Based on the theory of "disease of both blood and water" in Essentials from the Golden Cabinet （《金匮要略》）， and in combination with the dynamic syndrome evolution of heart failure with preserved ejection fraction （HFpEF）， this paper systematically clarifies the pathomechanism of HFpEF， characterized by yang deficiency as the root， blood stasis as the pivotal factor and water retention as the manifestation. Accordingly， the therapeutic principles have been proposed， which are warming yang and banking up original qi to consolidate the root， activating blood and unblocking collaterals to smooth the mechanism， and promoting urination and regulating pivot to remove the branch. On this basis， a compound formula structure of "one monarch， one minister and one assistant" is established， forming an integrated intervention strategy that synergistically combines the three methods of warming yang， activating blood， and promoting urination through combined classical formulas. Zhenwu Decoction （真武汤）， which warms yang and dissolves rheum， is used to consolidate the root and directly target the source of yang deficiency， serving as the monarch； Guizhi Fuling Pills （桂枝茯苓丸）， which activates blood， promotes urination and unblocks the pivot， assists in interrupting the binding of blood stasis and water retention， serving as the minister； Tingli Dazao Xiefei Decoction （葶苈大枣泻肺汤）， which regulates qi， disperses retained fluids， and eliminates the manifestation， alleviates acute water-retention symptoms， serving as the assistant. This compound formula is warming without being drying， diuretic without being drastic， and dispels stasis without consuming blood， thereby achieving the therapeutic effects of warming yang， activating blood， and promoting urination.

OBJECTIVE To analyze the selection and rationales of comparators for pharmaceutical enterprises in their medical insurance access application， so as to provide a reference for promoting communication and consensus between enterprises and medical insurance authorities in this process. METHODS The application materials for drugs outside the catalogue that passed formal review published by the National Healthcare Security Administration from 2021 to 2025 were extracted， and then content analysis was used to systematically sort out relevant information of the declared drugs and comparators； the specific situations and rationales of pharmaceutical enterprises’ selection of comparators were analyzed. RESULTS A total of 1 341 declared drug documents were collected. Data analysis showed that 1 035 （77.18%） were submitted with positive comparators and 306 （22.82%） used blank comparators； 58 drugs （4.33%） took combination therapy as the reference， and 5 drugs （0.37%） referred to non-pharmacological （or non-single pharmacological） treatment regimens. Among competitive drugs declared by multiple enterprises， 50.00% of the enterprises submitted different comparators. A total of 4 basic conditions and 39 additional conditions were extracted as the rationales for selecting positive comparators. For blank comparators， 12 drug-related factors， 2 administrative factors， and 1 other factor were identified. More than 10% of the drugs did not state the rationale for comparator selection， and over 44% of drugs using blank comparators provided only one justification. CONCLUSIONS Pharmaceutical enterprises mainly select comparators based on their own interests in the medical insurance access application， and there are deficiencies in the adequacy and standardization of their selection basis and reasoning. It is recommended that enterprises follow the principled requirements of medical insurance authorities， and fully and normatively explain the reasons for selecting comparators in combination with the characteristics of their own products. Meanwhile， it is advisable to change the current open-ended statement form of selection reasons into a closed-ended answering mode， so as to highlight the priority of selection， standardize the declaration behavior of enterprises， and reduce communication divergences between the two parties.

Type 2 diabetes mellitus （T2DM） and hypertension are common and frequent chronic non-communicable diseases， which often coexist in clinical practice， resulting in a large number of cardiovascular events and deaths， and their case fatality rate far exceeds that of other factors such as dyslipidemia and obesity. Based on the diagnostic standards， guidelines， and animal model evaluation methods of T2DM with hypertension at home and abroad， this study summarized， evaluated， and analyzed the characteristics of the existing animal models of T2DM with hypertension based on the clinical symptoms in traditional Chinese and Western medicine. The animal models showing high fitting degrees with the clinical symptoms in Western medicine are mainly established by injection of streptozocin （STZ） in SHR rats in the surgical induction and chemical induction methods and feeding a high-fat and high-salt diet combined with STZ injection in SD rats in the dietary induction methods. The models showcasing high fitting degrees with the clinical symptoms in traditional Chinese medicine （TCM） are mainly established by the surgical induction method. Considering the fitting degrees and the advantages and disadvantages， the ideal modeling method for T2DM with hypertension is the two-kidney， one clip （2K1C） method （a surgical induction method） combined with feeding a high-fat and high-sugar diet and STZ injection. However， the available models lack the characteristics of TCM and the evaluation indicators have poor specificity. This study found that there are few animal models of T2DM with hypertension considering the characteristics of both disease and syndrome， which may be related to the identification and attribution of TCM syndromes in animal macroscopic information. In view of this problem， it is suggested that the evaluation criteria should be established and improved for the animal models combining disease and syndrome， which can help to evaluate the fitting degree of the pathological characteristics of different syndromes in the animal models of T2DM with hypertension. In this way， ideal animal models of T2DM with hypertension can be established to simulate the disease occurrence and development in the human body. The animal models are expected to provide an ideal approach for the further research on the pathogenesis of T2DM and its prevention and treatment with TCM， which is of great significance for the treatment and prevention of T2DM with hypertension and the prognosis of its complications. At the same time， breakthroughs in the basic syndrome models of comorbidities are expected to lay a foundation for the leapfrog development of TCM research.

