The Dunhuang manuscript Fuxing Jue takes the "Tangye Jingfa Tu" as the core of its theory on prescription and compatibility. Its medication principles mainly include the "five elements principle of tonifying and purging" and the "five elements principle of elimination and transformation". Based on the differentiation of deficiency and excess in the five Zang organs， it flexibly applies medicinal properties， usage， and flavor transformation for tonifying and purging， forming its unique method of medication and compatibility. In Taiyin disease， "fullness syndrome" often occurs together with "diarrhea"， and these two conditions also serve as the primary indications for the middle-regulating formulas. Among them， Lizhong Wan （Tang） mainly address Taiyin deficiency. The three Xiexin Tang （Banxia Xiexin Tang， Gancao Xiexin Tang， Shengjiang Xiexin Tang） address Taiyin deficiency accompanied by pathogenic excess. The Sini Tangand Tongmai Sini Tang primarily treat dysfunction of the liver， spleen， and kidney with impaired opening and closing of Taiyin， manifesting as diarrhea. The medicinal flavors of middle-regulating formulas are pungent， sweet， and bitter， acting directly on the spleen of Taiyin. The pungent flavor induces purging of the spleen， sweet flavor tonifies the spleen， and bitter flavor eliminates lumps. When the constituent medicinal units of middle-regulating formulas are unified， the ratio of pungent to sweet flavors reflects the tonic and purgative strength of the formula. In addition， the two decoction methods， "short-term decoction to extract Qi" and "long-term decoction to extract flavor"， also influence the formula's tonifying and purgative effects. Based on the composition of flavors and special decoction methods， this article discusses the differences in the use of middle-regulating formulas for treating "“fullness syndrome" versus "diarrhea". Dysfunction of the spleen can give rise to various diseases. Therefore， middle-regulating formulas are not limited to treating "deficiency， cold， and dampness" syndromes. Later generations of physicians further modified Lizhong Tang to treat "excess， heat， and dryness" syndromes， laying a solid foundation for more flexible and effective clinical application of middle-regulating formulas.

The Dunhuang manuscript Fuxing Jue takes the "Tangye Jingfa Tu" as the core of its theory on prescription and compatibility. Its medication principles mainly include the "five elements principle of tonifying and purging" and the "five elements principle of elimination and transformation". Based on the differentiation of deficiency and excess in the five Zang organs， it flexibly applies medicinal properties， usage， and flavor transformation for tonifying and purging， forming its unique method of medication and compatibility. In Taiyin disease， "fullness syndrome" often occurs together with "diarrhea"， and these two conditions also serve as the primary indications for the middle-regulating formulas. Among them， Lizhong Wan （Tang） mainly address Taiyin deficiency. The three Xiexin Tang （Banxia Xiexin Tang， Gancao Xiexin Tang， Shengjiang Xiexin Tang） address Taiyin deficiency accompanied by pathogenic excess. The Sini Tangand Tongmai Sini Tang primarily treat dysfunction of the liver， spleen， and kidney with impaired opening and closing of Taiyin， manifesting as diarrhea. The medicinal flavors of middle-regulating formulas are pungent， sweet， and bitter， acting directly on the spleen of Taiyin. The pungent flavor induces purging of the spleen， sweet flavor tonifies the spleen， and bitter flavor eliminates lumps. When the constituent medicinal units of middle-regulating formulas are unified， the ratio of pungent to sweet flavors reflects the tonic and purgative strength of the formula. In addition， the two decoction methods， "short-term decoction to extract Qi" and "long-term decoction to extract flavor"， also influence the formula's tonifying and purgative effects. Based on the composition of flavors and special decoction methods， this article discusses the differences in the use of middle-regulating formulas for treating "“fullness syndrome" versus "diarrhea". Dysfunction of the spleen can give rise to various diseases. Therefore， middle-regulating formulas are not limited to treating "deficiency， cold， and dampness" syndromes. Later generations of physicians further modified Lizhong Tang to treat "excess， heat， and dryness" syndromes， laying a solid foundation for more flexible and effective clinical application of middle-regulating formulas.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Objective To explore the adverse event signals of children using macrolide drugs （azithromycin, clarithromycin, and erythromycin）, and provide reference for rational medicine use in clinical practice. Methods Data from children under 12 years old were extracted from the US FAERS database spanning from the first quarter of 2004 to the second quarter of 2023. The adverse drug reaction （ADR） signal mining for three macrolide antibiotics was conducted using the Reporting Odds Ratio （ROR） and Bayesian Confidence Propagation Neural Network （BCPNN） methods. Special emphasis was placed on analyzing and contrasting the differences in adverse events among the three drugs. Results A total of 1 615 reports for children under 12 years old were retrieved from the FAERS database, including 1 024 reports of azithromycin, 460 reports of clarithromycin, and 131 reports of erythromycin. Among azithromycin and erythromycin, there were more reports from boys than girls, while for clarithromycin, there were more reports from girls than boys. Oral administration was the most common route of administration for all three drugs. Regarding the outcome of adverse events reported, azithromycin and clarithromycin were primarily associated with other serious adverse events, whereas erythromycin was mainly associated with hospitalization and other serious adverse events. The number of adverse events reported decreased with increasing age, with a higher number of reports in the 0-3 age group. Using the ROR and BCPNN methods for signal detection, 86 signals were identified for azithromycin, 91 for clarithromycin, and 34 for erythromycin. These signals involved 22 System Organ Classes （SOCs）, with azithromycin mainly concentrated in skin and subcutaneous tissue disorders （n=21）, clarithromycin in gastrointestinal disorders （n=15）, and erythromycin in gastrointestinal disorders （n=8）. Twenty-four signals of moderate to high risk were detected, with 13 for azithromycin, 9 for clarithromycin, and 2 for erythromycin. Conclusion The adverse events induced by the three drugs with different risks in different systems. When clinically treating Mycoplasma pneumoniae pneumonia in children, the risk profiles of drugs in different systems should be considered, and personalized dosing should be implemented.

