This paper summarizes Professor DING Ying's clinical experience in the treatment of systemic lupus erythematosus （SLE） through differentiation of three states， yin fire， latent fire， and fire toxin. It is proposed that fire pathogenic factors constitute a key pathological element running throughout the entire disease course of SLE. The evolution of its pathogenesis centers on these three states， spleen-kidney deficiency with the initial emergence of yin fire as the onset of disease， damage to yin by medicinal toxicity with internal blazing of latent fire as the driver of disease progression， and the interlocking of blood stasis and heat with intense scorching by fire toxin as the critical factor leading to severe and life-threatening conditions. Corresponding to these three stages， targeted prescriptions are formulated， Jiuwei Yishen Formulation （九味益肾方） to tonify the spleen and kidney， raise yang， and disperse fire； Ziyin Xiehuo Decoction （滋阴泄火汤） to nourish yin and fluids while clearing latent fire； and Santeng Changluo Jiedu Decoction （三藤畅络解毒汤） to dispel blood stasis， unblock the collaterals， detoxify， and restrain fire. This staged and integrated therapeutic strategy aims to address both root and branch and to achieve overall regulation， providing valuable guidance for the clinical differentiation and treatment of SLE.

ObjectiveTo identify potential influencing factors of urate crystal deposition at ankle/foot in patients with hyperuricemia （HUA）， and to analyze the predictive value of inflammatory indicators for urate crystal deposition in patients with different traditional Chinese medicine （TCM） syndromes， so as to provide potential reference for clinical risk assessment and individualized TCM intervention. MethodsA retrospective study was carried out with the enrollment of 231 HUA patients from The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2021 and December 2024. The enrolled patients were further divided into a crystal deposition-positive group （143 cases） and a crystal deposition-negative group （88 cases） according to the results of dual-energy computed tomography （CT）. Sociodemographic data， living habits， serum uric acid levels， and inflammatory indicators of the enrolled patients were collcted， and TCM syndrome differentiation was performed. Furthermore， univariate analysis was used to compare inter-group differences in clinical characteristics. MMultivariate Logistic regression was applied to identify the influencing factors of urate crystal deposition. In addition， the receiver operating characteristic （ROC） curves were plotted to evaluate the predictive efficacy of inflammatory indicators for crystal deposition across different TCM syndromes. ResultsThere were statistically significant inter-group differences in the proportion of males， age， body mass index， proportion of mental labor， rate of low water intake， and rate of high-sugar beverage consumption （P<0.05），whereas no significant difference in low exercise intensity was found between the two groups. Furthermore， compared with the negative group， the positive group had higher serum uric acid level， neutrophil-to-lymphocyte ratio （NLR）， and platelet-to-lymphocyte ratio （PLR）， but lower systemic immune-inflammation index （SIRI） （P<0.05）. Regarding the distribution of TCM syndromes， the positive group was dominated by the dampness-heat accumulation syndrome （55/143，38.46%）， while the negative group was mainly characterized by the phlegm-turbidity obstruction syndrome （44/88，50.00%）. Multivariate Logistic regression analysis revealed that high-sugar beverage consumption， elevated NLR， and elevated PLR were risk factors for urate crystal deposition ［odd ratio （OR） = 8.002， 5.377， 1.034， respectively； 95% CI 1.572-40.732， 2.179-13.270， 1.013-1.054，all P<0.05］， while SIRI was a protective factor （OR = 0.869， 95% CI 0.778-0.971， P<0.05）. In the positive group， patients with the dampness-heat accumulation syndrome exhibited the highest NLR， while the lowest PLR and SIRI， showing statistically significant differences with those of other syndromes （all P<0.05）. In addition， ROC curve analysis indicated that for the dampness-heat accumulation syndrome， the combined "NLR + PLR" model had an area under the curve （AUC） of 0.901 （95% CI 0.850-0.951， P<0.01）， with a sensitivity of 89.1% and a specificity of 79.5%； for the blood stasis-heat obstruction syndrome， the combined "NLR + PLR" model had an AUC of 0.880 （95% CI 0.825-0.934， P<0.01）， with a sensitivity of 100.0% and a specificity of 67.3%； for the liver-kidney Yin-deficiency syndrome， the single PLR model had an AUC of 0.842 （95% CI 0.731-0.952， P<0.01）， with a sensitivity of 83.3% and a specificity of 84.0%. ConclusionUrate crystal deposition in HUA patients exhibits intimate associations with high-sugar beverage consumption as well as elevated NLR and PLR levels. Meanwhile， TCM syndrome differentiation has potential correlation with inflammatory characteristics. The inflammatory indicator-based prediction model constructed based on TCM syndromes exhibits good predictive value.

ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption （HSCD） on chronic gouty arthritis （CGA） rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated， using the random number table， to a normal group （n=8） and a model group （n =33）. CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate （250 mg·kg^-1·d^-1） and hypoxanthine （300 mg·kg^-1·d^-1）， combined with intra-articular injection of a monosodium urate （MSU） crystal suspension （50 μL， 25 g·L^-¹） into the left ankle twice weekly. After 4 weeks of modeling， 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group， an HSCD group （10.35 g·kg^-1·d^-1， gavage once daily）， an M1 polarization agonist group （L-methionine sulfoximine， 300 mg·kg^-1， subcutaneous injection every other day）， an M1 polarization agonist + HSCD group， an M2 polarization inhibitor group （PD0325901， 10 mg·kg^-1·d^-1， gavage once daily）， and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment， whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium （CMC-Na） vehicle （10.35 g·kg^-1·d^-1， gavage once daily）. All interventions were continued for four weeks. During the intervention period， except for the normal group， potassium oxonate （250 mg·kg⁻¹） and hypoxanthine （300 mg·kg^-1） were co-administered by gavage every other day to maintain the model. At the end of treatment， serum uric acid （SUA）， ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， chemokine C-C motif ligand 2 （CCL2）， S100 calcium-binding protein A8/A9 （S100A8/A9）， interleukin-10 （IL-10） and arginase-1 （Arg-1） in serum and joint fluid were determined by enzyme-linked immunosorbent assay （ELISA）. High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin （HE） staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase （iNOS） and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 （CD163） in synovial tissue. ResultsCompared with the normal group， the model group showed significantly elevated SUA level and joint swelling index， and increased levels of pro-inflammatory cytokines， CCL2， and S100A8/A9 in both serum and joint fluid （P<0.05）， accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated （P<0.05）. Compared with model group， rats in HSCD group had significantly lower SUA levels， attenuated joint swelling， reduced serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid， accompanied with alleviated MSU deposition and synovial inflammation （P<0.05）. HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS （P<0.05）， whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group， the M1 polarization agonist + HSCD group showed significantly reduced joint swelling， lower serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in joint fluid （P<0.05）. In addition， synovial inflammatory cell infiltration and angiogenesis were attenuated， and iNOS mRNA and protein expression levels were significantly reduced （P<0.05）. Compared with the M2 polarization inhibitor group， the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling， decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation （P<0.05）， whereas the levels of anti-inflammatory mediators （IL-10， Arg-1） and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats， at least in part， by inhibiting macrophage polarization toward the M1 phenotype.

ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules， reveal the quality fluctuation patterns of products from the same and different manufacturers， providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector（HPLC-DAD-CAD） was employed to determine the contents of 4 components（syringic acid， leonurine hydrochloride， ferulic acid， and stachydrine hydrochloride） in samples from 19 manufacturers（53 batches， 159 boxes）. Additionally， fingerprint profiles were constructed， and the fingerprint dissimilarity（P_S） and relative standard deviation（RSD） of different samples from the same manufacturer were calculated. A principal component analysis（PCA） model was established with P_S and the RSD values of the 4 components as variables to classify the manufacturers. Finally， samples from 5 manufacturers（M1-M5） covering three consistency groups were selected to calculate three quality consistency parameters， namely intra-batch consistency（P_A）， inter-batch consistency（P_B）， and P_S. Then， PCA was performed with P_A， P_B， and P_S of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them， the content of stachydrine hydrochloride（a pharmacopoeial quality control component） was 32.46-72.70 mg per bag， all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China， with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows：syringic acid of 1.43-41.92 mg per bag， leonurine hydrochloride of 0.67-11.85 mg per bag， and ferulic acid of 0.11-3.81 mg per bag. Notably， leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer（RSD of 4.8%-59.2%）. PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers（M2， M6， M7， M8， M10， M15， M17， M18） demonstrated relatively high consistency， five manufacturers（M3， M9， M12， M13， M14） showed moderate consistency， six manufacturers（M1， M4， M5， M11， M16， M19） exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers， verifying the reliability of the proposed method. Among these， manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories， and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.

ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules， reveal the quality fluctuation patterns of products from the same and different manufacturers， providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector（HPLC-DAD-CAD） was employed to determine the contents of 4 components（syringic acid， leonurine hydrochloride， ferulic acid， and stachydrine hydrochloride） in samples from 19 manufacturers（53 batches， 159 boxes）. Additionally， fingerprint profiles were constructed， and the fingerprint dissimilarity（P_S） and relative standard deviation（RSD） of different samples from the same manufacturer were calculated. A principal component analysis（PCA） model was established with P_S and the RSD values of the 4 components as variables to classify the manufacturers. Finally， samples from 5 manufacturers（M1-M5） covering three consistency groups were selected to calculate three quality consistency parameters， namely intra-batch consistency（P_A）， inter-batch consistency（P_B）， and P_S. Then， PCA was performed with P_A， P_B， and P_S of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them， the content of stachydrine hydrochloride（a pharmacopoeial quality control component） was 32.46-72.70 mg per bag， all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China， with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows：syringic acid of 1.43-41.92 mg per bag， leonurine hydrochloride of 0.67-11.85 mg per bag， and ferulic acid of 0.11-3.81 mg per bag. Notably， leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer（RSD of 4.8%-59.2%）. PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers（M2， M6， M7， M8， M10， M15， M17， M18） demonstrated relatively high consistency， five manufacturers（M3， M9， M12， M13， M14） showed moderate consistency， six manufacturers（M1， M4， M5， M11， M16， M19） exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers， verifying the reliability of the proposed method. Among these， manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories， and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.

Objective: To explore the association between the HLA antibody positivity rate in female blood donors and pregnancy history, number of pregnancies, interval from the last pregnancy to blood donation, and age, to identify associated variables using a univariate generalized additive model (GAM), and to further analyze the predictive role of characteristic variables for HLA antibody positivity using a random forest model. Methods: HLA antibody detection was performed on 391 female blood donors using the Luminex immunomagnetic bead method. The correlation between pregnancy-related factors and HLA antibodies was analyzed using the Chi-square test. Based on R software, a univariate GAM was first constructed to analyze the association types between characteristic variables and the HLA antibody positivity rate, followed by the construction of a random forest model to evaluate the predictive value of the variables. Results: Among the 391 female blood donors without a transfusion history, the overall HLA antibody positivity rate was 26.34%. The positivity rate in donors with a pregnancy history was significantly higher than that in those without (30.09% vs 9.72%, P<0.05), and HLA antibody positivity rate increased linearly with the number of pregnancies (P<0.05). In the univariate GAM, age and number of deliveries exhibited a non-linear association with the HLA antibody positivity rate (the positivity rate increased sharply between 25-35 years of age and stabilized after 3 deliveries). Besides, the interval from the last pregnancy to blood donation showed a linear association with the HLA antibody positivity rate, and the positivity rate decreased as the interval prolonged (P<0.05). In the random forest model, age (mean decrease gini=29.26) and interval from the last pregnancy to blood donation (mean decrease gini=22.02) were core predictive variables: age was more conducive to identifying positive samples, while the interval from the last pregnancy to blood donation was more helpful for excluding negative samples. The number of deliveries (mean decrease accuracy=16.98) made a significant contribution to predicting positive samples, whereas the number of abortions had no impact. The model had an AUC of 0.583 (95% CI: 0.593 8-0.770 2), indicating a certain predictive value. Conclusion: The associated variables identified by the univariate GAM model, including age, interval from the last pregnancy to blood donation, and number of deliveries, provide a basis for key variables in the random forest model. All three variables have predictive value for HLA antibody positivity, which can provide evidence-based support for personalized transfusion management and stratified screening of female blood donors in this region.

