The guideline and item classification approach represents a distinct historical method ology, first introduced by ZHU Xi in his Compendium of Comprehensive Mirror for Aid in Government during the Southern Song Dynasty. LOU Ying later adapted this framework to the field of traditional Chinese medicine, critically analyzing and addressing the limitations of prior academic theories. By drawing upon the rich intellectual traditions of classical texts and historical works, LOU Ying restructured and refined his ideas, ultimately establishing the "guideline and item" medical theory. This innovative framework profoundly influenced LOU Ying′s work, shaping both the compilation of medical texts and the development of novel theoretical approaches in traditional Chinese medicine. In disease differentiation and treatment, LOU Ying proposed the theory of guideline and item classification, that is, taking yin and yang as two guidelines, taking qi and blood, exterior and interior, upper and lower parts, deficiency and excess, cold and heat as ten items, and constructing a syndrome differentiation system focusing on qi and blood, focusing solely on upper and lower parts, distinguishing exterior and interior, carefully examining deficiency and excess, and distinguishing cold and heat. The guideline and item classification system integrates and harmonizes multiple syndrome differentiation method ologies, including the eight-principle pattern identification, viscera syndrome differentiation, differentiation of syndromes according to the pathogenesis of Sanjiao, and qi-blood-fluid pattern identification. As a precursor to modern method of syndrome differentiation and treatment, it possesses unique theoretical significance and considerable clinical relevance. Its applicability to diagnosing and treating various diseases, coupled with its greater operational practicality compared to other methods, highlights its value in contemporary clinical practice. This system offers a complementary and enhanced framework for syndrome differentiation and treatment, warranting further adoption and promotion in the clinical setting.

ObjectiveTo explore the mechanism of Buzhong Yiqitang on pyroptosis in autoimmune thyroiditis （AIT） mice based on the NOD-like receptor hot protein domain related protein 3 （NLRP3）/cysteinyl aspartate specific proteinase-1（Caspase-1）/Gasdermin D （GSDMD） pathway. MethodSixty NOD.H-2^h4 mice were divided into normal group， model group， low， medium， and high dose groups （4.10， 8.19， 16.38 g·kg^-1）of Buzhong Yiqitang， and selenium yeast tablet group （0.26 mg·kg^-1）， with 10 mice in each group. Except for the normal group， all other groups were given 0.05% NaI by gavage for eight weeks to establish a model and then received the drug treatment for eight weeks. The serum levels of thyroid peroxidase antibody （TPO-Ab） and thyroglobulin antibody （TgAb） were detected using enzyme-linked immunosorbent assay （ELISA） method. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in mouse thyroid tissue. The immunohistochemical method was used to detect the protein expression of NLRP3， Caspase-1， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of NLRP3， Caspase-1， IL-1β， and IL-18. Western blot was used to detect the levels of pyroptosis-related proteins in thyroid tissue. ResultCompared with the normal group， the serum levels of TPO-Ab and TgAb in the model group were significantly increased （P<0.01）. Thyroid follicles either increased in a cubic shape or were damaged and atrophied， with a large number of lymphocytes infiltrating around the follicles. Compared with the model group， the levels of TPO-Ab and TgAb in other groups were significantly reduced （P<0.01）， and the morphology and structure of follicles were improved. The degree of lymphocyte infiltration was reduced. Among them， the medium dose group of Buzhong Yiqitang had the most significant reduction and improvement effect. Compared with the normal group， the positive products and mRNA expression of NLRP3， Caspase-1， IL-1β， and IL-18 proteins in the thyroid tissue of the model group significantly increased （P<0.01）， and the protein expression levels of NLRP3， cleaved Caspase-1， IL-1β， IL-18， and GSDMD-N were significantly increased （P<0.05， P<0.01）. Compared with the model group， the positive products and mRNA expression of NLRP3， Caspase-1， IL-1β， and IL-18 proteins in other groups were significantly reduced （P<0.05， P<0.01）， with the most significant reduction effect in the medium dose group of Buzhong Yiqitang. The protein expression levels of NLRP3， cleaved Caspase-1， IL-1β， IL-18， and GSDMD-N were significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can improve AIT， and its mechanism may be achieved by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to inhibit pyroptosis.