Type 2 diabetes mellitus （T2DM） and hypertension are common and frequent chronic non-communicable diseases， which often coexist in clinical practice， resulting in a large number of cardiovascular events and deaths， and their case fatality rate far exceeds that of other factors such as dyslipidemia and obesity. Based on the diagnostic standards， guidelines， and animal model evaluation methods of T2DM with hypertension at home and abroad， this study summarized， evaluated， and analyzed the characteristics of the existing animal models of T2DM with hypertension based on the clinical symptoms in traditional Chinese and Western medicine. The animal models showing high fitting degrees with the clinical symptoms in Western medicine are mainly established by injection of streptozocin （STZ） in SHR rats in the surgical induction and chemical induction methods and feeding a high-fat and high-salt diet combined with STZ injection in SD rats in the dietary induction methods. The models showcasing high fitting degrees with the clinical symptoms in traditional Chinese medicine （TCM） are mainly established by the surgical induction method. Considering the fitting degrees and the advantages and disadvantages， the ideal modeling method for T2DM with hypertension is the two-kidney， one clip （2K1C） method （a surgical induction method） combined with feeding a high-fat and high-sugar diet and STZ injection. However， the available models lack the characteristics of TCM and the evaluation indicators have poor specificity. This study found that there are few animal models of T2DM with hypertension considering the characteristics of both disease and syndrome， which may be related to the identification and attribution of TCM syndromes in animal macroscopic information. In view of this problem， it is suggested that the evaluation criteria should be established and improved for the animal models combining disease and syndrome， which can help to evaluate the fitting degree of the pathological characteristics of different syndromes in the animal models of T2DM with hypertension. In this way， ideal animal models of T2DM with hypertension can be established to simulate the disease occurrence and development in the human body. The animal models are expected to provide an ideal approach for the further research on the pathogenesis of T2DM and its prevention and treatment with TCM， which is of great significance for the treatment and prevention of T2DM with hypertension and the prognosis of its complications. At the same time， breakthroughs in the basic syndrome models of comorbidities are expected to lay a foundation for the leapfrog development of TCM research.

Severe pneumonia is one of the most common and critical respiratory diseases in clinical practice. It is characterized by rapid progression， difficult treatment， high mortality， and many complications， posing a significant threat to the life and health of patients. The pathogenesis of severe pneumonia is highly complex， and studies have shown that its occurrence and development are closely related to multiple signaling pathways. Currently， the treatment of severe pneumonia mainly focuses on anti-infection， mechanical ventilation， and glucocorticoids， but clinical outcomes are often not ideal. Therefore， finding safe and effective alternative therapies is particularly important. In recent years， with the deepening of research into traditional Chinese medicine （TCM）， it has gained widespread attention in the treatment of severe pneumonia. This paper reviewed the relationship between severe pneumonia and relevant signaling pathways in recent years and how TCM regulated these pathways in the treatment of severe pneumonia. It was found that TCM could regulate the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， NOD-like receptor protein 3 （NLRP3）， and nuclear factor E₂-related factor 2 （Nrf2） signaling pathways， playing a role in reducing the inflammatory response， inhibiting cell apoptosis and pyroptosis， improving oxidative stress， and other effects in the treatment of severe pneumonia. Among these pathways， it was found that all of them regulated inflammation to treat severe pneumonia. Therefore， reducing inflammation is the core mechanism by which Chinese medicine treats severe pneumonia. This review provides direction for the clinical treatment of severe pneumonia and offers a scientific basis for the research and development of new drugs.

