus(LBNSE-OX40L)can enhance the innate immune response through activation of dendritic cells and thus activate early antibody production.Bone marrow dendritic cells(BMDCs)were extracted from the femur of Balb/c mice and cultured for 6 days,and the cultured BMDCs were infected with the parental virus LBNSE and the recombinant virus LBNSE-OX40L with the multiplicity of infections(MOI)=1.The effect of each virus on the maturation of BMDCs was analyzed by flow cytometry;ELISA was used to detect the expression of innate immunity-related cytokines such as interferon-α(IFN-α)and interleukin-12p40(IL-12p40)in the supernatants of the infected BMDCs.For in vivo study,Balb/c female mice were injected intramuscularly with 106 FFU of parental virus LBNSE and recombinant virus LBNSE-OX40L in both hind limbs,and the inguinal lymph nodes of mice were collected on day 6 after immunization,and the proportion of mature DCs was detected by flow cytometry.The serum was collected on day 6 after immunization,and the content of virus-neutralizing antibody(VNA)was detected by antiviral neutralizing antibody titration.Mouse serum was collected on day 6 after immunization,and virus neutralizing antibody content was measured by titration of antiviral neutralizing antibody,while IgG antibody in mouse serum was detected by ELISA.IgM antibody subclasses were detected by ELISA on days 2,4,and 6 after immunization.Compared with the parental virus LBNSE,the recombinant virus LBNSE-OX40L was able to activate more BMDCs in vitro and produce significantly higher levels of IFN-α and IL-12p40.Furthermore,the recombinant virus LBNSE-OX40L stimulated the maturation and differentiation of the DCs in vivo,which led to the rapid production of high levels of VNA and RABV-specific IgG and IgM antibodies.Taken together,LBNSE-OX40L activates dendritic cells to promote the body's innate immune response,and in turn enhances early antibody production,thus can be an early effective rabies vaccine candidate.