Immune checkpoint inhibitors (ICIs) are widely used in the treatment of malignant tumors, and their related immune-related adverse events (irAEs) have attracted increasing attention. This study reports the diagnosis and treatment process of a case of immune cystitis in a patient with hepatobiliary tract malignant tumor after treatment with pembrolizumab. The patient was admitted to the hospital due to frequent urination, urgency of urination and dysuria for 1 month. Previous repeated anti-infection treatments were ineffective. Combined with medical history, laboratory tests, imaging findings, cystoscopy and pathological results, the patient was clinically diagnosed with ICIs-associated immune cystitis (Pembrolizumab) ultimately. The patient's symptoms significantly improved after treatment with glucocorticoids. This case reindicates that clinicians need to improve awareness of ICI-related urinary system irAEs. Early identification and timely intervention can significantly improve patient prognosis.

ObjectiveThe exacerbating trend of global population aging poses profound socioeconomic and public health challenges, making the comprehensive elucidation of biological aging mechanisms and the discovery of effective anti-aging interventions an urgent priority in the life sciences. Based on our previous serum metabolomics findings that dimethylglycine, an intermediate metabolite of amino acid metabolism naturally present in the human body, was significantly enriched in the serum of longevity families, this study aimed to systematically investigate the anti-aging effects of dimethylglycine both in living organisms and in controlled laboratory environments, and to preliminarily elucidate its underlying molecular mechanisms. While existing literature indicates that dimethylglycine possesses antioxidant and immunomodulatory properties, its direct anti-aging efficacy and the specific molecular pathways through which it operates remain largely unexplored. MethodsTo comprehensively evaluate the anti-aging properties of dimethylglycine, we utilized replicative senescent human embryonic lung fibroblasts, specifically the WI-38 cell line, as an experimental model in a controlled laboratory environment. Cell viability and safety were thoroughly assessed using Cell Counting Kit-8 and lactate dehydrogenase release assays across various concentrations of dimethylglycine. The impact of dimethylglycine on cellular senescence phenotypes, oxidative stress, and proliferative capacity was evaluated via senescence-associated beta-galactosidase staining, reactive oxygen species fluorescence detection, and 5-ethynyl-2'-deoxyuridine incorporation assays. Furthermore, the molecular alterations of senescence-associated secretory phenotype factors and core senescence signaling pathways were quantified using quantitative reverse transcription polymerase chain reaction for the messenger RNA levels of interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1, and enzyme-linked immunosorbent assay for the measurement of p16 and p21 protein expression levels. For the living organism model, the wild-type nematode Caenorhabditis elegans was used to evaluate systemic physiological effects. We conducted a comprehensive lifespan analysis at 20°C, heat stress resistance survival assays at 35℃, senescence-associated beta-galactosidase staining, lipofuscin accumulation tracking, intracellular reactive oxygen species measurement, and Oil Red O staining to ascertain systemic lipid accumulation. Additionally, network pharmacology bioinformatics tools, including PharmMapper and STRING databases, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were utilized to predict target pathways, alongside highly detailed molecular docking simulations utilizing SwissDock and Protein-Ligand Interaction Profiler to examine interactions with the cytochrome P450 family 2 subfamily C member 9 protein. ResultsThe experimental outcomes robustly demonstrate the potent anti-aging capabilities of dimethylglycine. At the cellular level, toxicity analyses firmly confirmed that dimethylglycine is highly safe; continuous treatment with 50 mol/L and 70 mol/L of dimethylglycine for 5 d did not induce any cellular membrane damage or cytotoxicity, but rather actively promoted cellular proliferation. Utilizing the optimal standardized concentration of 50 mol/L, dimethylglycine treatment significantly ameliorated senescent phenotypic markers in human embryonic lung fibroblasts, which was evidenced by a drastic and highly significant reduction in the senescence-associated beta-galactosidase positive cell percentage (P<0.000 1) and intracellular reactive oxygen species levels (P<0.000 1), alongside a marked increase in the 5-ethynyl-2'-deoxyuridine-positive proliferation rate (P=0.003 5). On a molecular expression scale, dimethylglycine significantly downregulated the messenger RNA expression of multiple core senescence-associated secretory phenotype inflammatory factors, including interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1. Concurrently, it effectively suppressed the protein expression of critical cell cycle arrest markers, diminishing p16 protein levels by 57.3% (P=0.000 4) and p21 protein levels by 27.2% (P=0.000 7). In the nematode Caenorhabditis elegans animal model, dimethylglycine significantly extended the mean lifespan from 20.402 d to an impressive 23.066 d (P<0.000 1) and notably enhanced overall survival rates under severe heat stress environmental conditions (P=0.017). Furthermore, systemic dimethylglycine intervention significantly mitigated age-related physiological decline by decreasing bodily lipofuscin accumulation (P<0.000 1), significantly reducing senescence-associated beta-galactosidase activity, lowering systemic reactive oxygen species fluorescence (P=0.008), and effectively alleviating overall fat accumulation (P<0.000 1). Mechanistically, extensive network pharmacology and Kyoto Encyclopedia of Genes and Genomes analyses strongly revealed that the potential targets of dimethylglycine are significantly enriched in fundamental drug metabolism and oxidative stress response pathways. Precision molecular docking simulations conclusively demonstrated that dimethylglycine forms highly stable structural interactions with the cytochrome P450 family 2 subfamily C member 9 protein, specifically highlighting the definitive formation of 5 stable hydrogen bonds involving serine 365, leucine 366, and serine 429 residues, as well as two critical salt bridge formations with arginine 97 and histidine 368 residues. It is additionally predicted to interact favorably with glutathione S-transferase family proteins. ConclusionDimethylglycine exhibits a profoundly significant and multifaceted anti-aging activity at both the cellular and entire living animal levels. By powerfully alleviating oxidative stress, heavily suppressing the core p16 and p21-dependent cellular senescence signaling pathways, and substantially mitigating the detrimental senescence-associated secretory phenotype, dimethylglycine effectively delays fundamental cellular senescence processes and drastically extends whole-organism lifespan. The biological mechanisms driving these robust protective effects are highly likely closely associated with its direct stable interactions with crucial metabolic and detoxifying enzyme systems, such as cytochrome P450 family 2 subfamily C member 9 and glutathione S-transferase family proteins, thereby systemically improving metabolic dysregulation and restoring critical redox homeostasis. This comprehensive study provides highly solid experimental evidence supporting dimethylglycine as a highly potent and safe potential anti-aging intervention agent, while simultaneously offering a clear molecular mechanistic explanation for the previously documented high abundance of dimethylglycine observed within exceptionally long-lived human populations.

Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

Hygroscopicity research has long been a key focus and hot topic in Chinese materia medica（CMM）. Elucidating hygroscopic mechanisms plays a vital role in formulation design， process optimization， and storage condition selection. Hygroscopic models serve as essential tools for characterizing CMM hygroscopic mechanisms， with various types available. The double exponential model is a kinetic mathematical model constructed based on the law of conservation of energy and Fick's first law of diffusion， tailored to the physical properties of CMM extracts. In recent years， this model has been extensively applied to simulate the dynamic moisture absorption behavior of CMM extracts and solid dosage forms under varying humidity conditions. It has revealed the correlation between moisture absorption kinetic parameters and material properties， offering a new perspective for characterizing the moisture uptake behavior of CMM. This paper systematically reviews the application progress of this model in the field of CMM， analyzes its advantages， disadvantages， and challenges in this domain， and explores its potential application trends in other fields. It aims to provide references for elucidating the moisture absorption mechanisms of CMM and researching moisture-proofing technologies， while also offering insights for its broader application in food and polymer materials.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective To design an 8-channel gene analyzer to take the place of the widely used gene analyzer with problems in inconvenient consumable replacement and short storage time of electrophoresis polymer.Methods The 8-channel gene analyzer had its mechanical components composed of an automatic sample loading table,a polymer injection module,a high-voltage temperature control module,an optical module and an integrated U box,its electrical control system made up of a host computer(an embedded computer)and three slave computers(a sampling control board,a polymer injection control board and a high-voltage temperature control board).The automatic sample loading table involved in four motors and transmission systems for x,y,z directions and optical alignment,the transmission systems adopted mainly belt drive mode and the optical alignment motor had its threads with an anti-backlash structure;the polymer injuection module was manipulated by the polymer injection control board,and the polymer block was made of highly transparent acrylic material;the high-voltage temperature control module realized the regulation of electrophoresis voltage and the detection of electrophoresis current by the low-ripple precision high-voltage power supply,and controlled the temperature of the heating furnace by the proportional-integral-differential(PID)algorithm;the optical module consisted of an excitation module and a light-receiving module,which had the base of the reflector made of low expansion coefficient alloy material;the integrated U box had the electrophoresis polymer,capillary array,polymer block and anode buffer in a plastic housing;the host computer had the data acquisition software programmed with C# and C++,and the slave computers were controlled by STM32 SCM.Results The 8-channel gene analyzer had no significant differences with the widely used ABI3500 gene analyzer in resolution,precision accuracy and clinical results.Conclusion The 8-channel gene analyzer gains advantages in consumable replacement and storage time of electrophoresis polymer,and can meet the requirements for gene sequencing.[Chinese Medical Equipment Journal,2025,46(2):24-30]

