Alcoholic liver disease(ALD), a major cause of chronic liver disease worldwide, poses a serious threat to human health. Despite the availability of various drugs for treating ALD, their efficacy is often uncertain, necessitating the search for new therapeutic approaches. Traditional Chinese medicine polysaccharides have garnered increasing attention in recent years due to their versatility, high efficiency, and low side effects, and they have demonstrated significant potential in preventing and treating ALD. Emerging studies have suggested that these polysaccharides exert their therapeutic effects through multiple mechanisms, including the inhibition of oxidative stress and the regulation of lipid metabolism, gut microbiota, and programmed cell death. This review summarizes the recent research progress in the pharmacological effects and regulatory mechanisms of traditional Chinese medicine polysaccharides in treating ALD, aiming to provide a scientific basis and theoretical support for their application in the prevention and treatment of ALD.
Humans ; Liver Diseases, Alcoholic/metabolism* ; Polysaccharides/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Oxidative Stress/drug effects* ; Medicine, Chinese Traditional ; Gastrointestinal Microbiome/drug effects* ; Lipid Metabolism/drug effects*

The present study delves into the cellular mechanisms underlying the antiviral effects of dehydrodiisoeugenol(DEH) by focusing on the transcription factor EB(TFEB)/autophagy-lysosome pathway. The cell counting kit-8(CCK-8) was utilized to assess the impact of DEH on the viability of human non-small cell lung cancer cells(A549). The inhibitory effect of DEH on the replication of influenza A virus(H1N1) was determined by real-time quantitative polymerase chain reaction(RT-qPCR). Western blot was employed to evaluate the influence of DEH on the expression level of the H1N1 virus nucleoprotein(NP). The effect of DEH on the fluorescence intensity of NP was examined by the immunofluorescence assay. A mouse model of H1N1 virus infection was established via nasal inhalation to evaluate the therapeutic efficacy of 30 mg·kg~(-1) DEH on H1N1 virus infection. RNA sequencing(RNA-seq) was performed for the transcriptional profiling of mouse embryonic fibroblasts(MEFs) in response to DEH. The fluorescent protein-tagged microtubule-associated protein 1 light chain 3(LC3) was used to assess the autophagy induced by DEH. Western blot was employed to determine the effect of DEH on the autophagy flux of LC3Ⅱ/LC3Ⅰ under viral infection conditions. Lastly, the role of TFEB expression in the inhibition of DEH against H1N1 infection was evaluated in immortalized bone marrow-derived macrophage(iBMDM), both wild-type and TFEB knockout. The results revealed that the half-maximal inhibitory concentration(IC_(50)) of DEH for A549 cells was(87.17±0.247)μmol·L~(-1), and DEH inhibited H1N1 virus replication in a dose-dependent manner in vitro. Compared with the H1N1 virus-infected mouse model, the treatment with DEH significantly improved the body weights and survival time of mice. DEH induced LC3 aggregation, and the absence of TFEB expression in iBMDM markedly limited the ability of DEH to counteract H1N1 virus replication. In conclusion, DEH exerts its inhibitory activity against H1N1 infection by activating the TFEB/autophagy-lysosome pathway.
Influenza A Virus, H1N1 Subtype/genetics* ; Animals ; Autophagy/drug effects* ; Humans ; Mice ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Influenza, Human/metabolism* ; Lysosomes/metabolism* ; Orthomyxoviridae Infections/genetics* ; Eugenol/pharmacology* ; Antiviral Agents/pharmacology* ; Virus Replication/drug effects* ; A549 Cells ; Male

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Objective To establish an artificial intelligence(AI)diagnostic model for the histopathologic diagnosis of extramammary Paget's disease(EMPD)and to evaluate its efficiency for the diagnosis and differential diagnosis of EMPD.Methods All non-tumor skin disease patients who underwent skin tissue biopsy in Department of Dermatology of First Affiliated Hospital of Army Medical University from September 2003 to February 2023 were recruited,and their pathological data were collected,including EMPD,Bowen's disease(BD),squamous cell carcinoma(SCC),and epidermal hyperplasia and hypertrophy.With EMPD as the main research subject,the histopathological images of BD,SCC,and non-tumor skin diseases were included in the study.The histopathological data of 4 types of diseases was classified and diagnosed by ResNet101 and DenseNet121 deep learning neural networks,and the performance of these models was evaluated.Results The AUC values of the ResNet101 diagnostic model for the diagnosis of EMPD,BD,SCC and non-tumor skin diseases on the images at x20 magnification were 0.97,0.98,1.00 and 0.96,respectively,with an accuracy of 0.925±0.011,while the AUC values on the images at x40 magnification were 1.00,0.99,1.00 and 0.97,respectively,with an accuracy of 0.943±0.017.The AUC values of the DenseNet121 diagnostic model for the diagnosis of 4 diseases on the images at x20 magnification were 0.98,0.95,0.99 and 1.00,respectively,with an accuracy of 0.912±0.034,while the AUC values on the images at x40 magnification were 0.99,0.96,1.00 and 1.00,respectively,with an accuracy of 0.971±0.012.Our results indicated that the histopathologic diagnostic model could effectively differentiate EMPD from BD,SCC and non-tumor skin diseases at low power magnification.The FLPOs of ResNet101 was 786.6 M,and the parameter was 4.5 M;The FLPOs of DensNet121 was 289.7 M,and the parameter was 0.8M.Conclusion Our AI diagnostic model is of good effectiveness in the diagnosis and differential diagnosis of EMPD.DenseNet121 is recommended as the dermatopathological diagnostic model of this study.

