ObjectiveTo investigate the effects of retention enema with Huangling Jiedu Xiezhuo granules（HJXG） on Nod-like receptor protein 3（NLRP3）， intestinal flora， and short-term prognosis in patients with gout. MethodsA total of 60 patients with gout admitted to the hospital from January 2021 to December 2023 were selected and divided into a control group and an observation group according to the random number table method， with 30 cases in each group. The control group was treated with febuxostat， and the observation group was treated with retention enema with HJXG on the basis of the control group. After 14 days of continuous treatment， the clinical efficacy， traditional Chinese medicine （TCM） syndrome score， and visual analogue scale （VAS） pain index of the two groups were compared， and serum creatinine（SCr）， blood urea nitrogen（BUN）， uric acid（UA）， cystatin C（CysC）， β₂- microglobulin（β₂-MG）， glomerular filtration rate test（GFR）， creatinine clearance rate （Ccr）， erythrocyte sedimentation rate（ESR）， hypersensitive C-reactive protein，（hs-CRP）， interleukin 6（IL-6）， interleukin-1β（IL-1β）， interleukin-18 （IL-18）， NLRP3 inflammasome levels， and the number of intestinal flora were detected in the two groups. The prognosis of patients was followed up within 12 weeks. COX regression analysis was used to analyze the effect of short-term prognosis. ResultsAfter treatment， TCM syndrome scores and VAS pain index in both groups were reduced （P<0.05）， and TCM syndrome scores in the observation group were significantly lower than those in the control group. After treatment， ESR， hs-CRP， IL-6， NLRP3， IL-18， and IL-1β were significantly decreased in both groups （P<0.01）， and the levels of IL-6， ESR， NLRP3， and IL-18 were significantly improved in the observation group compared with the control group （P<0.05）. BUN， SCr， UA， β₂-MG， GFR indexes in both groups were significantly lower after treatment， Ccr indexes in both groups were significantly higher after treatment， and the levels of SCr， UA， CysC， and Ccr in the observation group were significantly better than those in the control group （P<0.05）. After treatment， the intestinal flora in both groups was improved， and the observation group was significantly improved compared with the control group in terms of Lactobacillus， Proteus， Bacteroides， and Escherichia coli （P<0.05）. COX regression analysis showed that retention enema with HJXG could reduce the risk of poor short-term prognosis in patients with gout compared with Western medicine alone. ConclusionThe retention enema with HJXG can improve the curative effect of patients with gout， improve the TCM syndromes， reduce inflammation， and enhance renal function， intestinal flora， and short-term prognosis.

ObjectiveTo investigate the effects of Xinfeng capsules combined with chronic disease management of traditional Chinese medicine （TCM） on rapid disease control and short-term prognosis of patients with rheumatoid arthritis （RA）. MethodsA total of 80 RA patients hospitalized in the Department of Rheumatology of The First Affiliated Hospital of Anhui University of Chinese Medicine from January 2022 to March 2024 were enrolled and randomly divided into an observation group （40 cases） and a control group （40 cases）. The control group was treated with conventional methotrexate combined with standard chronic disease management， while the observation group was additionally treated with Xinfeng Capsules combined with TCM chronic disease management. The treatment course lasted 24 weeks. The outcomes were compared between two groups， including disease activity ［28-joint disease activity score （DAS28）， clinical disease activity index （CDAI）， simplified disease activity index （SDAI）］， visual analogue scale （VAS） for pain， TCM syndrome score， tender joint count （TJC）， swollen joint count （SJC）， morning stiffness duration， Health Assessment Questionnaire （HAQ）， Self-Rating Anxiety Scale （SAS）， Self-Rating Depression Scale （SDS）， American College of Rheumatology （ACR） 20%， 50% and 70% response rates （ACR20/50/70）， erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide antibody （CCP-Ab）， interleukin （IL）-6， IL-1β， tumor necrosis factor-α （TNF-α）， and serum immunoglobulin G （IgG）. The Chronic Disease Self-Management Scale （CDSMS） was used to evaluate patients’ self-management ability， self-care ability， and nursing satisfaction. Patients were followed up for 12 weeks to assess prognosis， and COX regression analysis was performed to determine the impact on short-term prognosis. ResultsAfter treatment， TJC， SJC， morning stiffness duration， DAS28， CDAI， SDAI， VAS， TCM syndrome score， ESR， hs-CRP， RF， CCP-Ab， IL-6， IL-1β， TNF-α， IgG， HAQ， SAS， SDS， chronic disease self-management behavior， self-efficacy， and self-care ability all improved significantly in both groups compared with baseline （P<0.05，P<0.01）. Compared with the control group， the observation group showed more significant improvements in TJC， SJC， morning stiffness duration， DAS28， CDAI， SDAI， VAS， TCM syndrome score， ESR， IL-1β， IgG， HAQ， SAS， SDS， self-care ability， chronic disease self-management behavior， and self-efficacy （P<0.05 or P<0.01）. The ACR70 response rate and nursing satisfaction were significantly higher in the observation group than in the control group （P<0.01）. COX regression analysis showed that Xinfeng capsules combined with TCM chronic disease management reduced the risk of poor short-term prognosis in RA patients. ConclusionXinfeng capsules combined with TCM chronic disease management facilitates rapid disease control in RA patients， effectively improves short-term prognosis， and plays an important role in the treatment of the disease.