The development of the rare disease discipline is a crucial pathway for enhancing the diagnosis and treatment of rare diseases, cultivating specialized professionals, and fostering technological innovation. Currently, China' rare disease discipline is accelerating its development driven by both policy and demand. However, it still faces multi-dimensional challenges, including an incomplete clinical management mechanism, a shortage of interdisciplinary talents, a weak scientific research system, and limited outreach capacity. To address these challenges, this paper proposes and constructs an integrated development system with clinical diagnosis and treatment as the foundation, talent cultivation as the engine, scientific research as the support, and disciplinary outreach capacity as the extension. Specific strategies include: enhancing clinical management through artificial intelligence-assisted diagnosis systems and multidisciplinary collaboration platforms; strengthening the talent pool through textbooks, curricula, and hierarchical training mechanisms; bolstering research collaboration and translational outcomes by leveraging international data-sharing platforms, national rare disease medical centers, the State Key Laboratory of Complex Severe and Rare Diseases, and the National Key Scientific Infrastructure for Translational Medicine; and expanding grassroots outreach and public awareness through the National Rare Disease Diagnosis and Treatment Collaboration Network, the National Rare Disease Quality Control Center, and integrated media communication channels. In the future, the rare disease discipline should further deepen the integration of medicine and engineering, expand international cooperation, focus on the translational closed loop, improve the regional collaboration network, so as to build a more resilient and dynamic disciplinary ecosystem, and ultimately achieve a comprehensive improvement in the diagnosis and treatment of rare diseases.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

To evaluate the application value of the Peyton four-step teaching method in the standardized training of intestinal ultrasound and compare it with traditional teaching methods, so as to provide an optimized approach for clinical ultrasound training.

Objective: To develop a prediction model for mild cognitive impairment (MCI) risk among the elderly, so as to provide a tool for MCI early screening. Methods : From July 2022 to September 2024, a multi-stage stratified random cluster sampling method was used to recruit permanent residents aged ≥65 years from the Xinjiang Uygur Autonomous Region as study participants. Data on sociodemographic characteristics, nutritional status, body composition indices, bone mineral density, and handgrip strength were collected through questionnaires and physical examinations. Sarcopenia was defined based on appendicular skeletal muscle index and handgrip strength. MCI was assessed using the Mini-Mental State Examination, with adjustments for educational level. Participants were randomly divided into a training set and a validation set in a 7∶3 ratio. LASSO regression and multivariable logistic regression models were employed to screen for predictors and construct an MCI risk prediction model. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 1 641 participants were surveyed, including 755 males (46.01%) and 886 females (53.99%). The majority of participants were aged 65-<75 years, comprising 1 154 individuals (70.32%). MCI was detected in 517 participants, corresponding to a detection rate of 31.51%. Resultsfrom LASSO regression and multivariate logistic regression analysis showed that residence (rural, OR = 2.323, 95% CI: 1.682-3.210), age (75-<85 years, OR = 1.405, 95% CI: 1.019-1.937; ≥85 years, OR = 3.655, 95% CI: 1.696-7.875), educational level (primary school, OR = 0.341, 95% CI: 0.247-0.472; junior high school, OR = 0.255, 95% CI: 0.160-0.408; high school, OR = 0.286, 95% CI: 0.154-0.531; bachelor's degree or above, OR = 0.120, 95% CI: 0.041-0.351), history of alcohol consumption (yes, OR = 3.216, 95% CI: 2.164-4.779), risk of malnutrition (yes, OR = 1.464, 95% CI: 1.064-2.014), sarcopenia (yes, OR = 3.197, 95% CI: 2.332-4.385), and waist-to-hip ratio (abnormal, OR = 1.540, 95% CI: 1.159-2.048) were identified as predictive factors for MCI among the elderly. In the training set, the area under the ROC curve, sensitivity, and specificity were 0.788, 0.719, and 0.712, respectively. In the validation set, the corresponding values were 0.784, 0.913, and 0.542, respectively. DCA demonstrated that the model provided a higher clinical net benefit for predicting MCI risk when the risk threshold probability ranged from 0.124 to 0.764. Conclusion The prediction model developed in this study demonstrates good discriminative ability and clinical utility, indicating its substantial value for predicting the MCI risk among the elderly.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