The rupture of carotid vulnerable plaques is the core pathological basis for major cardiovascular and cerebrovascular events. However， the insufficient alignment between existing animal models and the clinical disease and syndrome characteristics of traditional Chinese and western medicine has limited research progress. In this study， biomedical databases in China and abroad were systematically searched， and the modeling mechanisms and evaluation systems of carotid vulnerable plaque animal models were systematically assessed based on diagnostic criteria of both traditional Chinese and western medicine. Analysis of the clinical correspondence indicated that existing animal models can be categorized into four types： simple high-fat diet， surgical induction combined with high-fat feeding， genetic engineering combined with high-fat feeding， and drug induction combined with high-fat feeding. Among these， the compound strategy of surgical induction combined with high-fat feeding has become the current mainstream approach， showing good concordance with western medicine. The study found that the double balloon injury rabbit model and the ApoE^-/- mouse carotid artery tandem constriction combined with high-fat feeding model demonstrated a high degree of clinical correspondence with both traditional Chinese and western medicine in terms of vulnerable plaque imaging and pathological features. Nevertheless， existing models still face significant technical limitations in faithfully simulating plaque pathology and in translating findings to clinical applications. To address these challenges， integrating complex comorbidity mechanism construction， multimodal dynamic mechanism monitoring， and collaborative evaluation systems of traditional Chinese and western medicine could enable the development of highly concordant carotid vulnerable plaque disease-syndrome combination animal models. Such models would provide a reproducible experimental platform for targeted drug development to regulate plaque stability and for individualized precision treatment， as well as a theoretical basis for innovation in clinical diagnostic and therapeutic strategies.

ObjectiveTo investigate the possible mechanism of Bushen Huoxue Granule （补肾活血颗粒， BHG） in treating Parkinson's disease （PD） from the perspecitve of dopamine （DA） homeostasis. MethodsSeventy-two mice were randomly divided into blank group， model group， madopar group and BHG low-， medium- and high-dose groups， with 12 mice in each group. Except for the blank group， all mice were administered intraperitoneal injections of 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） for 7 consecutive days to induce a PD model. On the day following the injection， BHG low-， medium- and high-dose groups were administered BHG at doses of 1.25， 2.5， and 5.0 mg/（g·d） by oral gavage， respectively， while the madopar group received madopar tablets at dose of 0.093 8 mg/（g·d） by oral gavage. The blank group and the model group were given 0.2 ml/10 g of distilled water by gavage. All treatments were given once daily for 14 days. Open field test， pole climbing test and grip test were used to evaluate the behavior of mice in each group. Immunohistochemistry was used to detect the expression of tyrosine hydroxylase （TH） in striatum. Nissl staining was used to detect the activity of striatal neurons. The contents of DA and 3,4-dihydroxyphenylacetic acid （DOPAC） in striatum were detected by ultra performance liquid chromatography tandem mass spectrometry. The number and volume of synaptic vesicles were observed by transmission electron microscope. The expression of vesicular monoamine transporter 2 （VMAT2） in striatum was detected by immunofluorescence. Western Blot was used to detect the expression of extracellular signal-regulated kinase （ERK）， phosphorylated ERK （p-ERK）， cAMP response element-binding protein （CREB）， phosphorylated CREB （p-CREB） and VMAT2 in striatum. ResultsCompared to the blank group， mice in the model group showed a significant decline in total distance and average speed in the open field test， along with an increase in total resting time； in the pole test， both the time required for the mice to turn completely downward （T-turn） and the total time taken to reach the bottom of the pole （T-total） were prolonged； forelimb grip strength was reduced； in the striatum， the mean optical density of TH， the average fluorescence intensity of VMAT2 protein， and DA content all decreased， while the number of striatal neurons was reduced， and the DOPAC/DA ratio was elevated； the levels of p-ERK/ERK， p-CREB/CREB， and VMAT2 in the striatum significantly decreased （P＜0.01）； transmission electron microscopy revealed that both the number and volume of synaptic vesicles in striatal neurons were markedly reduced. Compared to the model group， mice in the madopar group and BHG low-， medium- and high-dose groups showed significant improvements in all the above indicators （P＜0.05 or P＜0.01）. Compared to madopar group， the BHG high-dose group exhibited increased DA content and elevated p-CREB/CREB ratio in the striatum （P＜0.05）. Compared to the BHG low-dose group， the BHG high-dose group showed increased total distance and mean velocity， decreased total resting time， T-turn， and T-total， as well as enhanced forelimb grip strength； moreover， the average fluorescence intensity of VMAT2 protein， DA content， p-ERK/ERK， p-CREB/CREB， and VMAT2 levels in the striatum were all significantly elevated （P＜0.05 or P＜0.01）. ConclusionBHG may restore DA homeostasis and alleviate the damage of dopaminergic neurons by regulating ERK/CREB/VMAT2 signaling pathway.