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Objective To develop a machine learning(ML)-based prediction model for assessing the therapeutic effects of resveratrol(RES)on the pathological damage of acute pancreatitis(AP),and to optimize RES administration strategies for AP through validation using an animal model.Methods AAn ML-based prediction model was constructed using published data.Interpretability analysis was applied to identify high-efficacy zones within the parameter space of administration dose and frequency,which was followed by rigorous screening to select the optimal dosing strategy that balanced therapeutic efficacy and experimental feasibility.A total of 32 C57BL/6 mice were randomly assigned to 4 groups(n=8 per group),including a control group(Ctrl),an AP model group induced by caerulein(CER)and referred to as CER-AP,a treatment group receiving RES via intraperitoneal injection(RES i.p.),and a treatment group receiving RES via intragastric gavage(RES i.g.).The Ctrl group received intraperitoneal injection of normal saline.The CER-AP and the treatment groups were induced with 10 intraperitoneal injections of CER at 50 μg/kg.RES was administered to the RES i.p.and RES i.g.groups according to the optimal dose and timing predicted by the ML model.Blood and tissue samples were collected 12 hours after the experiment started.Results The gradient boosting decision tree model,optimized via Hyperopt,yielded the best performance,predicting that the optimal dose and administration frequency were 19.992 mg/kg and 3.828 times,respectively.Accordingly,a regimen of 20 mg/kg RES,administered four times,was used in the animal experiments.Compared with the Ctrl group,the CER-AP group exhibited higher pancreatic pathology scores and elevated levels of serum amylase,lipase,pancreatic myeloperoxidase,and trypsin,with all differences reaching statistical significance(all P<0.05).The administration of 20 mg/kg RES via both intraperitoneal injection and intragastric gavage mitigated pancreatic inflammatory cell infiltration and necrosis,improved the overall pathology score,and reduced serum amylase,lipase,and pancreatic myeloperoxidase levels to varying degrees(all P<0.05).Conclusion A regimen of 20 mg/kg RES administered four times effectively alleviates the severity of CER-induced AP.The therapeutic benefits appear to arise from a multi-target regulatory network that simultaneously suppresses inflammatory cascades,mitigates oxidative stress,and reduces apoptosis,thereby reducing pancreatic tissue damage and systemic inflammatory responses.