BACKGROUND:Minipigs are often used in research fields such as skin injury,vascular trauma and cosmetic medicine because they are highly similar to human beings in terms of skin tissue structure and cardiovascular system.Hydrogel as a wound repair drug possesses a variety of excellent physicochemical properties such as strong water retention and adhesion,which can provide isolation moisturization and drug release for wounds. OBJECTIVE:To summarize and conclude the progress of the application of trauma models for different experimental purposes of hydrogel therapy for minipigs,to reveal the development status of various types of minipig trauma models,to analyze the deficiencies of minipig trauma models at the present stage. METHODS:The relevant articles published in Web of Science database and CNKI database from the establishment of each database to 2023 were checked,using"piglet,miniature pig,minipig,miniature pig;gel,hydrogel;trauma,injury,wound,lesion,incision"as Chinese search terms and"Miniature Swine,Miniature pig,minipig;gel,hydrogel;injury,wound,lesion,incision"as English search terms.A total of 438 Chinese and English documents were retrieved,and 59 documents were included in the study through the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)At present,the main models used clinically for trauma repair are large animal species(dogs and pigs),rabbits,and rodents(rats and mice).Because the skin structure of the minipig is more like that of humans,the minipig is the most ideal animal model for trauma repair.(2)In the in-vitro skin injury model,skin defect model is the basic wound model,which can be divided into full skin defect model and medium-thickness skin defect model according to the depth of the wound defect.Burn wound model and infected wound model are multidimensional models with hot metal scald and bacterial culture imposed on the basis of the skin defect model,which have the advantages of high safety coefficient and low operation difficulty.(3)In the in-vivo trauma repair model,mini-pigs are used as esophageal cricothyrotomy model which is more in line with the pathological state of clinical diseases.Mini-pigs are used in the gastric perforation and vascular hemostasis model,which can visually demonstrate the stronger organ adhesion,hemostatic properties and tissue regeneration-promoting effects of the hydrogel.(4)The specific parts of the pig also has the corresponding mode of use:pig ear is usually used to evaluate the hydrogel drug delayed-release effect.Porcine cellular proteins and pig skin collagen are mostly used to prepare composite hydrogels of tissue origin.

ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 （Th17）/regulatory T cell （Treg） and Notch1 signaling pathway in mice with autoimmune thyroiditis （AIT）. MethodA total of 60 8-week-old NOD.H-2^h4 mice were randomly divided into the normal group， model group， western medicine group （selenium yeast tablet， 32.5 mg·kg^-1）， and low-dose （4.78 g·kg^-1·d^-1）， middle-dose （9.56 g·kg^-1·d^-1）， and high-dose （19 g·kg^-1·d^-1） Buzhong Yiqitang groups， with 10 mice in each group. The normal group was fed with distilled water， and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously， the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies （TGAb）， thyroid-stimulating hormone （TSH）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were detected by enzyme-linked immunosorbent assay （ELISA）， and thyroid tissue changes were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt （RORγt）， interleukin （IL）-17， forkhead box P3 （FoxP3）， IL-10， Notch1， and hair division-related enhancer 1 （Hes1） in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the thyroid structure of the model group was severely damaged， and lymphocytes were infiltrated obviously. The levels of serum TGAb， FT3， and FT4 contents were significantly increased， and TSH content was significantly decreased （P<0.01）. The mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were significantly increased， while those of FoxP3 and IL10 were significantly decreased in the model group （P<0.01）. Compared with the model group， thyroid structural damage and lymphocyte infiltration were improved in the treatment groups， and serum TGAb， FT3， and FT4 contents were significantly decreased. TSH content was increased， and mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees （P<0.05， P<0.01）， and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice， and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.