Objective:To evaluate the value of a combined model based on primary lesion 18F-fluorodeoxyglucose ( 18F-FDG) PET/CT radiomics for predicting lymph node metastasis in non-small cell lung cancer (NSCLC) . Methods:A retrospective analysis was conducted on the clinical data of 203 NSCLC patients who underwent pre-treatment PET/CT imaging at Nanjing Drum Tower Hospital from June 2013 to July 2023. Patients were randomly assigned to the training set ( n=142) and the validation set ( n=61) at a ratio of 7∶3. A predictive model was developed in the training set, and its predictive performance and clinical application value were assessed in both the training and validation sets. Traditional PET/CT parameters and PET/CT radiomics features of the primary lesion were obtained by 3D-slicer software. Least absolute shrinkage and selection operator (LASSO), random forest, and extreme gradient boosting were performed to extract features. Support vector machine was used to construct a radiomics score (Radscore). Univariate and multivariate logistic regression analysis was used to predict the influencing factors of lymph node metastasis in NSCLC patients and to establish models. Predictive performance of the models was evaluated by receiver operator characteristic (ROC) curves and clinical application value was assessed by calibration curves and decision curve analysis (DCA) . Results:Among 203 NSCLC patients, 116 had lymph node metastasis, with 64 cases in the training set and 52 cases in the validation set. Three complementary classical machine learning methods were used for feature screening, and finally 10 radiomics features were obtained. The optimal threshold for Radscore-PET was 0.43 and the optimal threshold for Radscore-CT was 0.39. Univariate analysis showed that, sex ( OR=0.48, 95% CI: 0.24-0.95, P=0.036), tumor marker levels ( OR=3.81, 95% CI: 1.84-7.91, P<0.001), long diameter of tumor ( OR=2.56, 95% CI: 1.27-5.16, P=0.009), short diameter of tumor ( OR=3.73, 95% CI: 1.75-7.92, P=0.001), vacuolar sign ( OR=0.32, 95% CI: 0.12-0.86, P=0.024), ring-like metabolism ( OR=3.67, 95% CI: 1.33-10.13, P=0.012), maximum standardized uptake value (SUV max) ( OR=6.57, 95% CI: 3.03-14.25, P<0.001), metabolic tumor volume (MTV) ( OR=2.91, 95% CI: 1.43-5.92, P=0.003), total lesion glycolysis (TLG) ( OR=4.23, 95% CI: 2.08-8.59, P<0.001), Radscore-PET ( OR=21.93, 95% CI: 9.04-53.20, P<0.001) and Radscore-CT ( OR=13.72, 95% CI: 6.12-30.76, P<0.001) were all influencing factors for predicting lymph node metastasis in NSCLC patients. Multivariate analysis showed that, tumor marker levels ( OR=2.55, 95% CI: 1.11-5.90, P=0.028), vacuolar sign ( OR=0.26, 95% CI: 0.08-0.83, P=0.023), SUV max ( OR=5.94, 95% CI: 1.99-17.75, P=0.001), Radscore-PET ( OR=25.51, 95% CI: 5.92-110.22, P<0.001), and Radscore-CT ( OR=8.68, 95% CI: 2.73-27.61, P<0.001) were independent influencing factors for predicting lymph node metastasis in patients with NSCLC. Based on the above independent influencing factors, models were constructed: the traditional model (tumor marker levels, vacuolar sign, SUV max), the PET model (SUV max, Radscore-PET), the CT model (vacuolar sign, Radscore-CT), and the combined model (tumor marker levels, vacuolar sign, SUV max, Radscore-PET, Radscore-CT). ROC curve analysis showed that, the area under curve (AUC) of the traditional, PET, CT, and combined models in the training set were 0.75 (95% CI: 0.67-0.82), 0.90 (95% CI: 0.84-0.95), 0.85 (95% CI: 0.78-0.90), and 0.94 (95% CI: 0.88-0.97), respectively. The predictive value of the combined model was higher than that of the traditional model ( Z=5.01, P<0.001), the PET model ( Z=1.99, P=0.047), and the CT model ( Z=3.25, P=0.001). In the validation set, the AUCs for the traditional model, PET model, CT model, and combined model were 0.65 (95% CI: 0.52-0.77), 0.86 (95% CI: 0.74-0.93), 0.85 (95% CI: 0.73-0.93), and 0.90 (95% CI: 0.80-0.96), respectively. The predictive value of the combined model was superior to that of the traditional model ( Z=3.23, P=0.001). The sensitivity and specificity of the combined model in the training set were 84.37% and 91.03%, while in the validation set, the sensitivity and specificity were 82.61% and 94.74%, respectively. Calibration curves showed a good agreement between the predicted and actual probabilities in both the training and validation sets. DCA showed that the combined models had good discriminative ability in both the training and validation sets. Conclusions:Tumor marker levels, vacuolar sign, SUV max, Radscore-PET, and Radscore-CT are all independent influencing factors for predicting lymph node metastasis in patients with NSCLC. The combined model based on these factors demonstrates excellent predictive performance and clinical application value for predicting lymph node metastasis in NSCLC.