OBJECTIVE To evaluate the cost-effectiveness of zolbetuximab combined with chemotherapy as first-line treatment for CLDN18.2-positive and HER2-negative advanced gastric cancer from the perspective of China’s healthcare system. METHODS Based on individual data from the GLOW clinical trial involving CLDN18.2-positive and HER2-negative patients with advanced gastric cancer， a comparison was made between the zolbetuximab combined with chemotherapy regimen and the chemotherapy alone regimen. A dynamic Markov model was employed for simulation， with a cycle length of 21 days and a time horizon of ten years. A cost-utility analysis was employed， with both costs and health outcomes discounted at an annual rate of 5%. The primary outcome measures included total cost， quality-adjusted life years （QALY） and incremental cost-effectiveness ratio （ICER）， with the willingness-to-pay （WTP） threshold set at three times China’s per capita gross domestic product in 2024 （287 247 yuan/QALY）. One-way analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Furthermore， scenario analysis and threshold analysis were conducted to explore the impact of drug price adjustments on cost-effectiveness and the threshold price. RESULTS Compared with the chemotherapy alone regimen， the ICER of zolbetuximab combined with chemotherapy was 2 611 943.00 yuan/QALY. One-way sensitivity analysis indicated that the utility value of the progression free survival， the cost of zolbetuximab and body surface area were the three most influential parameters affecting the ICER. The results of the probabilistic sensitivity analysis showed that when the WTP threshold was set at 2 617 450 yuan/QALY， the probability that the combined regimen was cost-effective approached 50%. Scenario analysis revealed that only when the price of zolbetuximab was reduced to 10% of the baseline price did the ICER of the combined regimen fall below the aforementioned WTP threshold. Threshold analysis further indicated that when the unit price of zolbetuximab dropped to 3.81 yuan/mg， the probability of the combination regimen being cost-effective was approximately 50%. CONCLUSIONS From the perspective of China’s healthcare system， zolbetuximab combined with chemotherapy regimen as first-line treatment for CLDN18.2-positive and HER2-negative advanced gastric cancer is not cost-effective compared with chemotherapy alone regimen. When the unit price of zolbetuximab drops to 3.81 yuan/mg or below， the regimen becomes cost-effective.

Objective To systematically evaluate the risk prediction models for anastomotic leakage (AL) in patients with esophageal cancer after surgery. Methods A computer-based search of PubMed, EMbase, Web of Science, Cochrane Library, Chinese Medical Journal Full-text Database, VIP, Wanfang, SinoMed and CNKI was conducted to collect studies on postoperative AL risk prediction model for esophageal cancer from their inception to October 1st, 2023. PROBAST tool was employed to evaluate the bias risk and applicability of the model, and Stata 15 software was utilized for meta-analysis. Results A total of 19 literatures were included covering 25 AL risk prediction models and 7373 patients. The area under the receiver operating characteristic curve (AUC) was 0.670-0.960. Among them, 23 prediction models had a good prediction performance (AUC>0.7); 13 models were tested for calibration of the model; 1 model was externally validated, and 10 models were internally validated. Meta-analysis showed that hypoproteinemia (OR=9.362), postoperative pulmonary complications (OR=7.427), poor incision healing (OR=5.330), anastomosis type (OR=2.965), preoperative history of thoracoabdominal surgery (OR=3.181), preoperative diabetes mellitus (OR=2.445), preoperative cardiovascular disease (OR=3.260), preoperative neoadjuvant therapy (OR=2.977), preoperative respiratory disease (OR=4.744), surgery method (OR=4.312), American Society of Anesthesiologists score (OR=2.424) were predictors for AL after esophageal cancer surgery. Conclusion At present, the prediction model of AL risk in patients with esophageal cancer after surgery is in the development stage, and the overall research quality needs to be improved.

