ObjectiveTo observe the effects of Dihuang Yinzi （DY） on motor dysfunction in rats with advanced Parkinson's disease （PD） and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids （SCFAs）-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group， model group， positive drug group （levodopa， 50 mg·kg^-1）， and DY low-， medium-， and high-dose groups （5.2， 10.4， 20.8 g·kg^-1）. After 7 days of administration， motor function was evaluated using the open-field， pole-climbing， and inclined plate tests. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the substantia nigra and colon， and immunohistochemistry was performed to detect α-Synuclein （α-Syn） and tyrosine hydroxylase （TH） expression in the substantia nigra. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of dopamine （DA）， 5-hydroxytryptamine （5-HT）， 3，4-dihydroxyphenylacetic acid （DOPAC）， Levodopa， homovanillic acid （HVA）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）. Western blot analysis was used to detect the expression of zonula occludens-1 （ZO-1） and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing， and gas chromatography （GC） was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group， the model group showed significantly decreased movement speed and distance in the open-field test， prolonged pole-climbing time， and reduced retention angle on the inclined plate （P<0.01）， accompanied by increased α-Syn expression （P<0.01） and decreased TH expression （P<0.01） in the brain. Compared with the model group， all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees （P<0.05， P<0.01） and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra （P<0.01） and increased TH expression （P<0.01）. ELISA and Western blot results showed that， compared with the normal group， the model group exhibited decreased levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum （P<0.01）， increased levels of TNF-α， IL-6， and IL-1β in the colon and striatum （P<0.01）， and significantly reduced expression of ZO-1 （P<0.05） and occludin in the colon （P<0.01）. Compared with the model group， all DY dose groups increased the levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum to varying degrees （P<0.05， P<0.01）. In the high-dose DY group， the levels of TNF-α， IL-6， and IL-1β in the colon and striatum were reduced （P<0.01）， while the expression of ZO-1 （P<0.05） and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota， Enterobacteriaceae， and Erysipelotrichaceae were increased in the model group， whereas the relative abundances of Bacteroidota， class Clostridia， Lachnospiraceae， and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased （P<0.05， P<0.01）， while after high-dose DY intervention， the levels of acetate， propionate， isobutyrate， and butyrate were significantly increased （P<0.05， P<0.01）. ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.

Objective: To explore the prevalence of bone defect and alveolar bone thickness changes in the mandibular incisors of untreated adults and post-orthodontic treatment adults, with the aim of providing strategies for preventing and managing alveolar bone defects during orthodontic treatment. Methods: This study was reviewed and approved by the Medical Ethics Committee. Clinical records, panoramic radiographs, cephalometric radiographs, and cone beam computed tomography (CBCT) images and informed consent were obtained for 150 untreated adults and 150 post-orthodontic adults. The untreated adults and post-orthodontic adults were respectively divided into three subgroups: skeletal ClassⅠ, Class Ⅱ and Class Ⅲ, with 50 cases per subgroup. Meanwhile, 60 cases with completeness of pre- and post-orthodontic data were enrolled from 150 post-orthodontic adults, including 20 cases each of skeletal ClassⅠ, Class Ⅱ, and Class Ⅲ. Cephalometric radiographs were imported into Dolphin software to measure skeletal parameters. CBCT images were imported into Mimics software to assess alveolar bone defects and to measure alveolar bone thickness of mandibular incisors among three groups: 150 untreated adult groups, 150 post-orthodontic groups and the pre- and post-treatment status of 60 patients selected from the latter group. Results: Untreated adult patients: the prevalence of labial dehiscence and fenestration in the mandibular incisors was higher than that on the lingual side among skeletal ClassⅠ, Ⅱ, and Ⅲ malocclusion patients, and there was a statistically significant difference in the alveolar bone thickness of the mandibular incisors among the three classes. Post-orthodontic treatment adults: for skeletal ClassⅠ and Ⅱ patients, the prevalence of lingual bone dehiscence in the mandibular incisors was significantly higher in the extraction groups than in the non-extraction groups; correspondingly, the lingual alveolar bone was also thinner in the extraction groups; Class Ⅱ non-extraction patients showed a higher prevalence of labial bone fenestration but a lower prevalence of lingual bone fenestration in mandibular incisors compared to Class Ⅱ extraction patients; the orthodontic-orthognathic combined treatment group showed significantly higher prevalence of labial/lingual bone dehiscence and thinner alveolar bone at multiple sites in the mandibular incisors compared to the camouflage group in skeletal Class Ⅲ patients. Comparison of mandibular incisor bone defects and thickness before and after orthodontic treatment in adult patients: in skeletal ClassⅠ and Ⅱ patients treated with premolar extraction and Class Ⅲ patients treated with orthodontic-orthognathic combined treatment, the lingual alveolar bone of mandibular incisors exhibited significant resorption and thinned after treatment, and this was accompanied by an increased prevalence of dehiscence; in non-extraction patients, ClassⅠ non-extraction patients showed thinning of the crestal-labial bone and apical-lingual bone, Class Ⅱ patients showed thinning of the crestal-labial bone and middle-labial bone of the mandibular incisors, along with an increased prevalence of dehiscence Conclusion In malocclusion adults, alveolar bone defects were already present in the mandibular incisors before orthodontic treatment. The alveolar bone defects and thickness in mandibular incisors among post-orthodontic adults were influenced by the treatment plan and Class of skeletal malocclusion.

