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.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: To assess the effect of transarterial embolization (TAE) for adhesive capsulitis (AC) by evaluating clinical outcomes and changes in inflammation using magnetic resonance imaging (MRI). Materials and Methods: Patients who had undergone TAE between August 2020 and August 2023 for AC refractory to conservative treatments without any invasive procedures for more than 3 months, and had undergone baseline and 3-month post-AC follow-up contrast-enhanced MRI evaluations, were included. A suspension mixture of 500 mg imipenem/cilastatin in 10 mL of iodinated contrast agent was used for TAE. MRI results were analyzed to assess periarticular capsule/ligament inflammation. Clinical assessments included pain scores using the numeric rating scale (NRS) and functional scores using the quick disabilities of the arm, shoulder, and hand (Quick DASH) questionnaire. Results: Twenty-five patients (female:male, 14:11; age, 54.9 ± 7.1 years) were included. Significant reductions in average NRS pain scores as well as improvements in Quick DASH scores and range of motion, including anterior flexion and abduction, were observed at 1, 3, and 6 months after TAE (all P < 0.001). MRI analyses revealed that TAE significantly decreased the grades of axillary recess capsule enhancement, rotator interval (RI) capsule T2 signal intensity, and RI capsule enhancement (all P ≤ 0.004). Conclusion TAE may be an effective and safe therapeutic approach for AC refractory to conservative treatments, alleviating pain and supporting functional recovery. The observed MRI findings suggest that the effectiveness of TAE for AC may be attributed to the reduction of inflammation and the elimination of angiogenesis.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

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.

The Maillard reaction is a complex process in which amine compounds such as amino acids， peptides， and proteins undergo condensation， polymerization， and other reactions with carbonyl compounds such as reducing sugars， ketones， and aldehydes at room temperature or under heating conditions， ultimately producing substances such as melanoidins and aromatic compounds. The processing of traditional Chinese medicine（TCM） often involves heating and the addition of auxiliary materials， providing complete conditions for the occurrence of the Maillard reaction. The Maillard reaction is affected by various factors such as temperature， pH， moisture， substrate， reaction time and pressure， the progress of the reaction also affected by different processing technologies of TCM and the addition of different excipients. The Maillard reaction involves multiple substances， most of which have significant physiological activity or toxicity， affecting the efficacy and pharmacological effects of TCM. It can also produce various flavor substances and browning products that change the flavor and color of TCM. The Maillard reaction mechanism， influencing factors， related components， and the impact of Maillard reaction on various aspects of TCM processing are reviewed from multiple perspectives in this article， providing reference for the further improvement of processing mechanism and quality control of TCM.

Objective To evaluate the survival outcomes of segmentectomy versus lobectomy for T1c non-small cell lung cancer (NSCLC). Methods We searched PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI (China National Knowledge Infrastructure), and Wanfang Data, with the search time limit set from the inception of the databases to February 2024. Three researchers independently screened the literature, extracted relevant information, and evaluated the risk of bias of the included literature according to the Newcastle-Ottawa Scale (NOS). Meta-analysis was conducted using STATA 15.1. Results A total of 8 retrospective cohort studies were included, involving 7 433 patients. The NOS scores of the included studies were all ≥7 points. Patients who underwent lobectomy had significantly higher five-year overall survival (OS) rates compared to those who underwent segmentectomy (adjusted HR=1.11, 95%CI 0.99-1.24, P=0.042). Compared with lobectomy, segmentectomy showed no significant difference in adjusted three-year OS rate (adjusted HR=0.88, 95%CI 0.62-1.24) and adjusted five-year lung cancer-specific survival (adjusted HR=1.10, 95%CI 0.80-1.51, P=0.556) of patients with T1c NSCLC. Moreover, there were no differences in the five-year adjusted relapse-free survival (adjusted HR=1.23, 95%CI 0.82-1.85, P=0.319), and adverse events (OR=0.57, 95%CI 0.37-0.90, P=0.015) in the segmentectomy group were significantly less than those in the lobectomy group. Subgroup analysis based on whether patients received neoadjuvant therapy showed that among studies that excluded patients who received neoadjuvant therapy, no significant difference in 5-year adjusted OS rate was observed between the segmentectomy group and lobectomy group (adjusted HR=1.02, 95%CI 0.81-1.28, P=0.870). Conclusion Segmentectomy and lobectomy show no significant difference in long-term survival in stage T1c NSCLC patients, with segmentectomy associated with fewer postoperative complications. Further high-quality research is needed to confirm the comparative efficacy and safety of lobectomy and segmentectomy for T1c NSCLC patients.