Objective:To evaluate the prognostic value of 18F-fluorodeoxyglucose ( 18F-FDG) PET/CT metabolic parameters in small cell lung cancer (SCLC) . Methods:A retrospective analysis was conducted on the clinical and imaging data of 156 SCLC patients, who underwent 18F-FDG PET/CT imaging and were diagnosed by histopathological examination at Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from September 2013 to February 2024. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), linear regression slope, area under the curve of cumulative standard uptake value (SUV) volume histogram (AUC-CSH), and coefficient of variation (CV) were calculated using LIFEx software with different SUV thresholds. Univariate and multivariate analyses were performed using Cox proportional hazards model. Patient stratification was based on the critical values determined by receiver operator characteristic (ROC) curve analysis. The survival curve was plotted using the Kaplan-Meier method and log-rank test was performed. Results:Univariate analysis showed that MTV 40% ( HR=2.91, 95% CI: 1.55-5.47, P=0.001), MTV 60% ( HR=2.31, 95% CI: 1.29-4.17, P=0.005), TLG 40% ( HR=2.07, 95% CI: 1.19-3.60, P=0.010), linear regression slope ( HR=0.45, 95% CI: 0.26-0.79, P=0.005), and CV 40% ( HR=0.27, 95% CI: 0.08-0.84, P=0.024) were factors affecting progression-free survival (PFS) in SCLC patients. MTV 40% ( HR=1.98, 95% CI: 1.22-3.22, P=0.005), MTV 60% ( HR=1.80, 95% CI: 1.12-2.88, P=0.015), MTV 80% ( HR=1.71, 95% CI: 1.08-2.74, P=0.024), TLG 40% ( HR=3.68, 95% CI: 1.59-8.49, P=0.002), linear regression slope ( HR=0.49, 95% CI: 0.30-0.80, P=0.004), and AUC-CSH 80% ( HR=0.44, 95% CI: 0.23-0.84, P=0.013) were found to be factors affecting overall survival (OS) in SCLC patients. Multivariate analysis revealed that MTV 40% ( HR=4.76, 95% CI: 1.11-20.50, P=0.036) was an independent factor influencing PFS, and TLG 40% ( HR=3.19, 95% CI: 1.02-9.92, P=0.046) was an independent factor influencing OS in SCLC patients. ROC curve analysis identified the optimal cutoff value for MTV 40% in predicting PFS as 5.5cm 3 and the optimal cutoff value for TLG 40% in predicting OS as 41.5 g in SCLC patients. Survival analysis showed that patients with MTV 40%≤5.5 cm 3 ( n=33) had a median PFS that was not reached, while patients with MTV 40%>5.5 cm 3 ( n=123) had a median PFS of 10.3 months, with a statistically significant difference ( χ2=12.09, P=0.001). For patients with TLG 40%≤41.5 g ( n=35), the median OS was not reached, whereas for TLG 40%>41.5 g ( n=121), the median OS was 31.6 months, with a statistically significant difference ( χ2=10.55, P=0.001) . Conclusions:The 18F-FDG PET/CT metabolic parameter MTV 40% is an independent factor influencing PFS, while TLG 40% is an independent factor influencing OS in SCLC patients. The above two parameters may serve as indicators for assessing the prognosis of SCLC patients.

Tonifying herbs described in the Shen Nong Ben Cao Jing frequently possess well-defined efficacy in dispelling pathogenic factors, including eliminating pathogenic factors, eliminating severe wind-disorders, dispelling Bi syndrome, removing blood stasis and resolving hard masses, facilitating urination and defecation, relieving chills and fever, promoting digestion, regulating and smoothing qi movement, treating carbuncles and deep-rooted ulcers, killing the :three worms: (parasites), draining pus and alleviating pain, and treating bone fractures and traumatic injuries. These effects correspond to a broad spectrum of conditions, encompassing immune, digestive, and respiratory system disorders, as well as tumors. These effects are closely related to the taste and compatibility of drugs, and are supported by modern pharmacological studies (such as anti-inflammatory, anti-tumor, immune regulation, etc.). This study could provide a novel perspective for the rational clinical application of tonifying herbs and establish a foundation for in-depth research into the multi-efficacy mechanisms of Chinese materia medica.