The incidence rate of hepatic fibrosis remains at a high level， and there is still a lack of specific therapeutic drugs， posing a serious threat to human health. As a type of natural active components widely present in plants， flavonoids have multiple physiological functions such as antioxidant， anti-inflammatory， and anti-fibrotic activities， and a large number of studies have confirmed the anti-hepatic fibrosis effect of flavonoids. As for the mechanism of action， flavonoids can target the functions of hepatic stellate cells by inhibiting their proliferation and differentiation， promoting their apoptosis， regulating the level of autophagy， reducing the formation of extracellular matrix， and regulating iron metabolism in hepatic stellate cells， and meanwhile， they can inhibit chronic liver inflammatory response， improve oxidative stress status， regulate intestinal flora balance， and block epithelial-mesenchymal transition， thereby blocking the progression of fibrosis through multiple dimensions. At the level of signaling pathways， flavonoids mainly exert an anti-fibrotic effect by regulating the abnormal activation of the signaling pathways such as transforming growth factor-β1/Smad， Janus kinase/signal transducer and activator of transcription， nuclear factor erythroid 2-related factor 2， nuclear factor-kappa B， phosphatidylinositol 3-kinase/protein kinase B， mitogen-activated protein kinase， Wnt/β-catenin， and adenosine 5'-monophosphate-activated protein kinase. This article summarizes the research advances in the anti-fibrotic effect of flavonoids， in order to provide a theoretical basis for further exploring their medicinal potential.

Nanocarrier-based drug delivery systems can provide new research strategies for targeted intervention at atherosclerosis （AS） lesions by regulating the in vivo distribution and release behavior of drugs. Existing studies have shown that polymeric and lipid nanocarriers， cell membrane-coated systems， and microenvironment-responsive drug delivery strategies can intervene in the pathological progression of AS by modulating macrophage function， promoting cholesterol efflux， and controlling inflammation and oxidative stress； some systems have attempted to achieve multi-target synergistic intervention through combined delivery and theranostics； some drug delivery systems can improve drug enrichment in lesions and modulate related pathological processes. However， their long-term safety， lesion-targeting stability， scale-up manufacturing， and incremental clinical benefit remain to be validated. In the future， it is necessary to strengthen the matching between delivery mechanisms and pathological features and to establish evaluation systems for pharmacokinetics and safety， thereby providing a basis for the clinical translation of nanocarrier-based drug delivery systems.

