The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Age-related macular degeneration(ARMD)is the leading cause of blindness in the elderly. Studies have shown that the regulation disorder of extracellular matrix(ECM)is one of the important characteristics of ARMD, and its damage can be sustained throughout the disease course. Additionally, various cell types participate in the formation and abnormal deposition of ECM under the control of multiple signals. Subsequently, they transmit signals that regulate adhesion, migration, proliferation, apoptosis, survival or differentiation, which lead to the destruction of the retinal and choroidal microenvironment, immune dysfunction, infiltrative inflammatory cell differentiation, neovascularization and epithelial mesenchymal transformation, and ultimately lead to subretinal fibrosis, scarring and severe visual impairment in advanced ARMD. Therefore, increasing attention has been paid to the role of ECM in ARMD in recent years. This article reviews the relationship between retinal ECM and ARMD and the role between ECM and various types of cells in ARMD, hoping to provide guidance for the research direction of ARMD treatment.

OBJECTIVE To evaluate the clinical efficacy of modified Zhujing Pills in the treatment of dry age-related macular degeneration(AMD)of liver and kidney insufficiency type.METHODS 64 patients with dry AMD of liver and kidney insufficiency type were randomly divided into an experimental group and a control group,32 patients each.The control group was given oral treat-ment with Laishiding capsules,and the experimental group was given oral treatment with modified Zhujing Pills granules.The treatment course for both groups was 3 months.Before and after treatment,the patients in the two groups were observed for TCM syndrome scores,visual acuity,fundus autofluorescence(AF),changes in drusen area within 5 mm of the fovea,and plasma superoxide dis-mutase(SOD),glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)levels.RESULTS After treatment,the scores of TCM syndromes in the experimental group were significantly reduced(P＜0.05,P＜0.01),and the efficacy of TCM syn-dromes was better than that of the control group(P＜0.01);the visual acuity of the patients in the experimental group was significantly improved,AF was significantly weakened and the area of drusen was reduced(P＜0.05,P＜0.01),which were better than those in the control group(P＜0.05);the plasma SOD and GSH-Px activities of the experimental group were increased,and the MDA level was significantly lowered(P＜0.05,P＜0.01),which were better than the control group(P＜0.05).CONCLUSION Modified Zhujing Pills can reduce fundus AF intensity,decrease macular drusen area,improve visual acuity,and reduce TCM syndrome scores in pa-tients with dry AMD.The therapeutic mechanism may be related to its antioxidant effect.

Objective To explore whether liver cirrhosis markers aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4 index(FIB-4)based on blood biochemical indicators can predict disease free survival(DFS)and overall survival(OS)in patients with hepatocellular carcinoma(HCC)after resection.Methods 300 patients with HCC who underwent radical resection in Zhongshan Hospital,Fudan University from February 2005 to July 2017 were enrolled and the clinicopathological characteristics,recurrence and survival of these patients were retrospectively collected.The relationships between APRI,FIB-4 and postoperative recurrence and survival were evaluated.The ROC curve was used to evaluate the predictive values of APRI,FIB-4.Results The median follow-up of 300 patients was 61 months.Univariate Cox regression analysis showed that APRI,FIB-4,vascular invasion were risk factors affecting postoperative DFS and OS.The multivariate Cox regression analysis showed that vascular invasion was the independent risk factor for postoperative DFS(HR=1.518,95%CI 1.024-2.252,P=0.038)and OS(HR=2.301,95%CI 1.270-4.167,P=0.006).The time dependent ROC(time-ROC)curve showed that AUCs of APRI and FIB-4 predicting 1-year,3-year,and 5-year DFS were 0.555-0.596,which were 0.600-0.679 when predicting 1-year,3-year,and 5-year OS.Conclusions The predictive value of APRI and FIB-4 based on blood biochemical indicators alone for postoperative DFS and OS in HCC patients is limited.