Chronic kidney disease(CKD)commonly used dietary assessments including 24-hour dietary recall(24 h DR)/3-day dietary recall(3DDR),food frequency questionnaire(FFQ),dietary records,and estimation of dietary protein intake based on nitrogen balance.Given the high prevalence of CKD patients in Asian population and the scarcity of research using FFQ method,it is crucial to develop an FFQ suitable for Chinese CKD patients.This review summarizes the advantages and disadvantages of dietary assessment methods for CKD,the current research status,and the content and steps involved in establishing an FFQ,with the aim of providing reference for the modification of FFQ for Chinese CKD patients.

AIM To investigate the effects of Zuogui Jiangtang Tongmai Recipe on necroptosis pathway in a rat model of type 2 diabetes mellitus(T2DM)complicated with cerebral infarction(CI).METHODS The SD rats were randomly divided into the sham operation group,the model group,the metformin group(0.045 g/kg),and the low,medium and high dose Zuogui Jiangtang Tongmai Recipe groups(6.5,13,26 g/kg),with 9 rats in each group.In contrast to rats of the sham operation group,rats of the other groups were given 4 weeks feeding of high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish a T2DM rat model with one week stable blood glucose,followed by gavage of corresponding drugs 3 days before the establishment of the middle cerebral artery occlusion(MCAO)model.After 7 days of administration,the rats had their CI injury assessed by mNSS method and TTC staining;their level of blood glucose detected by blood glucose meter;their levels of glycated serum protein,serum TNF-α and IL-1β detected by ELISA;their cerebral mRNA expressions of FADD,RIPK1,RIPK3 and MLKL detected by RT-qPCR;and their cerebral protein expressions of FADD,p-RIPK1,p-RIPK3 and p-MLKL detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased levels of blood glucose value,glycosylated serum protein,neurological function score,cerebral infarction volume,cerebral FADD,RIPK1,RIPK3 and MLKL mRNA expressions,cerebral FADD,p-RIPK1,p-RIPK3 and p-MLKL protein expressions,serum TNF-α and IL-1β levels(P＜0.01);and more disordered and morphologically diverse neurons with smaller nucleus.Compared with the model group,the groups intervened with medium or high dose Zuogui Jiangtang Tongmai Recipe,or metformin shared improvement in terms of the aforementioned indices(P＜0.05,P＜0.01);and more neurons with regular morphology neat arrangement,and reduced cell gap.CONCLUSION Zuogui Jiangtang Tongmai Recipe can improve the neurological dysfunction of the rat model of T2DM complicated with CI,which may associate with the inhibited activation of necroptosis signaling pathway.

Accurate receptor/ligand binding free energy calculations can greatly accelerate drug discovery by identifying highly potent ligands. By simulating the change from one compound structure to another, the relative binding free energy (RBFE) change can be calculated based on the theoretically rigorous free energy perturbation (FEP) method. However, existing FEP-RBFE approaches may face convergence challenges due to difficulties in simulating non-physical intermediate states, which can lead to increased computational costs to obtain the converged results. To fundamentally overcome these issues and accelerate drug discovery, a new combined-structure RBFE (CS-FEP) calculation strategy was proposed, which solved the existing issues by constructing a new alchemical pathway, smoothed the alchemical transformation, increased the phase-space overlap between adjacent states, and thus significantly increased the convergence and accelerated the relative binding free energy calculations. This method was extensively tested in a practical drug discovery effort by targeting phosphodiesterase-1 (PDE1). Starting from a PDE1 inhibitor (compound 9, IC₅₀ = 16.8 μmol/L), the CS-FEP guided hit-to-lead optimizations resulted in a promising lead (11b and its mesylate salt formulation 11b-Mesylate, IC₅₀ = 7.0 nmol/L), with ∼2400-fold improved inhibitory activity. Further experimental studies revealed that the lead showed reasonable metabolic stability and significant anti-fibrotic effects in vivo.