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with X-linked cardiac valve dysplasia (CVDPX) and congenital chronic pseudo intestinal obstruction (CIIPX). METHODS: A pedigree presented at the First Hospital of Lanzhou University for CVDPX combined with CIIX was selected as the study subject. Whole exome sequencing (Trio-WES) was carried out, and the candidate variant was verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the First Hospital of Lanzhou University (Ethics No. LDYYSZLLKH2024-15). RESULTS: Both the proband and his affected younger brother were found to harbor a hemizygous c.443A>G (p.Tyr148Cys) variant of the FLNA gene, for which their mother was heterozygous and their father was not a carrier, suggesting an X-linked recessive inheritance pattern. The variant was not recorded in the OMIM and ClinVar databases, and was determined to be likely pathogenic (PM2+PS4+PP2+PP3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The patients had presented with typical CVDPX/CIIPX phenotype, including multiple valve dysplasia and chronic pseudo intestinal obstruction, in addition with gallbladder wall edema and thickening. Bioinformatic analysis showed that the variant site is highly conserved, and multiple algorithms had predicted its pathogenicity. CONCLUSION This study confirmed the diagnosis of CVDPX/CIIX in a Chinese pedigree, expanded the phenotype spectrum of FLNA gene variants, and provided a basis for genetic counseling and prenatal diagnosis for the pedigree.
Adult ; Female ; Humans ; Male ; Exome Sequencing ; Filamins/genetics* ; Genetic Diseases, X-Linked/genetics* ; Heart Defects, Congenital/genetics* ; Heart Valve Diseases/genetics* ; Pedigree ; East Asian People/genetics*

Clinical pharmacists participated in the anti-infection treatment of a patient with Bartonella henselae meningitis.According to the clinical manifestations and the quantitative metagenomic second-generation sequencing(mNGS)of cerebrospinal fluid,the patient was diagnosed as Bartonella henselae infection.According to the relevant clinical guidelines and foreign case treatment reports,it is recommended to use minocycline hydrochloride capsule oral treatment combined with rifampicin injection.Follow-up treatment of the patient was dynamically adjusted based on the reexamination results of cerebrospinal fluid and related inflammatory indicators.In the treatment process,clinical pharmacists give full play to their professional expertise,provide the patient with individualized pharmaceutical care,optimize anti-infection programs,and further promote clinical rational drug use.

Cardiovascular disease is a health hazard to humans and systolic heart failure due to myocardial infarction is a major cause of death.It was previously thought that myocardial cells of the adult mammalian heart possess a limited ability to proliferate and self-renew.However,it has been widely reported that mammals have the ability to regenerate the myocardium,which is restricted to early postnatal life,and that it is strong enough to repair damaged heart tissue.The discovery of myocardial regeneration in neonatal hearts has provided an ideal animal model to investigate the mechanisms that affect myocardial regeneration,and many mechanisms that reverse myocardial cell cycle arrest and promote myocardial regeneration have been revealed.In this article,we review the factors affecting gene expression for myocardial regeneration(e.g.,ncRNAs and transcription factors),myocardial regeneration-related signaling pathways,and the regulation of myocardial regeneration by non-myocardial cells(e.g.,extracellular matrix,immune response,and epicardium)to provide directions for achieving myocardial regeneration after myocardial injury in adult mammals.

Objective:To compare clinical characteristics,treatment patterns and physiological indicators in bipolar disorder(BD)patients with different age of onset.Methods:Totally 380 patients with DSM-5 BD were se-lected in this study.Psychiatrists diagnosed the patients using the Mini International Neuropsychiatric Interview.The clinical information questionnaire and the Global Assessment of Functioning scale were utilized to collected clinical characteristics,treatment status,and physiological indicators.The onset age of BD was divided into 21 and 35 years as cut-off points.Multivariate logistic regression and linear regression were used to analyze related factors.Results:Among the 380 patients with BD,199 cases were early-onset group(52.4％),121 cases were middle-onset group(31.8％),and 60 cases were late-onset group(15.8％).There were 26.6％of patients in the early-onset group in-itially diagnosed as depression,23.1％in the middle-onset group,and 11.7％in the late-onset group.Multivariate analysis revealed that compared to the early-onset group of BD,the middle-onset(OR=2.22)and late-onset(OR=4.99)groups had more risk to experience depressive episodes,and the late-onset group(OR=6.74)had 6.74 times of risk to suffer from bipolar Ⅱ disorder.Additionally,patients in the middle-onset(β=-1.52)and late-on-set(β=-4.29)groups had shorter durations of delayed treatment,and those in the middle-onset(β=-1.62)and late-onset(β=-3.14)groups had fewer hospitalizations.Uric acid levels were lower in both the middle-onset(β=-28.39)and late-onset(β=-31.47)groups,and total cholesterol level was lower in the middle-onset group(β=-0.23).Conclusion:Patients with BD in different age of onset show significant differences in clinical charac-teristics,treatment conditions and physiological indicators.