Retinal microcirculatory disorder is a key factor in the occurrence and development of diabetic retinopathy （DR）， and also an important link in the prevention and treatment of DR. The theory of "Gaozhuo" holds that the microcirculatory disorder in DR is based on the deficiency of spleen Qi and is characterized by the obstruction caused by "Gaozhuo" and blood stasis. The deficiency of spleen Qi is an essential precondition for the endogenous formation and accumulation of Gaozhuo， while Gaozhuo invasion is the direct cause of microcirculatory disorders in DR. The deficiency of spleen Qi and the endogenous formation of Gaozhuo mean the process in which glucose metabolism dysfunction induces an excessive production of inflammatory factors and lipid metabolites. The obstruction caused by "Gaozhuo" and blood stasis is the direct pathogenesis of microcirculatory disorders in DR， encompassing two stages： Gaozhuo obstruction and turbidity and stasis stagnation. Gaozhuo obstruction and turbidity and stasis stagnation represent the process in which inflammatory factors and lipid metabolites damage the retinal microcirculation and induce thrombosis， thus mediating microcirculatory disorders. Turbidity and stasis stagnation and blood extravasation outside the vessels reveal the progression to microvascular rupture and hemorrhage resulting from the microcirculatory disorders. According to the pathogenesis evolution of the theory of "Gaozhuo"， microcirculatory disorders in DR can be divided into deficiency of spleen Qi with Gaozhuo obstruction， deficiency of spleen Qi with turbidity and stasis stagnation， and turbidity and stasis stagnation with blood extravasation outside the vessels. Clinically， treatment principles should focus on strengthening the spleen and benefiting Qi， resolving turbidity， and dispersing stasis. Different syndrome patterns should be addressed with tailored therapies， such as enhancing the spleen and benefiting Qi while regulating Qi and reducing turbidity， strengthening the spleen and benefiting Qi while resolving turbidity and dispelling stasis， and strengthening the spleen and resolving turbidity while removing stasis and stopping bleeding. Representative prescriptions include modified Wendantang， modified Buyang Huanwutang， modified Danggui Buxuetang， Zhuixue Mingmu decoction， Tangmuqing， Shengqing Jiangzhuo Tongluo Mingmu prescription， Danhong Huayu decoction， and Yiqi Yangyin Huoxue Lishui formula.

ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method（Liu Junzitang Combined with Linggang Wuwei Jiangxintang） for treating acute exacerbations of chronic obstructive pulmonary disease （AECOPD） with increased eosinophils （EOS）. MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group （EG） or a control group （CG）. Both groups received conventional Western medicine， with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen （PaO₂） and partial pressure of carbon dioxide （PaCO₂）. The secondary efficacy indicators included the TCM symptom scores， the COPD Assessment Test （CAT） score， the Modified Medical Research Council （mMRC） Dyspnea Scale score， and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG， EG showed no significant difference in PaO₂ （P=0.773）， PaCO₂ （P=0.632） and or CAT score （P=0.336） at on day 3 but better PaO₂ （P=0.004）， PaCO₂ （P=0.008）， and CAT score （P=0.013） were significantly better at on day 7. Compared with CGAfter treatment， EG had lower TCM syndrome scores of than CG EG on day 3 （P=0.005） and day 7 were significantly decreased （P0.001）. There was no significant difference in mMRC score between the two groups on day 3 （P=0.514） and day 7 （P=0.176） as wasor the length of hospital stay （P=0.915）. The generalized linear mixed model （GLMM） showed that compared with CG， EG had significant improvements over time in PaO₂， PaCO₂， TCM syndrome symptom scores， CAT score， and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.

ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method（Liu Junzitang Combined with Linggang Wuwei Jiangxintang） for treating acute exacerbations of chronic obstructive pulmonary disease （AECOPD） with increased eosinophils （EOS）. MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group （EG） or a control group （CG）. Both groups received conventional Western medicine， with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen （PaO₂） and partial pressure of carbon dioxide （PaCO₂）. The secondary efficacy indicators included the TCM symptom scores， the COPD Assessment Test （CAT） score， the Modified Medical Research Council （mMRC） Dyspnea Scale score， and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG， EG showed no significant difference in PaO₂ （P=0.773）， PaCO₂ （P=0.632） and or CAT score （P=0.336） at on day 3 but better PaO₂ （P=0.004）， PaCO₂ （P=0.008）， and CAT score （P=0.013） were significantly better at on day 7. Compared with CGAfter treatment， EG had lower TCM syndrome scores of than CG EG on day 3 （P=0.005） and day 7 were significantly decreased （P0.001）. There was no significant difference in mMRC score between the two groups on day 3 （P=0.514） and day 7 （P=0.176） as wasor the length of hospital stay （P=0.915）. The generalized linear mixed model （GLMM） showed that compared with CG， EG had significant improvements over time in PaO₂， PaCO₂， TCM syndrome symptom scores， CAT score， and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.

ObjectiveTo evaluate the impact of yang-reinforcing and blood-activating therapy on the long-term prognosis for patients with dilated cardiomyopathy （DCM） of yang deficiency and blood stasis syndrome. MethodsA retrospective cohort study was conducted involving 371 DCM patients with yang deficiency and blood stasis syndrome. The yang-reinforcing and blood-activating therapy was defined as the exposure factor. Patients were categorized into exposure group （186 cases） and non-exposure group （185 cases） according to whether they received yang-reinforcing and blood-activating therapy combined with conventional western medicine for 6 months or longer. The follow-up period was set at 48 months， and the Kaplan-Meier survival analysis was used to assess the cumulative incidence of major adverse cardiovascular events （MACE） in both groups. Cox regression analysis was used to explore the impact of yang-reinforcing and blood-activating therapy on the risk of MACE， and subgroup analysis was performed. Changes in traditional Chinese medicine （TCM） syndrome score， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVEDD）， and Minnesota Living with Heart Failure Questionnaire （MLHFQ） score were compared between groups at the time of first combined use of yang-reinforcing and blood-activating therapy （before treatment） and 1 year after receiving the therapy （after treatment）. ResultsMACE occurred in 31 cases （16.67%） in the exposure group and 47 cases （25.41%） in the non-exposure group. The cumulative incidence of MACE in the exposure group was significantly lower than that in the non-exposure group ［HR=0.559， 95%CI（0.361，0.895）， P=0.014］. Cox regression analysis showed that yang-reinforcing and blood-activating therapy was an independent factor for reducing the risk of MACE in DCM patients ［HR=0.623， 95%CI（0.396，0.980）， P=0.041］， and consistent results were observed in different subgroups. Compared with pre-treatment， the exposure group showed decreased TCM syndrome score and MLHFQ score， reduced LVEDD， and increased LVEF and LVFS after treatment （P＜0.05）； in the non-exposure group， TCM syndrome score decreased， LVEF and LVFS increased， and LVEDD reduced after treatment （P＜0.05）. After treatment， the exposure group had higher LVEF and LVFS， smaller LVEDD， and lower TCM syndrome score and MLHFQ score compared with the non-exposure group （P＜0.05）. ConclusionCombining yang-reinforcing and blood-activating therapy with conventional western medicine can reduce the risk of MACE in DCM patients with yang deficiency and blood stasis syndrome， meanwhile improving their clinical symptoms， cardiac function， and quality of life.

