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*

ObjectiveTo explore the effect of grain-sized moxibustion at "Zhongwan （RN12）" "Tianshu （ST25）" and "Shangjuxu （ST37）" on the colon tissue of mice with ulcerative colitis （UC）， and to analyze the potential mechanism. MethodsForty C57BL/6 male mice were randomly divided into blank group， model group， moxibustion group and mesalazine group， with 10 mice in each group. In all the groups except for the blank group， UC mouse model was prepared by freely drinking 3% sodium dextran sulfate solution. After successful modeling， the moxibustion group was treated with grain-sized moxibustion at Zhongwan， Tianshu and Shangjuxu ， 3 cones per acupoint， 30 s of each cone. The mesalazine group was given 300 mg/kg of mesalazine enteric-coated tablet solution by gavage. The blank group and the model group were only fixed by grasping without any intervention. Each group was intervened once a day for 7 consecutive days. The general condition of mice in each group was observed， and the disease activity index （DAI） score was evaluated. The colon length， intestinal weight and colon mucosal injury score were detected. The contents of serum intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） were detected by ELISA. The pathological changes of colon tissue were observed by HE staining. The mRNA and protein expressions of non-receptor tyrosine protein kinase 2 （JAK2）， signal transducer and activator of transcription 3 （STAT3） and suppressor of cytokine signaling 3 （SOCS3） in colon tissue of mice were detected by real-time fluorescence quantitative PCR and immunohistochemistry， respectively. The mean fluorescence intensity of JAK2 and SOCS3 in colon tissue of mice was detected by immunofluorescence double staining. ResultsCompared to the blank group， the mice in the model group had unclean perianal area， unformed stool， destroyed colonic mucosal morphology， shortened body weight and colon length， increased DAI score， intestinal weight index， colonic mucosal injury and pathological score， serum ICAM-1， IL-6 and TNF-α levels， increased mRNA and protein expression of JAK2 and STAT3 in colon tissue， and decreased mRNA and protein expression of SOCS3 （P＜0.01）. Compared to those in the model group， the perianal area of mice in the moxibustion group and the mesalazine group was improved， and the colonic mucosal morphology was more complete； body weight and colon length increased， while DAI score， intestinal weight index， colonic mucosal injury and pathological score， serum ICAM-1， IL-6 and TNF-α levels decreased， with decreased mRNA and protein expression of JAK2 and STAT3 in colon tissue， and increased SOCS3 mRNA and protein expression （ P＜0.01 or P＜0.05 ）. There was no significant difference in any index between the moxibustion group and the mesalazine group. ConclusionGrain-sized moxibustion at "Zhongwan"， "Tianshu" and "Shangjuxu" can improve the damage of colon mucosa in UC model mice， and the mechanism may be related to the key factors regulating JAK2 / STAT3 signaling pathway based on SOCS3.

Since the concept of patient versions of guidelines （PVGs） was introduced into China， several PVGs have been published in China， but we found that there is a big difference between the concept of PVG at home and abroad， and the reason for this difference has not been reasonably explained， which has led to ambiguity and even misapplication of the PVG concept by guideline developers. By analyzing the background and purpose of PVGs， and the understanding of the PVG concept by domestic scholars， we proposed the term patient guidelines （PGs）. This refers to guidelines developed under the principles of evidence-based medicine， centered on health issues that concern patients， and based on the best available evidence， intended for patient use. Except for the general attribute of providing information or education， which is typical of common health education materials， PGs also provide recommendations and assist in decision-making， so PGs include both the patient versions of guidelines （PVG） as defined by the Guidelines International Network （GIN） and "patient-directed guidelines"， i.e. clinical practice guidelines resulting from the adaptation or reformulation of recommendations through clinical practice guidelines.

At present， the process and methodology of patient guidelines （PGs） development varies greatly and lacks systematic and standardised guidance. In addition to the interviews with PG developers， we have sorted out the relevant methodology for the adaptation and development of existing clinical practice guideline recommendations and facilitated expert deliberations to achieve a consensus， so as to finally put forward a proposal for guidance on the process and methodology for the development of PGs. The development of PGs can be divided into the preparation stage， the construction stage， and the completion stage in general， but the specific steps vary according to the different modes of development of PGs. The development process of Model 1 is basically the same as the patient version of the guideline development process provided by the International Guidelines Network， i.e.， team formation， screening of recommendations， guideline drafing， user testing and feedback， approval and dissemination. The developer should also first determine the need for and scope of translating the clinical practice guideline into a patient version during the preparation phase. Model 2 adds user experience and feedback to the conventional clinical practice guideline development process （forming a team， determining the scope of the PG， searching， evaluating and integrating evidence， forming recommendations， writing the guideline， and expert review）. Based on the different models， we sort out the process and methods of PG development and introduce the specific methods of PG development， including how to identify the clinical problem and how to form recommendations based on the existing clinical practice guidelines， with a view to providing reference for guideline developers and related researchers.