【Objective】 To investigate the prognostic value of tumor location in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU), and to develop and validate a nomogram model for predicting the overall survival (OS). 【Methods】 UTUC patients undergoing RUN at our hospital during Jan.2010 and Dec.2022 were retrospectively collected, 70% of whom were included in the training group and 30% in the validation group.According to the tumor location, patients were divided into renal pelvis tumor (RPT) group and ureteral tumor (UT) group.The differences in clinicopathological features and prognosis were analyzed.Based on multivariate Cox results, a nomogram model for predicting OS was developed and validated. 【Results】 A total of 366 patients (196 RPT and 170 UT) were included in this study.There were statistically significantly differences in urine cytology (P=0.001), hydronephrosis (P<0.001), history of bladder tumor (P=0.021), pathological T stage (P<0.001) and histological structure (P=0.037) between the two groups.Multivariate Cox results showed that patients with UT had a worse prognosis (HR=2.00, 95%CI: 1.22-3.27, P=0.006).Factors of the nomogram for predicting OS included age, tumor location, lymphovascular invasion and pathological T stage.The model showed good discrimination and calibration, and performed well in internal verification. 【Conclusion】 Compared with RPT, UT has a worse prognosis and the fat around the tumor should be surgically removed more thoroughly to avoid micro-residual.We successfully coustructed a nomogram model that can be used to predict the OS of UTUC patients after RNU surgery.

Objective To evaluate the value of systemic inflammatory markers(SIM)in the prognosis of patients with bladder cancer undergoing radical cystectomy.Methods Clinical data of 233 patients with bladder cancer who underwent radical cystectomy in the Affiliated Hospital of Xuzhou Medical University during Dec.2011 and Nov.2020 were retrospectively collected,the SIM score was calculated and patients were grouped.Progression-free survival(PFS)was assessed with Kaplan-Meier analysis,and differences between groups were compared with log-rank test.Factors affecting PFS were analyzed with Cox proportional risk model.The patients were randomly divided into a training set(n=164)and a verification set(n=69)according to 7:3 ratio,and a nomogram model was established and verified.Results Cox regression analysis showed that SIM score and pathological T staging were independent predictors of PFS(P＜0.05).A predictive model was established based on SIM score and pathological T staging.The area under the receiver operating characteristic(AUC)curve for predicting 1-year,3-year,and 5-year PFS were 0.939,0.943,and 0.943,respectively.After the model was applied to evaluate the validation set,the performance was still stable.Conclusion The prediction model based on SIM score and clinicopathological T staging can accurately predict the survival of patients with bladder cancer after radical cystectomy,and can be used to guide individualized treatment of patients.

ObjectiveTo explore the mechanism of Buzhong Yiqitang in ameliorating inflammatory injury in autoimmune thyroiditis (AIT) mice based on the Toll-like receptor 4（TLR4）/nuclear transcription factor-kappa B（NF-κB）/absent in melanoma 2（AIM2）inflammasome signaling pathway. MethodThe 120 genetically susceptible 8-week-old NOD.H-2^h4 mice were selected and randomly divided into control group， model group， low， medium and high dose groups of Buzhong Yiqitang （4.78， 9.56， 19.12 g·kg^-1）， and western medicine group （selenium yeast tablets， 3.033×10^-5 g·kg^-1）. The AIT model mice in each group drank ad libitum 0.05% sodium iodide aqueous solution for 8 weeks to establish the AIT model， and the control group drank ad libitum distilled water. Eight weeks later， the mice in each dosing group were divided into groups and gavage. The swelling of thyroid tissue was observed with the naked eye， and the weight of spleen was weighed. The content of serum inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， and Real-time PCR was used to detect the expression of HMGB1， TLR4， AIM2， NF-κB p65，apoptosis-associated speck-like protein（ASC），cysteinyl aspartate-specific protease-1（Caspase-1）， IL-1β mRNA. Western blot was used to detect the expression of high motility group protein 1 （HMGB1）， TLR4， AIM2， NF-κB p65， phosphorylation（p）-NF-κB p65， ASC， Caspase-1， and IL-1β proteins in thyroid tissue， and immunofluorescence staining was used to observe the protein expression of HMGB1， AIM2， and NF-κB p65 in thyroid tissue of mice. ResultCompared with the control group， the thyroid tissue of mice in the model group was significantly swollen， the spleen quality was significantly increased， and the expression of HMGB1， TLR4， NF-κB p65， AIM2， ASC， Caspase-1， IL-1β in thyroid tissue was significantly increased （P<0.01）. Compared with the model group， the swelling of thyroid tissue in mice in each dose group of Buzhong Yiqitang was improved， the quality of spleen was significantly reduced， and the expression of HMGB1， TLR4， AIM2， NF-κB p65， p-NF-κB p65， ASC， Caspase-1， IL-1β in thyroid tissue was significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and regulating the abnormal activation of the TLR4/NF-κB/AIM2 inflammasome signal pathway may be one of its intervention mechanisms.

