ObjectiveTo explore the potential mechanism of Xiezhuo Jiedu prescription in regulating autophagy in the treatment of ulcerative colitis （UC） by bioinformatics and animal experiments. MethodsThe differentially expressed genes （DEGs） in the colonic mucosal tissue of UC patients was obtained from the Gene Expression Omnibus （GEO）， and those overlapped with autophagy genes were obtained as the differentially expressed autophagy-related genes （DEARGs）. DEARGs were imported into Metascape and STRING， respectively， for gene ontology/Kyoto Encyclopedia of Genes and Genomics （GO/KEGG） enrichment analysis and protein-protein interaction （PPI） analysis. Finally， 15 key DEARGs were obtained. The core DEARGs were obtained by least absolute shrinkage and selection operator （LASSO） regression and receiver operating characteristic curve （ROC） analysis. The CIBERSORT deconvolution algorithm was used to analyze the immunoinfiltration of UC patients and the correlations between core DEARGs and immune cells. C57BL/6J mice were assigned into a normal group and a modeling group. The mouse model of UC was established by free drinking of 2.5% dextran sulfate sodium. The modeled mice were assigned into low-， medium-， and high-dose Xiezhuo Jiedu prescription and mesalazine groups according to the random number table method and administrated with corresponding agents by gavage for 7 days. The colonic mucosal morphology was observed by hematoxylin-eosin staining. The protein and mRNA levels of cysteinyl aspartate-specific proteinase 1 （Caspase-1）， cathepsin B （CTSB）， C-C motif chemokine-2 （CCL2）， CXC motif receptor 4 （CXCR4）， and hypoxia-inducing factor-1α （HIF-1α） in the colon tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultsThe dataset GSE87466 was screened from GEO and interlaced with autophagy genes. After PPI analysis， LASSO regression， and ROC analysis， the core DEARGs （Caspase-1， CCL2， CTSB， and CXCR4） were obtained. The results of immunoinfiltration analysis showed that the counts of NK cells， M0 macrophages， M1 macrophages， and dendritic cells in the colonic mucosal tissue of UC patients had significant differences， and core DEARGs had significant correlations with these immune cells. This result， combined with the prediction results of network pharmacology， suggested that the HIF-1α signaling pathway may play a key role in the regulation of UC by Xiezhuo Jiedu prescription. The animal experiments showed that Xiezhuo Jiedu prescription significantly alleviated colonic mucosal inflammation in UC mice. Compared with the normal group， the model group showed up-regulated protein and mRNA levels of caspase-1， CCL2， CTSB， CXCR4， and HIF-1α， which were down-regulated after treatment with Xiezhuo Jiedu prescription or mesalazine. ConclusionCaspase-1， CCL2， CTSB， and CXCR4 are autophagy genes that are closely related to the onset of UC. Xiezhuo Jiedu prescription can down-regulate the expression of core autophagy genes to alleviate the inflammation in the colonic mucosa of mice.

Objective: To investigate the implementation and evaluate the effectiveness of health management services for patients with type 2 diabetes mellitus (T2DM) in Urumqi City from 2017 to 2021, so as to provide the reference for enhancing T2DM patients management. Methods: Data on the rates of record establishment, health management and standardized management for T2DM patients, and blood glucose control rate in managed patients in Urumqi City from 2017 to 2021 were collected through the quarterly reports on basic public health service management from the Weining Health Platform System. The trends in the four management indicators, and the differences between urban and rural areas were analyzed. Results: The rates of record establishment, health management and blood glucose control rate in managed patients in Urumqi City were 46.94%, 38.37% and 59.92%, respectively, showing upward trends from 2017 to 2021 (all P<0.05). The rate of standardized management was 75.89%, showing a downward trend (P<0.05). The rate of record establishment was higher in urban areas than in rural areas (47.76% vs. 40.56%, P<0.05). The rates of standardized management and blood glucose control in managed patients were lower in urban areas than in rural areas (75.18% vs. 81.46%, 58.93% vs. 67.64%, both P<0.05). The rate of health management was 38.39% in urban areas and 38.24% in rural areas, with no statistically significant difference (P>0.05). The trends in the rates of record establishment, health management and standardized management in both urban and rural areas were consistent with those in the overall population. Conclusions From 2017 to 2021, the rates of record establishment, health management and blood glucose control in managed patients in Urumqi City showed upward trends, while the rate of standardized management exhibited a downward trend. There were urban-rural differences in the rates of record establishment, standardized management and blood glucose control in managed patients.