Objective To investigate the intervention effects of Yangqing Chenfei Fang (YCF), Baojin Chenfei Fang (BCF), and Jinshui Chenfei Fang (JCF) at different pathological stages of silicosis in a rat model. Methods A total of 216 specific pathogen free rats were randomly divided into control group, silicosis group, tetrandrine group, YCF group, BCF group and JCF group, with 35-36 rats in each group (11-12 rats at each time point). The rats in control group were treated with intragastric administration of pure water [administration volume at 2.5 mL/(kg·time)], while the rats of other five groups were treated with silica suspension at 250 mg/kg body weight to induce a silicosis model using the one-time non-exposed tracheal method. Intragastric administration of the corresponding drugs was performed at three time points at days 1-14 (early stage of silicosis), days 15-28 (middle stage of silicosis), and days 29-42 (late stage of silicosis) after modeling. Pulmonary function enhanced pause (Penh), forced vital capacity (FVC), and dynamic lung compliance (Cdyn) of rats in the six groups was assessed on days 15, 29, and 43 after modeling. Histopathological changes in lung tissues were observed, and relative expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, hydroxyproline, collagenⅠ(COL-Ⅰ), and α-smooth muscle actin (α-SMA) were detected in lung tissues. Results i) Pulmonary function index. The index of Penh in three stages of silicosis of rats in YCF group, BCF group and JCF group was lower than that in the silicosis group at the same stage (all P<0.05), and the index of Penh was higher than that in the tetrandrine group at the same stage (all P<0.05). The index of FVC of rats in YCF group, BCF group and JCF group at the middle stage was higher than that in the silicosis group at the same stage (all P<0.05), as well as the index of Cdyn was higher than that in the tetrandrine group at the same stage (all P<0.05). ii) Histopathology of lung tissue. Rats of the silicosis group exhibited alveolitis, fibro stripe, and collagen deposition in lung tissues in the early stage compared with rat of the control group, with fibrosis progressively worsening over time and inflammation persisting throughout the disease course. Pathological changes of lung tissues were alleviated to varying degrees in the tetrandrine groups, YCF group, BCF group and JCF group compared with that of the silicosis group. Compared with the same stage of silicosis group, the Ashcroft scores of lung tissues in the YCF group and BCF group were lower in the middle and late stages (all P<0.05). The Ashcroft score of lung tissues in the BCF group in the middle and late stages was lower than that in tetrandrine group at the same stage (all P<0.05), while the Ashcroft score in the middle stages was lower than that in YCF group at the same stage (P<0.05). The Ashcroft score of lung tissue in the JCF group was lower than that in the silicosis group, tetrandrine group and YCF group at all three stages (all P<0.05), and was lower than that in BCF group at the early and late stage of silicosis (all P<0.05). iii) Inflammatory factors. IL-6 level in the lung tissues in the YCF group, BCF group and JCF group decreased compared with that in the silicosis group at the same stage (all P<0.05), while IL-1β and TNF-α levels decreased at the early and middle stages (all P<0.05), hydroxyproline level decreased at all three stages (all P<0.05). iv) Collagen. The relatively expression of COL-Ⅰ in the lung tissues in the YCF group decreased at the late stage of silicosis compared with that in the silicosis group at the same stage (all P<0.05), while the relatively expression of α-SMA decreased at the middle and late stages (all P<0.05). Compared with the same stage of silicosis group, the relative expression of COL-Ⅰ and α-SMA of the lung tissues reduced in the BCF group and JCF group at all stages (all P<0.05). The relative expression of COL-Ⅰ of the lung tissues reduced in the BCF group at the late stage compared with that in the YCF group in the same stage (all P<0.05), while the relative expression of α-SMA decreased at the early and middle stages (all P<0.05). The relative expression of COL-Ⅰ of the lung tissues reduced in the JCF group at late stage of silicosis (all P<0.05), while the relative expression of α-SMA decreased at all three stages (all P<0.05), compared with the same stage of YCF group. Conclusion All three formulations of Chinese herbs are effective in improving lung function and alleviating the progress of lung inflammation and fibrosis. YCF is the most effective in suppressing inflammation in the early stage of silicosis. BCF excels in delaying fibrosis in the early and middle stages. JCF is the most effective in improving lung function and delaying fibrosis progression in the late stage.

Background/Aims: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. Methods: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. Results: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). Conclusions IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8⁺ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8⁺ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8⁺ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.