ObjectiveTo investigate the mechanism of Buzhong Yiqitang in ameliorating ferroptosis in autoimmune thyroiditis （AIT） mice based on the nuclear factor erythroid 2-related factor 2 （Nrf2）/peroxisome proliferator-activated receptor γ （PPARγ）/glutathione peroxidase 4 （GPX4） pathway. Method120 SPF-grade 7-8-week-old NOD.H-2^h4 mice were randomly divided into control group， model group， low-， medium-， and high-dose Buzhong Yiqitang groups， and western medicine group， with 20 mice in each group. Except for the control group， all mice were fed with classic high-iodine water （0.05% NaI） to induce AIT models after 8 weeks. The low-， medium-， and high-dose Buzhong Yiqitang groups were administered 4.78， 9.56， 19.12 g·kg^-1 of Buzhong Yiqitang， respectively， via gavage. The western medicine group was given 3.033×10^-5 g·kg^-1 selenium yeast tablet suspension via gavage， while the control and model groups were given an equal volume of distilled water via gavage. After 8 weeks of continuous treatment， samples were collected. The pathological morphology of mouse thyroid tissue was observed through hematoxylin-eosin （HE） staining，the content of serumantithyroid peroxidase autoantibody（TPOAb）and anti-thyroglobulin antibodies（TGAb）was measured by enzyme-linked immunosorbent assay （ELISA），the kit was used to detect the levels of superoxide dismutase （SOD）， and malondialdehyde （MDA） in mouse serum. Immunofluorescence was used to detect the localized expression of GPX4 in thyroid tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of Nrf2， PPARγ， solute carrier family 7 member 11 （SLC7A11）， solute carrier family 3 member 2 （SLC3A2）， lysolipid lecithin acyltransferase 3 （LPCAT3）， and GPX4 mRNA in thyroid tissue. Western blot was used to detect the expression of Nrf2， PPARγ， SLC7A11， SLC3A2， LPCAT3， and GPX4 proteins in thyroid tissue. ResultCompared with control group， model group under light microscopy showed significant lymphocyte infiltration in the thyroid tissue， significantly increased levels of TGAb and TPOAb in serum （P<0.01）， significantly increased MDA levels and decreased SOD levels in serum （P<0.01）， significantly decreased expression of Nrf2， PPARγ， SLC7A11， SLC3A2， and GPX4 （P<0.01） in thyroid tissue， while the expression of LPCAT3 was significantly increased （P<0.01）. Compared with model group， the Buzhong Yiqitang groups and the western medication group under light microscopy showed lymphocyte infiltration in the thyroid tissue of was decreased， significantly decreased levels of TPOAb and TGAb in serum （P<0.05，P<0.01）， decreased MDA levels and increased SOD levels in serum（P<0.05，P<0.01），significantly increased expression of Nrf2， PPARγ， SLC7A11， SLC3A2， and GPX4， while the expression of LPCAT3 was significantly decreased （P<0.05，P<0.01） in the thyroid tissue. Compared with western medication group， Buzhong Yiqitang groups showed significant overall trends in the expression of Nrf2， PPARγ， SLC7A11， SLC3A2， GPX4， and LPCAT3 （P<0.05，P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and its mechanism of action may be related to the regulation of Nrf2/PPARγ/GPX4 to inhibit ferroptosis.

