ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

OBJECTIVE To establish a Chinese drug-related problem （DRP） classification system applicable to pharmacist-led pharmaceutical care in China， providing pharmacists with an effective and practical tool for pharmaceutical care. METHODS A multi-stage process was employed to construct the DRP classification system， including literature review and analysis， comparison of existing classification systems， refinement of classification items and framework development， two rounds of standard case validation， expert discussion， and system revision. The Fleiss′ kappa test was used to calculate the consistency coefficient κ， assessing the reliability of pharmacists participating in evaluating the classification system. An electronic questionnaire comprising six items was employed to evaluate the system’s applicability. RESULTS The constructed Chinese DRP classification system comprised six sections [problem（including potential problems）， DRP evaluation， cause （including possible causes of potential problems）， intervention， acceptance of intervention and DRP status]， with 24 primary codes and 96 secondary codes. In the first round of case validation， κ values exceeded 0.4 for all sections except “intervention” and “DRP status”. In the second round， κ values exceeded 0.4 for all sections. In the applicability evaluation of the classification system， positive ratings （“strongly agree” or “agree”） exceeded 85% for all items. Specifically， positive ratings for“the classification system can provide appropriate category selection”，“ the classification system is comprehensive”，“ the classification system is convenient to use” and “the classification system is highly satisfactory” exceeded 92%. CONCLUSIONS The Chinese DRP classification system developed demonstrates both high reliability and applicability， providing an effective and practical classification tool for pharmacists in China to conduct pharmaceutical care.

Fresh-cut processing constitutes a pivotal technique in the origin processing of Chinese medicinal materials， with a long history documented in multiple materia medica. In recent years， it has garnered national policy support for its ability to prevent component loss and low processing efficiency associated with traditional drying-before-cutting methods. As of August 2025， 26 provinces and municipalities nationwide have cumulatively published 789 species for fresh-cut processing. Among these， 78 were included in the 2025 edition of the Pharmacopoeia of the People's Republic of China. However， the practice continues to face common challenges and difficulties， including ambiguous scientific understanding， fragmented standards， limited quality control approaches， and poor process stability. Based on this， this paper synthesises years of research findings to systematically elucidate the core mechanisms of fresh-cut processing. These encompass alterations to herbal tissue structure during cutting， post-processing changes in constituents， and physiological-biochemical processes such as plant stress responses and shifts in endogenous enzyme activity. It also summarises influencing factors， including inherent herbal properties， cutting timing and methods， and environmental conditions like temperature， humidity， and microbial presence. Based on this overview of fresh-cutting mechanisms， subsequent research should advance in four directions：Clarifying the scientific principles of fresh-cutting， overcoming technical bottlenecks， upgrading intelligent equipment， and establishing quality standards and evaluation systems. This study provides a theoretical foundation and scientific basis for future research on fresh-cutting in traditional Chinese medicine（TCM）， promoting its deeper practical application within the industry and contributing to the high-quality development of TCM industry and the modernization of TCM.

Methods: This retrospective cohort study included 153 single-level OLIF cases between January 2016 and December 2023. Postoperative computed tomography was used to classify patients into central fusion, lateral fusion, and non-fusion groups. Demographic, surgical, and radiographic parameters—including osteophyte grade, Hounsfield unit (HU) values, and cage positioning—were analyzed to identify factors affecting fusion. Cage subsidence and clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale) were compared across groups. Results: Lateral fusion occurred in 39.9% of cases, central in 56.9%, and non-fusion in 3.2%. Preoperative osteophytes and higher HU values were associated with lateral fusion (p<0.001). OLIF with standalone cages (OLIF-SA) had a significantly higher lateral fusion rate than OLIF with posterior screw fixation (OLIF-PS) (p=0.002). Smoking was a significant risk factor for non-fusion (p=0.005). No significant difference in cage subsidence was observed between central and lateral fusion, but non-fusion showed more severe subsidence. Clinical outcomes improved across fusion groups, though non-fusion cases had worse ODI scores at follow-up. Conclusions Lateral fusion is a distinct OLIF feature influenced by osteophytes, bone density, and fixation type. It does not negatively affect cage subsidence or outcomes, but solid fusion remains essential for recovery. These findings enhance understanding of OLIF fusion and may guide surgical planning.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Objective To investigate the etiology and treatment of dysuria shortly after holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia (BPH), so as to improve the therapeutic efficacy. Methods A retrospective analysis was conducted on 1361 BPH patients who received HoLEP at our hospital during Mar. 2018 and Mar. 2025. All patients underwent ultrasound, computed tomography (CT), urethral probing or radiography, cystourethroscopy, and urodynamic testing. The causes, treatments and prognosis of dysuria after operation were summarized. Results ninety-eight patients (7.2%) experienced dysuria within 3 months after surgery, and all patients received initial urethral dilation. Among the 62 cases with urethral stricture, 28 were treated with urethral dilation (average of 8 sessions), 16 underwent external urethral incision, 8 underwent anterior urethroplasty, and 10 underwent transurethral plasma incision for urethral stricture. Of the 12 cases with residual prostate tissue, 5 underwent urethral plasma prostatectomy and 7 received medication. All of the 12 cases with bladder neck contracture underwent transurethral plasma incision of the bladder neck and local drug injection. Five cases with intravesical blood clots underwent urethral blood clot irrigation, 2 of which developed active bleeding and then underwent electrocoagulation. Four cases with detrusor dysfunction had catheters re-indwelled for one week followed by medication. Two cases with stone and one case with tissue fragment impacted in the urethra underwent urethral holmium lithotripsy and cystoscopic removal. All patients underwent reoperation successfully and experienced complete resolution or significant improvement of urinary difficulties. Conclusion A certain proportion of patients experience dysuria after HoLEP, with diverse etiologies. The combination of prevention and treatment can reduce the incidence of dysuria.