ObjectiveTo investigate the association and translational mechanism between the hepatotoxicity of Xianling Gubao （XLGB） and its treatment of osteoporosis based on a zebrafish model. MethodsZebrafish were randomly selected four days after fertilization （4 dpf） and exposed to different concentrations of XLGB （0.7，0.35 mg·L^-1） for 96 h. At the endpoint of the exposure， the mortality rates of zebrafish in the treatment groups of different concentrations were counted， and the "dose-toxicity" curves were plotted. The 10% sublethal concentration （LC₁₀） was calculated. The liver area， acridine orange staining， and pathological tissue sections of transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP）］ were used as indicators to confirm the hepatic damage caused by the sublethal concentration of XLGB. By using the prednisolone （PNSL）-induced osteoporosis model of zebrafish， the anti-osteoporosis activity of XLGB was evaluated by using the area of skull stained by alizarin red and the cumulative optical density value as indicators. Then， the toxicity difference of XLGB on the liver of zebrafish in healthy and osteoporotic states was compared， and the mechanism of the translational action of the toxicity of XLGB was predicted based on network pharmacology and real-time polymerase chain reaction（Real-time PCR）. ResultsThe LC₁₀ of XLGB on zebrafish （8 dpf） was 0.7 mg·L^-1. Compared with the blank group， the sublethal concentration （LC₁₀=0.7 mg·L^-1， 1/2 LC₁₀=0.35 mg·L^-1） of XLGB induced an increase in the number of apoptosis of hepatocytes in a dose-dependent manner， and the tissue arrangement of the liver was disordered and loose. The vacuoles were obvious， and the fluorescence area of the liver was significantly reduced （P<0.01）. Compared with the blank group， the mineralized area and cumulative optical density value of zebrafish skull in the PNSL model group were significantly reduced （P<0.01）， and those in the 0.7，0.35 mg·L^-1 XLGB treatment group were significantly increased compared with the model group （P<0.01）. Most importantly， 0.7 mg·L^-1 XLGB had no significant effect on the liver of zebrafish in the osteoporosis disease model compared with the blank group. The results of network pharmacology and real-time PCR experiments showed that the toxic transformation of XLGB might be related to the differences in the expression levels of key targets， such as tumor protein 53 （TP53）， cysteine aspartic acid specific protease-3（Caspase-3）， interleukin（IL）-6， and alkaline phosphatase（ALP） in different organismal states. ConclusionUnder certain conditions， XLGB has hepatotoxicity in normal zebrafish， but under osteoporotic conditions， XLGB not only exerts significant anti-osteoporosis activity but also alleviates hepatotoxicity significantly， which provides a reference for the safe clinical use of XLGB and real evidence for the theories of traditional Chinese medicine of attacking poison with poison and of treating disease with corresponding drugs without damage to the body.