ObjectiveTo explore the mechanism of Buzhong Yiqitang in improving autoimmune thyroiditis （AIT） by regulating helper T cell 17（Th17） cells through microRNA-155 （miR-155）/Nedd4 family interaction protein 1 （Ndfip1）/phosphatase and tensin homology （Pten） axis. MethodThe 100 SPF grade 8 week-old NOD.H-2^h4 mice were fed with high iodine water （0.05% NaI） for 8 weeks， and AIT model was made. They were divided into model group， Buzhong Yiqitang low-，medium-，and high-dose groups （4.78，9.56，19.12 g·kg^-1·d^-1） and selenium yeast tablet group （3.033×10^-5 g·kg^-1） according to random number table method. There were 20 mice in each group and 20 mice in the control group. The control group and the model group were given the same amount of distilled water. After 8 weeks of continuous administration， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of miR-155-5p， Ndfip1， Pten， protein tyrosine kinase 1 （Jak1）， signaling and transcriptional activator 3 （Stat3） retinoic acid-associated orphan receptor γt （RORγt）， and interleukin-17 （IL-17） mRNA in mouse thyroid tissue. Western blot was used to detect the expression of Ndfip1， Pten， Jak1， Stat3， RORγt， and IL-17 proteins in mouse thyroid tissue， immunohistochemical method was used to detect the expression of Ndfip1 and Pten proteins in mouse thyroid tissue； flow cytometry was used to detect the proportion of Th17 cells in mouse spleen. ResultCompared with the control group， the proportion of Th17 cells was increased （P<0.01）. The expressions of miR-155-5p， Jak1， Stat3， RORγt and IL-17 were increased （P<0.01）， while the expressions of Ndfip1 and Pten were decreased （P<0.01）. Compared with model group， the proportion of Th17 cells was decreased （P<0.05，P<0.01）. The expressions of miR-155-5p， Jak1， Stat3， RORγt and IL-17 were decreased （P<0.05，P<0.01）， while the expressions of Ndfip1 and Pten were increased （P<0.05，P<0.01）. ConclusionThe application of Buzhong Yiqitang can improve the autoimmune disorder of AIT mice， the mechanism of which may be related to the regulation of Ndfip1/Pten axis by miR-155 and then the regulation of Th17 cell differentiation.

ObjectiveTo investigate the effects of Buzhong Yiqitang on the tumor necrosis factor receptor superfamily member 6 （Fas）/Fas related death domain protein （FADD）/Caspase-8 cell apoptotic signaling pathway in mice model with autoimmune thyroiditis （AIT）. MethodThere were 120 SPF grade NOD.H-2^h4 mice aged 8 weeks， 100 of which were fed with high iodine water （0.05% NaI）， and the AIT model was made after 8 weeks. According to random number table method， they were divided into model group， Buzhong Yiqitang low-dose， medium-dose and high-dose groups （4.78， 9.56， 19.12 g·kg^-1）， selenium yeast tablet group （3.033×10^-5 g·kg^-1）， with 20 mice in each group and 20 control group. The apoptosis of thyroid cells was detected by in situ end labeling （TUNEL） after 8 weeks of administration. The real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Fas， FADD， Caspase-8， and Caspase-3 in thyroid tissue. Western blot was used to detect the protein expression of Fas， FADD， Caspase-8， Caspase-3， cleaved Caspase-8， and cleaved Caspase-3 in thyroid tissue， and the immunohistochemical method was used to detect the protein expression of Fas and Caspase-3 in thyroid tissue. ResultCompared with control group， there were more positive expressions of apoptotic cells in model group under fluorescence microscope， and the expressions of Fas， FADD， Caspase-8， Caspase-3， cleaved Caspase-8 and cleaved Caspase-3 were significantly increased （P<0.05， P<0.01）. Compared with model group， the positive expression of thyroid apoptotic cells in each administration group was decreased under fluorescence microscope， and the expressions of Fas， FADD， Caspase-8， Caspase-3， cleaved Caspase-8， cleaved Caspase-3 were significantly decreased （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve thyroid cell apoptosis and inflammatory injury in AIT mice. The mechanism may be related to the inhibition of Fas/FADD/Caspase-8 signaling pathway.