ObjectiveTo evaluate the clinical efficacy and economic value of the Jiangsu Traditional Chinese Medicine （TCM） Diagnosis and Treatment Protocol for Dominant Diseases （abbreviated as the Diagnosis and Treatment Protocol） in adult patients with non-severe community-acquired pneumonia （CAP） based on real-world clinical data. MethodsA retrospective real-world cohort study was conducted using electronic medical records of adult patients hospitalized for non-severe CAP from September 1st， 2023 to December 31st， 2024 across 10 TCM hospitals in Jiangsu province. Patients were classified into an exposure group and a non-exposure group based on whether they received Chinese herbal medicine （CHM） according to the Diagnosis and Treatment Protocol. The non-exposure group received only conventional western medicine， while the exposure group additionally received differentiated CHM for at least five consecutive days. Outcomes were compared between two patient groups， including cough resolution rate， sputum resolution rate （assessed by volume， color， and consistency）， incidence of abnormal C-reactive protein （CRP）， incidence of abnormal white blood cell （WBC） count， and radiographic resolution rate of pulmonary infiltrates on chest imaging. Multivariable logistic regression was performed to identify factors influencing clinical efficacy. Subgroup analyses were conducted according to age， gender， smoking status， history of hypertension， and pneumonia severity score （CURB-65）， and the efficacy of treatment for cough and sputum was analyzed within each subgroup. Cost-effectiveness analysis was conducted using cough resolution rate as the outcome measure， evaluating the pharmacoeconomics of the two groups. ResultsA total of 1688 patients were included with 1293 in the exposure group and 395 in the non-exposure group. Compared to the non-exposure group， the exposure group demonstrated significantly higher resolution rates of cough， sputum volume， color， and consistency， as well as a significantly lower incidence of abnormal CRP （P＜0.05）. No statistically significant difference was observed between the groups in terms of abnormal WBC count and radiographic resolution rate of pulmonary infiltrates （P＞0.05）. Logistic regression analysis showed that the cough resolution rate in the exposure group was 1.83 times that of the non-exposure group， while the probabilities of resolution in sputum volume， color， and consistency were 1.37， 2.09， and 1.56 times those of the non-exposure group， respectively （P＜0.05）. Subgroup analyses showed that the exposure group achieved significantly higher cough resolution rates across most subgroups except for populations with a CURB-65 score ≥2 or those with a history of hypertension （P＜0.05）. Specifically， among females， patients aged ≥18 and ＜65 years， non-smokers， those without hypertension， and those with a CURB-65 score of 0， the exposure group showed a higher cough resolution rate than the non-exposure group （P＜0.05）. From an economic perspective， total hospitalization cost， length of stay， antibiotic cost， and CHM cost all differed significantly between groups （P＜0.05）. The cost-effectiveness ratio （CER） was 10,788.80 CNY/case in the exposure group， while 22,513.80 CNY/case in the non-exposure group. This implies that， compared with the exposure group， the non-exposure group incurred an additional 17,302.27 CNY to achieve one case of cough resolution. When the willingness-to-pay threshold ranged from 0 to 50,000 CNY， the probability of economic advantage was consistently higher in the exposure group than in the non-exposure group. ConclusionOn the basis of conventional western medicine， the addition of CHM in accordance with the Diagnosis and Treatment Protocol can effectively improve clinical symptoms， reduce inflammatory markers， promote clinical recovery， and is more cost-effective in treating adults with non-severe CAP.