“Runner’s high” refers to a momentary sense of pleasure that suddenly appears during running or other exercise activities, characterized by anti-anxiety, pain relief, and other symptoms. The neurobiological mechanism of “runner’s high” is unclear. This review summarizes human and animal models for studying “runner’s high”, analyzes the neurotransmitters and neural circuits involved in runner’s high, and elucidates the evidence and shortcomings of researches related to “runner’s high”. This review also provides prospects for future research. Research has found that exercise lasting more than 30 min and with an intensity exceeding 70% of the maximum heart rate can reach a “runner’s high”. Human experiments on “runner’s high” mostly use treadmill exercise intervention, and evaluate it through questionnaire surveys, measurement of plasma AEA, miRNA and other indicators. Animal experiments often use voluntary wheel running intervention, and evaluate it through behavioral experiments such as conditional place preference, light dark box experiments (anxiety), hot plate experiments (pain sensitivity), and measurement of plasma AEA and other indicators. Dopamine, endogenous opioid peptides, endogenous cannabinoids, brain-derived neurotrophic factor, and other substances increase after exercise, which may be related to the “runner’s high”. However, attention should be paid to the functional differences of these substances in the central and peripheral regions, as well as in different brain regions. Moreover, current studies have not identified the targets of the neurotransmitters or neural factors mentioned above, and further in-depth researches are needed. The mesolimbic dopamine system, prefrontal cortex-nucleus accumbens projection, ventral hippocampus-nucleus accumbens projection, red nucleus-ventral tegmental area projection, cerebellar-ventral tegmental area projection, and brain-gut axis may be involved in the regulation of runner’s high, but there is a lack of direct evidence to prove their involvement. There are still many issues that need to be addressed in the research on the neurobiological mechanisms of “runner’s high”. (1) Most studies on “runner’s high” involve one-time exercise, and the characteristics of changes in “runner’s high” during long-term exercise still need to be explored. (2) The using of scales to evaluate subjects lead to the lacking of objective indicators. However, some potential biomarkers (such as endocannabinoids) have inconsistent characteristics of changes after one-time and long-term exercise. (3) The neurotransmitters involved in the formation of the “runner’s high” all increase in the peripheral and/or central nervous system after exercise. Attention should be paid to whether peripheral substances can enter the blood-brain barrier and the binding effects of neurotransmitters to different receptors are completely different in different brain regions. (4) Most of the current evidence show that some brain regions are activated after exercise. Is there a functional circuit mediating “runner’s high” between these brain regions? (5) Although training at a specific exercise intensity can lead to “runner’s high”, most runners have not experienced “runner’s high”. Can more scientific training methods or technological means be used to make it easier for people to experience the “runner’s high” and thus be more willing to engage in exercise? (6) The “runner’s high” and “addiction” behaviors are extremely similar, and there are evidences that exercise can reverse addictive behaviors. However, why is there still a considerable number of people in the sports population and even athletes who smoke or use addictive drugs instead of pursuing the “pleasure” brought by exercise? Solving the problems above is of great significance for enhancing the desire of exercise, improving the clinical application of neurological and psychiatric diseases through exercise, and enhancing the overall physical fitness of the population.