Isoliquiritigenin (ISL) is a chalcone compound isolated from licorice, known for its anti-diabetic, anti-cancer, and antioxidant properties. Our previous study has demonstrated that ISL effectively lowers blood glucose levels in type 2 diabetes mellitus (T2DM) mice and improves disturbances in glucolipid and energy metabolism induced by T2DM. This study aims to further investigate the effects of ISL on alleviating abnormal endoplasmic reticulum stress (ERS) caused by T2DM and to elucidate its molecular mechanisms. In vivo experiments were conducted using 8-week-old SPF male C57BL/6J mice. The T2DM animal model was established by high-fat and high-sugar diet combined with intraperitoneal injections of streptozotocin (STZ), in compliance with the ethical guidelines set by the Animal Welfare Committee of Beijing University of Chinese Medicine (approval number: BUCM-2022021503-1134). In vitro experiments employed human liver cancer HepG2 cells, which were induced with tunicamycin (TM) to establish the ERS cell model. Transcriptomic sequencing was used to analyze changes in gene expression in the liver samples of T2DM mice following ISL treatment. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to assess the regulatory effects of ISL on key ERS genes. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunofluorescence techniques were used to evaluate ISL's effects on ERS-related proteins. Results indicate that ISL significantly downregulates the expression of ERS-related genes, reduces the level of glucose-regulated protein 78 (GRP78), and inhibits the phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), thereby alleviating abnormal ERS induced by T2DM. Additionally, ISL increases the protein levels of insulin receptor substrate (IRS) 1 and IRS2 and enhances the phosphorylation of protein kinase B (Akt), thereby improving insulin sensitivity. In conclusion, ISL is able to alleviate T2DM associated symptoms by improving abnormal ERS and enhancing insulin sensitivity.

Objective To analyze the trends in the disease burden of schistosomiasis in China from 1992 to 2021, and to project the disease burden of schistosomiasis in China from 2022 to 2030, so as to provide insights into the elimination of schistosomiasis in China. Methods The prevalence, age-standardized prevalence, disability-adjusted life year (DALYs) rate and age-standardized DALYs rate of schistosomiasis, as well as the years lost due to disability (YLDs) rate and age-standardized YLDs rate of anemia attributable to Schistosoma infections in China, the world and different socio-demographic index (SDI) regions were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources, and the trends in the disease burden due to schistosomiasis were evaluated with estimated annual percentage change (EAPC) and its 95% confidence interval (CI). In addition, the age, period and cohort effects on the prevalence of schistosomiasis were examined in China using an age-period-cohort (APC) model, and the disease burden of schistosomiasis was predicted in China from 2022 to 2030 using a Bayesian age-period-cohort (BAPC) model. Results The age-standardized prevalence and DALYs rate of schistosomiasis, and the age-standardized YLDs rate of anemia attributable to Schistosoma infections were 761.32/10⁵, 5.55/10⁵ and 0.38/10⁵ in China in 2021. These rates were all lower than the global levels (1 914.30/10⁵, 21.90/10⁵ and 3.36/10⁵, respectively), as well as those in the medium SDI regions (1 413.61/10⁵, 12.10/10⁵ and 1.93/10⁵, respectively), low-medium SDI regions (2 461.03/10⁵, 26.81/10⁵ and 4.48/10⁵, respectively), and low SDI regions (5 832.77/10⁵, 94.48/10⁵ and 10.65/10⁵, respectively), but higher than those in the high SDI regions (59.47/10⁵, 0.49/10⁵ and 0.05/10⁵, respectively) and high-medium SDI regions (123.11/10⁵, 1.20/10⁵ and 0.12/10⁵, respectively). The prevalence and DALYs rate of schistosomiasis were higher among men (820.79/10⁵ and 5.86/10⁵, respectively) than among women (697.96/10⁵ and 5.23/10⁵, respectively) in China in 2021, while the YLDs rate of anemia attributable to Schistosoma infections was higher among women (0.66/10⁵) than among men (0.12/10⁵). The prevalence of schistosomiasis peaked at ages of 30 to 34 years among both men and women, while the DALYs rate of schistosomiasis peaked among men at ages of 15 to 19 years and among women at ages of 20 to 24 years. The age-standardized prevalence of schistosomiasis showed a moderate decline in China from 1992 to 2021 relative to different SDI regions [EAPC = -1.51%, 95% CI: (-1.65%, -1.38%)], while the age-standardized DALYs rate [EAPC = -3.61%, 95% CI: (-3.90%, -3.33%)] and age-standardized YLDs rate of anemia attributable to Schistosoma infections [EAPC = -4.16%, 95% CI: (-4.38%, -3.94%)] appeared the fastest decline in China from1992 to 2021 relative to different SDI regions. APC modeling showed age, period, and cohort effects on the trends in the prevalence of schistosomiasis in China from 1992 to 2021, and the prevalence of schistosomiasis appeared a rise followed by decline with age, and reduced with period and cohort. BAPC modeling revealed that the age-standardized prevalence and age-standardized DALYs rate of schistosomiasis, and age-standardized YLDs rate of anemia attributable to Schistosoma infections all appeared a tendency towards a decline in China from 2022 to 2030, which reduced to 722.72/10⁵ [95% CI: (538.74/10⁵, 906.68/10⁵)], 5.19/10⁵ [95% CI: (3.54/10⁵, 6.84/10⁵)] and 0.30/10⁵ [95% CI: (0.21/10⁵, 0.39/10⁵)] in 2030, respectively. Conclusions The disease burden of schistosomiasis appeared a tendency towards a decline in China from 1992 to 2021, and is projected to appear a tendency towards a decline from 2022 to 2030. There are age, period and cohort effects on the prevalence of schistosomiasis in China. Precision schistosomiasis control is required with adaptations to current prevalence and elimination needs.

Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.