AIM: To investigate the alterations in corneal aberration and relative refractive power following the reduction of back optic zone diameters(BOZD)of orthokeratology lenses.METHODS: Myopic children aged 8-12 years, deemed suitable and willing to wear orthokeratology lenses, were randomly allocated to wear lenses with a 6.0 mm BOZD or a 5.0 mm BOZD. Data collection included changes in higher-order aberrations, relative refractive power and the treatment zone diameter of the two groups after wearing lenses for 1 d, 1 wk, 1, and 3 mo. The correlation of increase in corneal higher-order aberrations with refractive power was analyzed.RESULTS: The increases in total higher-order aberrations, spherical aberrations and coma aberrations varied over time following lens wear(all P<0.001), and there were no statistically significant differences in the changes of total higher-order aberrations and coma aberrations between the two groups of patients(all P>0.05). A significant difference was observed in the increment of spherical aberrations in the 5 mm range between the two groups of patients, which varied over time(Ftime=40.179, Ptime<0.001; Fgroup=11.948, Pgroup=0.001; Finteraction=3.262, Pinteraction=0.03). A significant difference was observed in the increment of spherical aberrations in the 4 mm range between the two patient groups(Ftime=34.462, Ptime<0.001; Fgroup=13.094, Pgroup<0.001; Finteraction=1.372, Pinteraction=0.25). There was no statistically significant distinction in relative refractive power between the two groups(Fgroup=0.048, Pgroup=0.83; Finteraction=1.208, Pinteraction=0.31); however, relative refractive power changed over time(Ftime=40.030, Ptime<0.001). The difference in treatment zone diameter between the two groups was statistically significant, with changes over time(Ftime=11.212, Ptime<0.001; Fgroup=74.073, Pgroup<0.001; Finteraction=0.312, Pinteraction=0.82). The total higher-order aberrations, spherical aberrations, and coma aberrations in 4, 5 and 6 mm range showed a positive correlation with relative refractive power values(all P<0.001). Statistically significant difference was observed in the axial length between the two groups after wearing lenses for 3, 6 and 12 mo(Ftime=185.398, Ptime<0.001; Fgroup=5.618, Pgroup=0.02; Finteraction=2.315, Pinteraction=0.11).CONCLUSION: Orthokeratology lenses leaded to elevated higher-order aberrations. Orthokeratology lenses with smaller BOZD produced significantly greater spherical aberrations at 4 and 5 mm range and smaller treatment zone diameters. The corneal total higher-order aberration was positively correlated with relative refractive power. Wearing orthokeratology lenses with a smaller BOZD can cause slower axial growth and better myopia control.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

OBJECTIVE To observe the effects of Modified shaoyao gancao decoction on intestinal transit function， intestinal flora and the contents of metabolites [γ aminobutyric acid （GABA） and 5-hydroxytryptamine （5-HT）] in slow transit constipation （STC） rats. METHODS SD rats were randomly divided into blank group （10 rats） and modeling group （30 rats）， with half male and half female. The STC model was established by intragastric administration of Compound diphenoxylate tablets in the modeling group. The successfully modeled rats were randomly divided into model group， Modified shaoyao gancao decoction group [56 g/（kg·d）， calculated by crude drug] and positive control group [lactulose 2.09 g/（kg·d）]， with 10 rats in each group. Each administration group was given relevant medicine intragastrically， the blank group and model group received an equivalent volume of normal saline， once a day， for 14 consecutive days. During the experiment， the general situation of rats was observed in each group. After the last medication， the body weight was measured， and the Bristol score was used to evaluate the fecal characteristics. The fecal moisture content， intestinal propulsion rate， and the contents of GABA and 5-HT in intestinal content were detected； the diversity of intestinal flora in intestinal contents was investigated， and the correlation between the contents of GABA， 5-HT and relative abundance of microbiota was analyzed. RESULTS Compared with the model group， general conditions such as small body shape， sparse and rough fur， and slow movement were all improved in Modified shaoyao gancao decoction body weight， Bristol score， fecal moisture content，intestinal propulsion rate， 5-HT content， Chao1 index and Shannon index were increased significantly， while GABA content and Simpson index were decreased significantly （P＜0.05）. The intestinal flora of rats in the Modified shaoyao gancao decoction group could be classified as the same as the blank group， but was far from the model group； the relative abundances of Desulfobacterota， Firmicutes and Bacteroidota in this group showed a tendency of pull back， but the differences were not statistically significant compared to model group （P＞0.05）. Desulfobacterota was an intergroup differential factor （P＜0.05）. The content of GABA was negatively correlated with the relative abundance of Bacteroidota， Cyanobacteria， Patescibacteria and Actinobacteriota （P＜0.05）. The content of 5-HT was positively correlated with the relative abundance of Campilobacterota （P＜0.05）. CONCLUSIONS Modified shaoyao gancao decoction can improve the fecal properties and intestinal motility of STC rats. Its mechanism may be related to improving intestinal flora and then affecting the contents of GABA and 5-HT in intestinal contents. In addition， the contents of GABA and 5-HT may be significantly correlated with the relative abundance of specific bacterial phyla such as Bacteroidota and Campilobacterota.

OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

OBJECTIVE To observe the effects of Modified shaoyao gancao decoction on intestinal transit function， intestinal flora and the contents of metabolites [γ aminobutyric acid （GABA） and 5-hydroxytryptamine （5-HT）] in slow transit constipation （STC） rats. METHODS SD rats were randomly divided into blank group （10 rats） and modeling group （30 rats）， with half male and half female. The STC model was established by intragastric administration of Compound diphenoxylate tablets in the modeling group. The successfully modeled rats were randomly divided into model group， Modified shaoyao gancao decoction group [56 g/（kg·d）， calculated by crude drug] and positive control group [lactulose 2.09 g/（kg·d）]， with 10 rats in each group. Each administration group was given relevant medicine intragastrically， the blank group and model group received an equivalent volume of normal saline， once a day， for 14 consecutive days. During the experiment， the general situation of rats was observed in each group. After the last medication， the body weight was measured， and the Bristol score was used to evaluate the fecal characteristics. The fecal moisture content， intestinal propulsion rate， and the contents of GABA and 5-HT in intestinal content were detected； the diversity of intestinal flora in intestinal contents was investigated， and the correlation between the contents of GABA， 5-HT and relative abundance of microbiota was analyzed. RESULTS Compared with the model group， general conditions such as small body shape， sparse and rough fur， and slow movement were all improved in Modified shaoyao gancao decoction body weight， Bristol score， fecal moisture content，intestinal propulsion rate， 5-HT content， Chao1 index and Shannon index were increased significantly， while GABA content and Simpson index were decreased significantly （P＜0.05）. The intestinal flora of rats in the Modified shaoyao gancao decoction group could be classified as the same as the blank group， but was far from the model group； the relative abundances of Desulfobacterota， Firmicutes and Bacteroidota in this group showed a tendency of pull back， but the differences were not statistically significant compared to model group （P＞0.05）. Desulfobacterota was an intergroup differential factor （P＜0.05）. The content of GABA was negatively correlated with the relative abundance of Bacteroidota， Cyanobacteria， Patescibacteria and Actinobacteriota （P＜0.05）. The content of 5-HT was positively correlated with the relative abundance of Campilobacterota （P＜0.05）. CONCLUSIONS Modified shaoyao gancao decoction can improve the fecal properties and intestinal motility of STC rats. Its mechanism may be related to improving intestinal flora and then affecting the contents of GABA and 5-HT in intestinal contents. In addition， the contents of GABA and 5-HT may be significantly correlated with the relative abundance of specific bacterial phyla such as Bacteroidota and Campilobacterota.

Objective To understand the situation of corn mycotoxins contamination in Heilongjiang Province , and to analyze the causes of pollution and propose prevention and control measures. Methods Among the 473 corn samples were collected from various regions in Heilongjiang Province , and 16 mycotoxins , including aflatoxins , fumonisins, deoxynivalenol and their metabolites , zearalenone , ochratoxin A , alternariol , alternariol monomethyl ether , tentoxin , and tenuazonic acid , were detected in the corn samples. The detection and quantification were carried out using ultra-high performance liquid chromatography tandem mass spectrometry isotope internal standard method. Results All samples were detected with mycotoxins, the detection rate was 100%, and each sample was contaminated by one or more mycotoxins. The detection rate of 16 mycotoxins ranged from 0.21% to 98.31%. The average contamination level ranged from 0.67 μ g/kg-259.19 μ g/kg. Three types of toxins exceeded the standard, with exceeding rates of deoxynivalenol (2.54%, 12/473), zearalenone (4.02% ,19/473), and fumonisins (2.54%,12/473), respectively. The samples exceeding the standard were distributed in Mudanjiang, Shuangyashan, Jixi, Harbin, and Qiqihar. Conclusion Corn in Heilongjiang Province is contaminated by a combination of mycotoxins. It is necessary to strengthen monitoring from multiple links and adopt a variety of ways and control measures to reduce corn contamination.