The incidence of non-alcoholic fatty liver disease(NAFLD)has been increasing annually.Current primary treatment strategies involve dietary modifications and increased physical activity to allevi-ate symptoms,yet there is a notable lack of targeted pharmacological interventions.Members of the micro RNA-29(miR-29)family(miR-29a,miR-29b,miR-29c)are known to play a critical regulatory role in lipid metabolism within hepatocytes;however,the underlying mechanisms remain to be elucidated.This study aims to identify the target genes and associated signaling pathways of the miR-29 family,thereby providing potential therapeutic targets for the development of NAFLD treatments.Firstly,the human liver cell line HepG2 was utilized as a model for adipogenic induction,and miR-29a/b/c-3p mimics were indi-vidually transfected.Through methods such as Oil Red O staining and triglyceride(TG)quantification,it was observed that the miR-29 family members significantly inhibited lipid accumulation in hepatocytes(P＜0.05).Subsequently,qRT-PCR and Western blot were utilized to detect the expression levels of ad-ipogenic marker genes(fatty acid synthase(FAS),acetyl coa carboxylase(ACACA),stearoyl-coen-zyme a desaturase 1(Scd 1))and autophagy marker genes(sequestosome 1(SQSTM1,also known as p62),autophagy related gene 5(Atg5)),and the results indicated that the members of the miR-29 fam-ily could significantly suppress the expression of FAS,ACACA,Scd1,and p62 genes in hepatocytes,while significantly enhancing the level of the Atg5 gene.Further investigations using signaling pathway activity analysis and dual luciferase reporter assays confirmed that the miR-29a/b/c could suppress the mTOR signaling pathway activity and directly interact with the ten-eleven translocation 2(TET2)gene.Finally,co-transfection experiments were performed to examine the potential synergistic effects among the miR-29-3p family members,and the results demonstrated that co-transfection of miR-29 family members more effectively inhibited lipid droplet accumulation in HepG2 cells and further suppressed the expression of the target gene TET2 compared to individual transfection.In summary,the miR-29 family members may reduce lipid accumulation in hepatocytes by inhibiting the mTOR signaling pathway via the TET2 gene,and they exhibit a positive synergistic effect.

Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

Objective:The purpose of this study is to explore the influencing factors of poor prognosis in henoch-schonlein purpura(HSP)children,and to construct a nomogram model and verify its validity through the analysis results of Logistic regression model.Methods:Collected the clinical data of 170 HSP children who were treated in Fuzhou Luoyuan County Hospital from January 2015 to May 2023 were retrospectively analyzed.They were divided into good prognosis group and poor prognosis group according to the prognosis after treatment.The clinical data and related biochemical indexes of different prognostic groups were compared.The factors of poor prognosis in HSP children were analyzed by Logistic regression model.A predictive model(nomogram)for poor prognosis in HSP children were constructed and evaluated its predictive performance.Prediction accuracy were evaluateed by receiver operating characteristic(ROC)curve.Results:170 HSP children,69 cases(40.59％)had poor prognosis and 101 cases(59.41％)had good prognosis.C-reactive protein(CRP),kidney injury at initial onset,platelet count(PLT),respiratory infection,recurrent rash,and immunoglobulin A(IgA)levels in poor prognosis group were higher than those in good prognosis group(P＜0.05).Multivariate logistic analysis showed that,recurrent rash,respiratory infection,elevated PLT,CRP and IgA levels were independent influencing factors of poor prognosis in HSP children(P＜0.05).The consistency index(C-index)of the column chart model established based on the results of multiple factor analysis was 0.798.The internal verification was carried out by Bootstrap self-sampling method,and the average absolute error of calibration curve was 0.017.ROC curve was drawn according to independent influencing factors and nomogram prediction probability,the area under the curve was 0.674(recurrent rash),0.649(respiratory infection),0.777(PLT),0.733(CRP),0.749(IgA)and 0.910(nomogram prediction probability)respectively.Conclusion:Recurrent rash,respiratory infection,PLT,CRP and IgA are independent factors affecting the prognosis of HSP children.The column chart prediction model constructed based on the above factors has certain predictive value for the poor prognosis in HSP children.