ObjectiveTo explore the mechanism of Huashi Baidu granules in treating influenza A （H1N1） virus infection based on the gut-lung axis. MethodsBALB/c mice were randomly assigned into a blank control group， a model control group， a positive control （oseltamivir phosphate capsules， 19.5 mg·kg^-1） group， and a Huashi Baidu granules （17.81 g·kg^-1） group. Mice in other groups except the blank control group were instilled nasally by H1N1 viral fluid for the modeling of influenza viral pneumonia and treated with corresponding drugs once daily by gavage for 5 consecutive days. The mouse lung index was calculated， and pathological changes in the lung and colon tissue were observed. Western blot was employed to quantify the expression levels of nucleotide-binding oligomeric domain-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific proteinase -1 （Caspase-1）， apoptosis-associated Speck-like protein containing a CARD （ASC）， gasdermin D （GSDMD）， interleukin-18 （IL-18）， IL-1β， and colonic tight junction protein 1 （CLDN1）， and Occludin in the lung and colon tissue. Non-targeted metabolomics was employed to analyze the metabolic profiles of the lung tissue and intestinal contents. The 16S rRNA sequencing was performed to analyze the gut microbiota structure in intestinal contents. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the 5-hydroxytryptamine （5-HT） levels in the serum， lung tissue， and colon tissue. ResultsCompared with the blank control group， the model control group showed elevated lung index， marked inflammatory cell infiltration and alveolar structural destruction in the lung tissue， obvious inflammatory cell infiltration and mucosal epithelial damage in the colon tissue， upregulated protein levels of NLRP3 inflammasome pathway proteins NLRP3， Caspase-1， GSDMD， IL-1β， and IL-18 in the lung and colon tissue （P<0.05， P<0.01）， downregulated protein levels of CLDN1 and Occludin in the colon tissue （P<0.05， P<0.01）. Compared with the model control group， Huashi Baidu Granules reduced the lung index （P<0.01）， alleviated pathological damage in the lungs and colon， inhibited the expression of NLRP3， Caspase-1， GSDMD， IL-1β， and IL-18 in lung and colon tissue （P<0.05， P<0.01）， and upregulated the expression of CLDN1 and Occludin in the colon tissue （P<0.05， P<0.01）. Metabolomics analysis showed that Huashi Baidu Granules downregulated the 5-HT pathway and arachidonic acid metabolism pathway in the lung and colon tissue， while upregulating nucleotide metabolism and TCA cycle. Compared with the blank control group， the model control group exhibited elevated levels of 5-HT in the serum， lung tissue， and colon tissue （P<0.01）. The intervention with Huashi Baidu Granules lowered the levels of 5-HT in the serum （P<0.05） and the lung and colon tissue （P<0.01）. Huashi Baidu Granules increased the diversity of gut microbiota， enriched beneficial bacteria such as Blautia， and inhibited pathogenic bacteria such as Desulfovibrio. ConclusionHuashi Baidu Granules significantly alleviate lung inflammation and pathological damage in mice infected with influenza A （H1N1） virus， reshape the intestinal microecology， and repair the intestinal barrier. It may exert cross-organ regulation by inhibiting the cascade of "gutogenic 5-HT release-circulatory transport-pulmonary 5-HT receptor activation-NLRP3 inflammasome assembly." It exerts therapeutic effects on influenza viral pneumonia through the gut-lung axis. This study provides a modern biological interpretation for the TCM theories of interior-exterior relationship between the lung and large intestine and simultaneous treatment of the lung and intestine.

OBJECTIVE To establish drug utilization evaluation （DUE） criteria for pyrotinib to promote its appropriate application in clinical practice. METHODS Based on the label of Pyrotinib maleate tablets， with relevant guiding principles and diagnostic and treatment guidelines as the evaluation basis， DUE criteria for pyrotinib were determined through the Delphi method. Attribute hierarchical model （AHM） and entropy weight method （EWM） were used to combine and assign weights to each indicator within the DUE criteria. Additionally， the weighted technique for order preference by similarity to an ideal solution （TOPSIS） method was applied to perform rationality evaluation of medication in archived medical records from Hainan Provincial Tumor Hospital and Hainan Western Central Hospital regarding the use of pyrotinib from November 2019 to November 2023. RESULTS The established DUE criteria for pyrotinib included 4 primary indicators （prescription authority， indications for use， medication process， and medication outcomes） and 11 secondary indicators. The secondary indicators with higher weights were the route of administration and dosage （0.257） and indications in the label （0.241）. Among the 88 archived cases included， there were 28 cases of inappropriate medication （31.82%）， 43 cases of generally appropriate medication （48.86%）， and 17 cases of appropriate medication （19.32%）. The main issues related to inappropriate medication involved off-label use （42.05%） and inappropriate routes of administration and dosage （43.18%）. CONCLUSIONS DUE criteria for pyrotinib established using the AHM-EWM-weighted TOPSIS method is highly operational and results in quantifiable evaluation outcomes. The overall rationality of the use of pyrotinib in the above hospitals remains to be improved， and there are some issues， like the off-label use，and inappropriate routes of administration and dosage being liaoyylyy@163.com unreasonable.