Malnutrition is a significant risk factor for the progression of chronic kidney disease(CKD),and monitoring the nutritional status of CKD patients is crucial for delaying disease progression and improving patient prognosis.Currently,there is a scarcity of studies on malnutrition in CKD,and a unified standard for nutritional assessment in CKD is still lacking.Clinical evaluation must be conducted according to the condition of patients,combined with multiple indicators.Nutritional screening and assessment scales are the common nutritional assessment methods;however,due to limitations in the applicable populations,the applicability of some scales for the CKD population requires further verification.Additionally,anthropometric indicators,body composition analysis,and clinical laboratory indicators can also reflect human nutritional status,each with its respective advantages and limitations.This review summarizes the research status and clinical application characteristics of various nutritional assessment methods in CKD patients,aiming to provide references for the clinical assessment of malnutrition in CKD.

In this study, the ovarian surgery (ovariectomy, OVX) was used to establish the osteoporosis mice model of primary menstruation, in order to evaluate the protective effects and mechanisms of Zhibai Dihuang decotion on postmenopausal osteoporosis (PMOP). The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University (number: 20210315-03), in compliance with the Institutional Animal Care Guidelines. C57BL/6 mice were divided into five groups, including Sham group, OVX group, low (32 g·kg^-1·day^-1) and high dose (64 g·kg^-1·day^-1) of Zhibai Dihuang decotion groups, positive drug group (alendronate, 9.9 mg·kg^-1·q3d). After modeling, mice were given medication intervention for 8 weeks, and then femoral and tibial tissues were taken to detect indicators such as bone microstructure, bone resorption, and oxidative stress. The experimental results showed that after Zhibai Dihuang decotion administration, the bone microstructure damage caused by OVX surgery was alleviated, and the relevant parameters bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb. N) and connectivity density (Conn. D) both significantly increased. At the same time, the number of TRAP positive osteoclasts decreased significantly, and the levels of proteins and genes related to osteoclast differentiation decreased, indicating that Zhibai Dihuang decoction could inhibit the increased activity of osteoclast caused by OVX. Afterwards, network pharmacology was used to construct the active compound action target network of Zhibai Dihuang decotion, and it was found that the target genes of its active ingredients were closely related to the oxidative stress pathway. Finally, the detection results of oxidative stress levels in bone tissues showed that after treatment with Zhibai Dihuang decotion, the levels of oxidative stress products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) in bone tissues of mice significantly decreased, while the levels of antioxidant stress substance L-glutathione (GSH) increased. These above results indicated that Zhibai Dihuang decotion can regulate the level of oxidative stress in the body and inhibit osteoclast activity, which played a therapeutic role in PMOP, as well as provided theoretical basis for the prevention and treatment of PMOP with traditional Chinese medicine.

Objective:To explore the clinical efficacy of a retrograde pubic ramus intramedullary nail (RPRIN) in the treatment of anterior pelvic ring fractures.Methods:A retrospective study was conducted to analyze the 14 patients with anterior pelvic ring fracture who had been treated and followed up at Department of Traumatic Surgery, Tongji Hospital From June 2020 to February 2021. There were 10 males and 4 females with an age of (44.8±12.5) years. By the AO/OTA classification for pelvic fractures, 5 cases were type 61-A, 4 cases 61-B, and 5 cases type 61-C; by the Nakatani classification, 1 case belonged to unilateral zone Ⅰ fracture, 5 cases to unilateral zone Ⅱ fracture, 2 cases to unilateral zone Ⅲ fracture, 3 cases to right zone Ⅱ and left zone Ⅲ fracture, 2 cases to zone Ⅲ fracture on both left and right sides, and 1 case to zone Ⅱ fracture on both sides. The time from injury to operation was (7.8±1.8) days. All the anterior pelvic ring fractures were fixated with a RPRIN. The time and fluoroscopic frequency for placement of every single RPRIN, quality of fracture reduction, and pelvic function and incidence of postoperative complications at the last follow-up were recorded.Results:A total of 18 RPRINs were placed in the 14 patients. For placement of each RPRIN, the time was (35.9±8.6) min, and the fluoroscopic frequency (22.8±1.9) times. No complications such as infection occurred at any surgical incision after RPRIN placement. According to the Matta scoring, the quality of postoperative fracture reduction was assessed as excellent in 7 cases, as good in 5 cases and as fair in 2 cases. The 14 patients were followed up for (18.1+1.5) months. Their X-ray and CT images of the pelvis at the last follow-up showed that the fractures healed well and the intramedullary nails were placed in the cortical bone of the anterior ring of the pelvis. According to the Majeed scoring at the last follow-up, the pelvic function was assessed as excellent in 10 cases, as good in 3 cases and as fair in 1 case. One patient reported discomfort during squatting 2 months after operation but the symptom improved 3 months later without any special treatment. No patient experienced such complications as displacement or slippage of RPRIN, or pain at the insertion site.Conclusion:RPRIN is effective in the treatment of anterior pelvic ring fractures, showing advantages of small surgical incision, limited intraoperative fluoroscopy and short operation time.