Objective To describe the significance of the pretreatment inflammatory indicators in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after undergoing radical radiotherapy. Methods The data of 246 ESCC patients who underwent radical radiotherapy were retrospectively collected. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values for platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). The Kaplan-Meier method was used for survival analysis. We conducted univariate and multivariate analyses by using the Cox proportional risk regression model. Software R (version 4.2.0) was used to create the nomogram of prognostic factors. Results The results of the ROC curve analysis showed that the optimal cutoff values of PLR, NLR, and SII were 146.06, 2.67, and 493.97, respectively. The overall response rates were 77.6% and 64.5% in the low and high NLR groups, respectively (P<0.05). The results of the Kaplan-Meier survival analysis revealed that the prognosis of patients in the low PLR, NLR, and SII group was better than that of patients in the high PLR, NLR, and SII group (all P<0.05). The results of the multivariate Cox regression analysis showed that gender, treatment modalities, T stage, and NLR were independent factors affecting the overall survival (OS). In addition, T stage and NLR were independent factors affecting the progression-free survival (PFS) (all P<0.05). The nomogram models of OS and PFS prediction were established based on multivariate analysis. The C-index values were 0.703 and 0.668. The calibration curves showed excellent consistency between the predicted and observed OS and PFS. Conclusion The pretreatment values of PLR, NLR, and SII are correlated with the prognosis of patients with ESCC who underwent radical radiotherapy. Moreover, NLR is an independent factor affecting the OS and PFS of ESCC patients. The NLR-based nomogram model has a good predictive ability.

With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

Since its establishment in 2016, the National Rare Diseases Registry System of China (NRDRS) has accumulated valuable case data and bio-specimen for basic and clinical research on rare diseases in China. However, the emerging challenges in clinical diagnosis and treatment of rare diseases make it unable for data and resource platform to fully meet the diversified needs. Under this backdrop, we have developed a protocol to optimize and upgrade the system based on the core functions of the NRDRS platform. The goal is to leverage intelligent digital technologies to transform NRDRS into a new platform integrating multimodal data and auxiliary diagnostic and treatment functions. It is specified as the development and construction of "one platform and four intelligent tools." Currently, we have upgraded and developed NRDRS platform, intelligent tool for genotype-phenotype analysis of rare diseases, AI-assisted diagnostic tool for rare diseases, remote multidisciplinary diagnosis and teaching tool for rare diseases, drug screening and validation tool for rare diseases. The next step will focus on the promotion of the application of these tools in clinical settings in order to address the issue of severe imbalance in the allocation of resources for the diagnosis and treatment of rare diseases. This article provides an overview of the digital and intelligent upgrades of the NRDRS, the trials in applications in clinical settings, and direction in the future.

ObjectiveAccording to the theory of medicinal properties in traditional Chinese medicine （TCM）， Tangye Jingfa Tu， implying that all tonic prescriptions should primarily feature sweetness. However， the "Chart of the Classic Methods of Decoction Therapy" recorded in Mnemonic Aids for Medical Practice （Fuxingjue） proposes that each of the Zangfu organs has a corresponding tonifying flavor， i.e.， pungent for the liver， salty for the heart， sweet for the spleen， sour for the lungs， and bitter for the kidneys. Therefore， deficiency syndromes of different organs should be primarily addressed with specific medicinal flavors. This study applies this theoretical framework to analyze the formulation and compatibility principles and efficacy positioning of commonly used TCM tonic prescriptions， providing a reference for differentiated clinical medication. MethodsA database of tonic prescriptions was established based on the textbook Science of Prescriptions. Excel software was used to separately calculate the number of medicinal types， frequency of use， flavors， and proportional composition of the prescriptions. The prescriptions were categorized to determine their compatibility structures and functional characteristics. ResultsA total of 60 prescriptions were included， classified into six categories， involving 110 medicinal types with 469 instances of use. From the perspective of the "Chart of the Classic Methods of Decoction Therapy"， different tonic prescriptions exhibit distinct dominant medicinal flavors and organ associations. Specifically， 15 Qi-tonifying prescriptions primarily adopted a "sweet flavor" to tonify the spleen. Nine blood-tonifying prescriptions primarily adopted a "pungent-salty flavor" to tonify the liver and heart. Seven Qi-and-blood-tonifying prescriptions primarily featured a "sweet-pungent flavor" to tonify the spleen and liver. Nineteen Yin-tonifying prescriptions primarily adopted a "bitter-sour flavor" to tonify the kidneys and lungs. Seven Yang-tonifying prescriptions primarily featured a "pungent-bitter flavor" to tonify the liver and kidneys. Three Yin-and-Yang-tonifying prescriptions primarily featured a "bitter-pungent-sweet flavor" to tonify the kidneys， liver， and spleen. ConclusionThe "Chart of the Classic Methods of Decoction Therapy" clearly illustrates the formulation and compatibility principles and key differences among various tonic prescriptions， indicating that not all tonic prescriptions are predominantly sweet in flavor. This provides new insights for the clinical modification and application of tonic prescriptions.