OBJECTIVE To analyze the differences in chemical components of Gardenia jasminoides before and after processing with ginger， and to evaluate the quality differences among different producing areas. METHODS Ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry was used to analyze the compositional differences of G. jasminoides before and after processing with ginger. The water content， total ash， and ethanol-soluble extract content of ginger- processed G. jasminoides were determined according to the 2020 edition of Chinese Pharmacopoeia. High performance liquid chromatography was adopted to determine the contents of genipin gentiobioside， geniposide， crocin Ⅰ and crocin Ⅱ in ginger- processed G. jasminoides. RESULTS A total of 49 chemical components were identified from raw G. jasminoides and ginger- processed G. jasminoides， including 14 flavonoids， 15 iridoids， 10 organic acids， 2 alkaloids and 8 other compounds. Among them， 42 components were detected in raw G. jasminoides， 28 in ginger-processed G. jasminoides， and 21 components were common to both. After processing with ginger， raw G. jasminoides lost 21 components （including iridoids， flavonoids， alkaloids， and others）， while 7 chemical components were added （including coumarins， organic acids， organic acid esters， and flavonoids）. For the 15 batches of ginger-processed G. jasminoides， the water content ranged from 5.64% to 7.11%， total ash from 2.92% to 4.87%， and ethanol-soluble extract from 40.61% to 58.02%. The average contents of genipin gentiobioside， geniposide， crocin Ⅰ and crocin Ⅱ were 0.108 7， 0.542 2， 0.565 0， and 0.012 5 mg/g， respectively. CONCLUSIONS After processing with ginger， G. jasminoides loses 21 components， while 7 new components are added. Differences are observed in the water content， total ash， ethanol-soluble extract， and the contents of genipin gentiobioside， geniposide， crocin Ⅰ， and crocin Ⅱ of ginger-processed G. jasminoides from different producing areas. Notably， samples from Fujian exhibit high contents of genipin gentiobioside and ethanol-soluble extract， while samples from Jiangxi have a high content of crocin Ⅰ.

Objective To analyze the effect of the activation rate of peripheral blood monocytes on the recovery of patients after liver transplantation and to initially explore the possible influencing factors for differences in monocyte activation rates. Methods A total of 139 patients who underwent orthotopic liver transplantation from September 2020 to June 2023 at Department of Liver Surgery and Transplantation of Zhongshan Hospital, Fudan University were selected. The proportion of CD14^＋HLA-DR^＋ monocytes in peripheral blood was defined as the monocyte activation rate. The difference in monocyte activation rates between postoperative day 7 (POD7) and postoperative day 1 (POD1) was calculated as Δ, and patients were divided into Δ＞0 group (n＝73) and Δ＜0 group (n＝66). The two groups were compared in terms of complete blood count, liver and kidney function, coagulation indicators, infection indicators, ICU length of stay, total length of hospitalization, and 90-day mortality. Changes in the proportions of different monocytes subsets (Mo0, Mo1, Mo2, and Mo3) and HLA-DR expression in peripheral blood on POD1 and POD7 were detected using flow cytometry. Results The ICU length of stay in the Δ＜0 group was significantly longer than that in the Δ＞0 group (18[12, 26] days vs 14[10, 20.5] days, P＝0.018). On POD1, the proportion of Mo0 in the Δ＞0 group was significantly lower than that in the Δ＜0 group (P＜0.05); on POD7, the proportion of Mo0 in the Δ＞0 group was significantly lower than that in the Δ＜0 group (P＜0.001), while the proportions of Mo1, Mo2, and Mo3 were significantly higher than those in the Δ＜0 group (P＜0.001). Compared to POD1, the HLA-DR expression level of Mo0 in peripheral blood of patients with liver transplantation significantly decreased on POD7 (P＜0.01), while there was no significant difference in HLA-DR expression levels of Mo1, Mo2, and Mo3. Conclusions Increased proportion of Mo0 (CD14^lowCD16⁻HLA-DR^low) among peripheral blood monocyte subsets may be one of the influencing factors for the differences in monocyte activation rates in patients with liver transplantation. The difference in monocyte activation rate can serve as a new clinical indicator for assessing changes in the immune status and postoperative recovery of patients with liver transplantation.