Recently, there has been an increasing risk of importation of tropical diseases into China and the resultant re-transmission in the country with the in-depth implementation of the “Belt and Road” Initiative, which poses a serious threat to the national public health security. To effectively respond to the cross-border transmission risk of tropical diseases and facilitate the process towards tropical disease control and elimination in China and the countries along the “Belt and Road” Initiative, this article analyzes the current status and governance risks of major imported tropical diseases, cross-border joint prevention and control polices implemented for tropical diseases and challenges in the establishment of the joint prevention and control system for tropical diseases in China, and discusses the establishment and implementation path of the joint prevention and control system for tropical diseases in countries along the “Belt and Road” Initiative. This path covers the establishment of cross-border cooperation mechanisms, research and development and pilot production of Chinese public health products, and implementation of key cross-border tropical disease prevention and control projects. The establishment of this system will further improve Chinese prevention and control capabilities for key cross-border tropical diseases, build a demonstrative prevention and control model for tropical diseases, and promote international technical exchanges and cooperation of tropical diseases.

OBJECTIVE To systematically evaluate medication risk prediction models for hospitalized adult patients and provide references for their development and clinical application. METHODS Databases including PubMed， Embase， Web of Science， CNKI， Wanfang data， VIP and CBM were searched for studies on medication risk prediction models from their inception to May 2024. After screening the literature， extracting data， and evaluating the quality of the literature， descriptive analysis was performed on the results of the included studies. RESULTS A total of 13 studies were included， involving 12 models. Nine studies used Logistic regression algorithm for modeling， and the number of included predictive factors ranged from 3 to 11； the area under the receiver operating characteristic curve ranged from 0.65 to 0.865. The literature quality evaluation results showed that 10 studies had high risk of bias； 10 studies had high applicability risk. A total of 31 predictive factors were extracted， including 15 items of basic patient information， 3 test indicators， and 5 items of medication information， and 8 others. CONCLUSIONS The existing medication risk prediction models for hospitalized adult inpatients are mainly Logistic regression algorithm， with predictive factors mainly focusing on basic indicators such as demographics. The overall prediction performance of the models needs to be improved， and the overall risk of bias is relatively high.

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide, with above 80% of cases be non-small cell lung cancer (NSCLC), among which lung squamous cell carcinoma (LUSC) occupies a significant proportion. Although comprehensive cancer therapies have considerably improved the overall survival of patients, patients with advanced LUSC have a poorer prognosis. Therefore, there is a need for a biomarker to predict the progress of advanced LUSC in order to improve prognosis through early diagnosis. Previous studies have shown that miRNAs are differentially expressed in lung cancer tissues and play roles as potential oncogenes or tumor suppressors. The aim of this study is to identify differentially expressed miRNAs between early-stage and advanced-stage LUSC, and to establish a set of miRNAs that can predict the progress of advanced LUSC. METHODS: Clinical data and miRNA-related data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatic methods were applied to analyze the data. Receiver operating characteristic (ROC) curves were plotted, and various online tools were used to predict target genes, with subsequent analysis of the potential biological mechanisms of these genes. RESULTS: A total of 58 differentially expressed miRNAs were identified between the experiment group and the control group. Seven miRNAs were selected for potential construction of a miRNA biomarker through LASSO regression, and based on the area under the curve (AUC) values of each miRNA, four of these miRNAs (miR-377-3p, miR-4779, miR-6803-5p, miR-3960) were ultimately chosen as biomarkers for predicting advanced LUSC. The AUC under the ROC curve for the combined four miRNAs was 0.865. Enrichment analysis showed that these target genes were involved in several pathways, including cancer-related pathways, mitogen-activated protein kinase (MAPK) signaling pathway, serine/threonine kinase, and tyrosine kinase signaling pathways. CONCLUSIONS The combined use of miR-377-3p, miR-4779, miR-6803-5p and miR-3960 provides a good predictive ability for the progress of advanced LUSC patients, with an AUC of 0.865.
Humans ; MicroRNAs/metabolism* ; Lung Neoplasms/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Prognosis ; ROC Curve ; Middle Aged