ObjectiveAccording to the theory of medicinal properties in traditional Chinese medicine （TCM）， Tangye Jingfa Tu， implying that all tonic prescriptions should primarily feature sweetness. However， the "Chart of the Classic Methods of Decoction Therapy" recorded in Mnemonic Aids for Medical Practice （Fuxingjue） proposes that each of the Zangfu organs has a corresponding tonifying flavor， i.e.， pungent for the liver， salty for the heart， sweet for the spleen， sour for the lungs， and bitter for the kidneys. Therefore， deficiency syndromes of different organs should be primarily addressed with specific medicinal flavors. This study applies this theoretical framework to analyze the formulation and compatibility principles and efficacy positioning of commonly used TCM tonic prescriptions， providing a reference for differentiated clinical medication. MethodsA database of tonic prescriptions was established based on the textbook Science of Prescriptions. Excel software was used to separately calculate the number of medicinal types， frequency of use， flavors， and proportional composition of the prescriptions. The prescriptions were categorized to determine their compatibility structures and functional characteristics. ResultsA total of 60 prescriptions were included， classified into six categories， involving 110 medicinal types with 469 instances of use. From the perspective of the "Chart of the Classic Methods of Decoction Therapy"， different tonic prescriptions exhibit distinct dominant medicinal flavors and organ associations. Specifically， 15 Qi-tonifying prescriptions primarily adopted a "sweet flavor" to tonify the spleen. Nine blood-tonifying prescriptions primarily adopted a "pungent-salty flavor" to tonify the liver and heart. Seven Qi-and-blood-tonifying prescriptions primarily featured a "sweet-pungent flavor" to tonify the spleen and liver. Nineteen Yin-tonifying prescriptions primarily adopted a "bitter-sour flavor" to tonify the kidneys and lungs. Seven Yang-tonifying prescriptions primarily featured a "pungent-bitter flavor" to tonify the liver and kidneys. Three Yin-and-Yang-tonifying prescriptions primarily featured a "bitter-pungent-sweet flavor" to tonify the kidneys， liver， and spleen. ConclusionThe "Chart of the Classic Methods of Decoction Therapy" clearly illustrates the formulation and compatibility principles and key differences among various tonic prescriptions， indicating that not all tonic prescriptions are predominantly sweet in flavor. This provides new insights for the clinical modification and application of tonic prescriptions.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Objective: To investigate the clinical efficacy of en bloc resection of ureteral orifice in the treatment of tumors around ureteral orifice. Methods: Clinical data of 43 patients treated at our hospital during Jul.2018 and Jun.2023 were retrospectively analyzed，including 34 male and 9 female patients.Prior to surgical intervention，all patients were diagnosed with bladder masses via imaging or cystoscopy，and no concurrent upper urinary tract tumors were detected.The initial surgical procedure was transurethral resection of bladder tumor，which removed the tumors around ureteral orifice.Subsequently，electrocoagulation was employed for hemostasis，followed by the placement of a double-J tube into the affected ureter.Tumor recurrence and hydronephrosis were observed after operation. Results: All operations were successful without conversion to open surgery.The operation time was (61±25) min.The postoperative pathological results showed 28 cases of Ta stage tumors，14 cases of T1 stage tumors，and 1 case of T2 stage tumor.During the follow-up of (17±11) months，8 patients (19%) had tumor recurrence，among whom 4 (9%) had recurrent tumor involving the ureteral orifice，and 1 (2%) had transient hydronephrosis after removal of double-J tube. Conclusion: The en bloc resection of the ureteral orifice with placement of a double-J tube is safe and effective for the treatment of tumors around the ureteral orifice，with low recurrence rate.It is an optional procedure for early stage patients.

Objective: To investigate the clinical efficacy of transurethral 450 nm blue laser vaporization of prostate (BVP) and transurethral plasmakinetic resection of the prostate (PKRP) in the treatment of frail elderly patients with benign prostatic hyperplasia (BPH). Methods: A retrospective analysis was conducted on the clinical data of 62 frail elderly BPH patients undergoing BVP (n=32) or PKRP (n=30) in our hospital during Jan.2023 and Jun.2024.The two groups were compared in terms of postoperative hemoglobin drop, operation time, hospital stay, catheter indwelling time, bladder irrigation time, preoperative and postoperative 3-month postvoid residual (PVR), maximum urinary flow rate (Qmax), international prostate symptom score (IPSS), quality of life score (QoL), and postoperative complications. Results: The postoperative hemoglobin drop was lower in the BVP group than in the PKRP group [(1.62±1.04) g/L vs.(7.37±2.37) g/L, P＜0.001].The operation time [(24.53±7.52) min vs. (47.77±11.12) min], hospital stay [(2.78±1.62) d vs. (8.13±0.82) d], catheter indwelling time [(1.84±0.99) d vs. (5.40±0.81) d], and bladder irrigation time [(7.37±2.35) h vs. (51.60±19.72) h] were significantly shorter in the BVP group than in the PKRP group (all P＜0.001).At 3 months postoperatively, both groups showed significant improvements in IPSS, QoL, Qmax, and PVR compared to preoperative levels (P＜0.05), but there were no significant differences between the two groups (P>0.05).The overall incidence of early postoperative complications in the BVP group was lower than that in PKRP group (18.75% vs. 43.33%, P＜0.05).After 3 months of follow-up, there was no significant difference in the incidence of complications between the BVP group and PKRP group(3.13% vs. 13.33%, P=0.14). Conclusion: BVP for the treatment of frail elderly BPH patients is safe and reliable, associated with minimal bleeding, short operation time, catheterization time and hospital stay, and there is no need to discontinue anticoagulant drugs.