ObjectiveTo study the effect and mechanism of Shentong Zhuyutang in treating intervertebral disc degeneration （IDD） in rats. MethodsIn the cell experiment， male rats were administrated with normal saline or low-， medium-， and high-dose （3.38， 6.75，13.5 g·kg^-1， respectively） Shentong Zhuyutang by gavage， respectively， and serum samples were collected after 7 days of continuous administration. Another 10 male rats were selected for the isolation of nucleus pulposus cells. The cell model of IDD was established by treatment with interleukin （IL）-1β. The modeled cells were then treated with Shentong Zhuyutang-containing serum and the ferroptosis inhibitor ferrostatin-1 （Fer-1）， respectively， to investigate the effects of Shentong Zhuyutang-containing serum on the proliferation and ferroptosis of nucleus pulposus cells. To study the role of silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2） in the regulation of ferroptosis in nucleus pulposus cells by Shentong Zhuyutang-containing serum， this study treated the cells with the SIRT1 inhibitor Ex 527 and the Nrf2 inhibitor ML385， respectively， in addition to the treatment with IL-1β and high-dose Shentong Zhuyutang-containing serum. The cell-counting kit-8 （CCK-8） assay and EdU staining were employed to measure the cell viability and proliferation， respectively. The Fe²⁺， glutathione （GSH）， and malondiadehyde （MDA） levels were measured by colorimetric assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， acyl-CoA synthetase long-chain family 4 （ACSL4）， Collagen Ⅱ， Aggrecan， SIRT1， and Nrf2. Immunofluorescence was used detect SIRT1 expression. In the animal experiment， male rats were treated with anulus puncture for the modeling of IDD. Rats were randomly assigned into sham operation， model， Shentong Zhuyutang-containing serum （13.5 g·kg^-1）， and positive control （nimesulide dispersible tablets， 0.18 mg·kg^-1） groups. Rats in the drug intervention groups were administrated with corresponding agents at 1 mL·kg^-1， and those in the sham operation and model groups were administrated with equal volumes of normal saline， once daily for 28 consecutive days. At the end of the last administration， the histopathological changes in the intervertebral discs of rats were observed by hematoxylin-eosin staining and scored by the Masuda method. Western blot was employed to determine the protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ in the nucleus pulposus tissue. ResultsCompared with the control group， the IL-1β group of nucleus pulposus cells showed elevated levels of Fe²⁺， MDA， and ACSL4 （P<0.05）， decreased cell viability， lowered GSH level， and down-regulated protein levels of GPX4， Collagen Ⅱ， and Aggrecan （P<0.05）. Shentong Zhuyutang-containing serum and Fer-1 reversed the effects of IL-1β on the viability and ferroptosis of nucleus pulposus cells and up-regulated the protein levels of Collagen Ⅱ and Aggrecan in nucleus pulposus cells （P<0.05）. Compared with the control group， the IL-1β group showcased down-regulated expression of Sirt1 and Nrf2 in nucleus pulposus cells （P<0.05）. Compared with the IL-1β group， the high-dose Shentong Zhuyutang-containing serum+IL-1β group showed up-regulated expression of SIRT1 and Nrf2 in nucleus pulposus cells （P<0.05）. Compared with the high-dose Shentong Zhuyutang-containing serum+IL-1β group， the ML385 group showed down-regulated protein levels of Nrf2 and GPX4， lowered GSH level， and elevated Fe²⁺ and MDA levels （P<0.05）. In addition， the Ex 527 group showed down-regulated protein levels of SIRT1， Nrf2， and GPX4 （P<0.05）. The results of the animal experiment showed that compared with the sham operation group， the model group had severe degeneration of the intervertebral disc tissue with increased pathological score， up-regulated protein level of ACSL4 （P<0.05）， and down-regulated protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ （P<0.05）. Compared with the model group， the Shentong Zhuyutang group showed alleviated IDD with declined pathological score， down-regulated protein level of ACSL4 （P<0.05）， and up-regulated protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ （P<0.05）. ConclusionShentong Zhuyutang may activate the SIRT1/Nrf2 signaling pathway to inhibit the ferroptosis of nucleus pulposus cells， thereby delaying the process of IDD in rats.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.