ObjectiveTo explore the ameliorative effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid （4-PBA） on bile acid metabolism disorders induced by bacterial lipopolysaccharide （LPS） in late-pregnant mice， and to clarify the regulatory mechanism of endoplasmic reticulum stress （ERS） in intrahepatic cholestasis of pregnancy （ICP）. MethodsTwenty-four pregnant mice were divided into control group， LPS group， 4-PBA group， and LPS+4-PBA group. On the 16th day of pregnancy， the LPS group received intraperitoneal injection of LPS （200 μg/kg） and the 4-PBA group received injection of 4-PBA （150 mg/kg）. In the LPS+4-PBA group， 4-PBA was intraperitoneally injected first， followed by LPS administration 1 h later. Serum total bile acid （TBA）， liver injury markers， bile acid profiles， and the expression of key genes and proteins were detected 6 h after LPS treatment. ResultsLPS exposure increased serum TBA levels in pregnant mice（P<0.05）， activated ERS markers and inflammatory factors， and downregulated bile acid transporters and the expression of the rate limiting enzyme CYP7A1（all P<0.05）. 4-PBA intervention effectively inhibited ERS， reduced TBA levels（P<0.05）， and upregulated Ntcp， Bsep， Mdr3， and Mrp3 gene expression（all P<0.05）. ConclusionERS plays an important role in LPS interference with the homeostasis of bile acid metabolism during pregnancy. Inhibiting ERS can improve bile stasis by regulating bile acid transporters， providing a theoretical basis for targeted therapy of ICP.

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Objective:To investigate the effect of advanced glycation end products (AGEs) on ferroptosis in human retinal pigment epithelium (RPE) cell cultured in vitro. Methods:ARPE-19 cell lines were cultured in DMEM medium containing 10% fetal bovine serum (FBS), and the 3rd to 6th generations of cells were used for further study.Cell activity was detected by using the cell counting kit 8 after ARPE-19 were cultured with AGEs at 0, 50, 100, 200, 400 μg/ml for 48 hours.The cells were cultured with 200 μg/ml AGEs for 48 hours.Cell lipid peroxidation level was measured by Lipid Peroxidation Assay Kit (Bodipy 581/591 C11) combined with flow cytometry.The relative mRNA and protein expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were determined by quantitative real-time PCR (qRT-PCR) and Western blot.The morphology of mitochondria was observed by transmission electron microscope.Results:The activity of ARPE-19 cells decreased with increasing AGEs concentration, and the overall difference of ARPE-19 activity among 0, 50, 100, 200, 400 μg/ml AGEs groups was statistically significant ( F=6.21, P<0.01).The cell activity of ARPE-19 cells in 200 and 400 μg/ml AGEs groups was lower than that in control group (both P<0.05).Flow cytometry showed that the fluorescence intensity in AGEs group was 622.0±11.3, which was significantly higher than 487.7±12.8 in control group ( t=6.809, P=0.002).qRT-PCR showed that the mRNA and protein relative expression levels of SLC7A11 and GPX4 were lower in AGEs group than those in control group (mRNA: t=3.72, 7.14, both P<0.05; protein: t=6.20, 5.15, both P<0.05).Transmission electron microscopy showed that mitochondria in AGEs group shrank with significantly reduced volume, decreased mitochondrial cristae, and increased mitochondrial membrane density. Conclusions:AGEs can induce ferroptosis in ARPE-19 cultured in vitro.

Objective To investigate the effect of closed-chain exercise training on hemiplegic shoulder pain and shoulder joint sta-bility in stroke patients,and to explore the relationship between hemiplegic shoulder pain and shoulder joint sta-bility.Methods A total of 52 stroke patients with hemiplegic shoulder pain in Jiangsu Province Hospital from October,2020 to January,2023 were selected,and were randomly divided into control group(n=26)and experimental group(n=26).Both groups received conventional rehabilitation therapy,while the experimental group additionally under-went closed-chain exercise training for shoulder joint.Pain severity and motor function were assessed using Visu-al Analog Scale(VAS)and Fugl-Meyer Assessment-Upper Extremities(FMA-UE)before and after intervention.Musculoskeletal ultrasound was used to measure acromion-greater tuberosity distance(AGT),acromion-lesser tu-berosity distance(ALT),acromiohumeral distance(AHD)and supraspinatus thickness(SST)to evaluate shoulder joint stability.Correlation analysis was conducted on the improvements in shoulder pain and shoulder joint stabil-ity in the experimental group.Results Two cases in the control group and two in the experimental group dropped down.Both groups showed signifi-cant improvements in VAS and FMA-UE scores after intervention(|t|>5.214,P<0.001),and the scores im-proved more in the experimental group than in the control group(|t|>2.087,P<0.05).The experimental group also showed significant improvements in AGT,ALT,AHD and SST(|t|>4.187,P<0.001),with AGT,ALT and AHD being superior to those in the control group(|t|>2.155,P<0.05).The difference of VAS score in the exper-imental group was correlated with the difference of FMA-UE,AGT and ALT after intervention(r>0.434,P<0.05).Conclusion Closed-chain shoulder exercise training can significantly improve shoulder joint stability while alleviating shoulder pain,and effectively enhancing upper limb function in stroke patients with hemiplegic shoulder pain.Hemiplegic shoulder pain is correlated with shoulder joint stability.