Objective: To investigate the mechanism of action of Prim-O-glucosylcimifugin (POG) to improve cholesterol metabolism in osteoarthritic (OA) chondrocytes based on the long noncoding RNA nuclear-enriched transcript 1 (lncRNA NEAT1)/microRNA-128-3p (miR-128-3p) pathway. Methods: For in vivo experiments, 60 mice were divided into the normal, sham operation, model, and POG groups using the random number table method, with 15 mice per group. The osteoarthritis mouse model was constructed using the modified Hulth method in the model and POG groups. Mice in the POG group were administered 30 mg/(kg·d)POG by gavage. The other groups were administered an equal amount of normal saline for 8 weeks. The cartilage tissue structure of mice in each group was observed using hematoxylin and eosin staining. Real-time PCR was used to detect changes in the lncRNA NEAT1 and miR-128-3p mRNA expression levels in the cartilage tissues of mice. Western blotting was used to detect the protein expressions of ATP-binding cassette transporter A1 (ABCA1), liver X receptor β (LXRβ), matrix metalloprotein-3 (MMP-3), and B-lymphoblastoma-2-associated X protein (Bax) in articular cartilage of mice. An enzyme-linked immunosorbent assay was used to measure the tumor necrosis factor-α (TNF-α) content in the synovial fluid of mice. A biochemical microplate assay was used to measure the total cholesterol level in the synovial fluid of mice. The in vitro experiments were divided into the negative control, interleukin-1β(IL-1β), IL-1β+ POG, IL-1β+ oe-lncRNA NEAT1, IL-1β+ oe-lncRNA NEAT1 + POG, IL-1β + miR-128-3p inhibition, and IL-1β+ miR-128-3p inhibition+ POG groups. An OA model was established by inducing chondrocytes with IL-1β for 24 h, and 90 mg/L of POG and miR-128-3p inhibitor(50 nmol/L) were administered for 48 h as an intervention. lncRNA NEAT1 expression in chondrocytes was detected using fluorescence in situ hybridization. A dual luciferase assay was used to detect the targeting relationship between lncRNA NEAT1 and miR-128-3p. Lentiviral plasmids overexpressing lncRNA NEAT1 were used to transfect mouse chondrocytes. Real-time PCR was used to detect the effect of lncRNA NEAT1 overexpression on the mRNA level of miR-128-3p in chondrocytes. Western blotting was used to detect ABCA1, LXRβ, MMP-3, and Bax protein expression in chondrocytes after lncRNA NEAT1 overexpression and miR-128-3p inhibition. Results: POG significantly reduced OA cartilage tissue damage. Compared with the model group, the lncRNA NEAT1 mRNA level decreased, whereas the miR-128-3p mRNA level increased in the cartilage tissue of the POG group (P<0.05). Compared with the model group, ABCA1 and LXRβ protein expression increased in the POG group, whereas MMP-3 and Bax protein expression decreased (P<0.05). The TNF-α levels decreased in the POG group compared to the model group (P<0.05). Compared with the model group, the total cholesterol level in the synovial fluid of the joint of mice in the POG group decreased (P<0.05). The mean fluorescence intensity of lncRNA NEAT1 in the IL-1β+ POG group decreased compared with the IL-1β group (P<0.05). The relative luciferase activity in the miR-128-3p mimics group bound to the lncRNA NEAT1-WT plasmid decreased compared with the miR-128-3p negative control group (P<0.05). The lncRNA NEAT1 mRNA levels decreased, whereas the miR-128-3p mRNA levels increased in the IL-1β+ oe-lncRNA NEAT1 + POG group compared with the IL-1β+ oe-lncRNA NEAT1 group (P<0.05). Compared with the IL-1β+ POG group, ABCA1 and LXRβ protein expression decreased, whereas MMP-3 and Bax protein expression increased (P<0.05). Conclusion POG mediates lncRNA NEAT1/miR-128-3p to improve cholesterol metabolism in OA chondrocytes.

[Objective] To explore the safety and efficacy of submucosal injection of glycerol and fructose saline in bladder tumor endoscopic submucosal dissection (BT-ESD) with a 450 nm blue laser semiconductor treatment machine in the treatment of non-muscular invasive bladder cancer (NMIBC). [Methods] Clinical data of 20 patients with bladder tumor treated with submucosal injection of glycerol and fructose saline BT-ESD via a 450 nm blue laser semiconductor treatment machine at our hospital during Nov.2023 and Apr.2024 were retrospectively analyzed.The patients included 13 males and 7 females, aged (64.95±6.89) years, tumor diameter (1.02±0.24) cm, and preoperative hemoglobin (Hb) (130.55±4.36) g/L.The operation time, Hb the next day after operation, positive rate of tumor basal biopsy, postoperative bladder irrigation time, catheter indwelling time, postoperative hospital stay, complications and recurrence rate were recorded. [Results] All operations were successful, and 28 lesions were removed.The postoperative pathological results confirmed that all cases were NMIBC, and the basal mucosa biopsies were negative.The operation time was (9.40±3.14) min, postoperative Hb (130.15±4.59) g/L, bladder irrigation time (17.70±1.34) h, catheter indwelling time 1 day, and postoperative hospital stay 1 day.There were no complications such as obturator nerve reflex, bladder perforation.There were no need for blood transfusion, no conversion to open surgery, and no secondary bleeding after operation.No tumor recurrence was found during 6-month postoperative follow up. [Conclusion] Submucosal injection of glycerol and fructose saline BT-ESD with a 450 nm blue laser semiconductor treatment machine is a safe and effective method for the treatment of NMIBC.It has advantages of whole enucleation of bladder tumor, clear basal layer, small amount of bleeding, short operation time and few complications.It can be used as a day surgery and is worthy of clinical promotion.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

Objective To compare the clinical efficacy and safety of transurethral 450 nm semiconductor blue laser vaporization enucleation and transurethral resection of bladder tumor(TURBT)in the treatment of non-muscle invasive bladder cancer(NMIBC).Methods The clinical data of 85 NMIBC patients undergoing surgical treatment at Yingsheng Branch of Taian Central Hospital during Dec.2022 and Feb.2024 were retrospectively collected.The patients were divided into the blue laser group(n=40)and TURBT group(n=45).The operation time,intraoperative blood loss,postoperative bladder irrigation time,postoperative catheter indwelling time,postoperative hospital stay,intraoperative complications,wound healing 3 and 6 months after operation,and tumor recurrence 1 year after operation were compared between the two groups.Results Patients in both groups successfully completed the operation without blood transfusion or conversion to open surgery.Compared with the TURBT group,the blue laser group had shorter operation time[(23.68±9.98)min vs.(29.11±14.27)min],less blood loss[(1.43±0.87)g/L vs.(3.27±0.96)g/L],and shorter postoperative bladder irrigation time[0.5(0.5,0.5)d vs.0.5(0.5,1.5)d](P＜0.05).No cases developed obturator nerve reflexes in the blue laser group,but 7 cases in the TURBT group(P＜0.05).Three months after operation,the bladder wounds healed in 24 cases in the blue laser group,but only in 7 cases in the TURBT group(P＜0.01).Conclusion Compared with TURBT,transurethral 450 nm semiconductor blue laser vaporization enucleation for the treatment of NMIBC can shorten the operation time,reduce the amount of bleeding,shorten the postoperative healing time,and cause fewer complications.It is a safe and efficient minimally invasive surgery.

Objective To compare the clinical efficacy and safety of transurethral 450 nm semiconductor blue laser vaporization enucleation and transurethral resection of bladder tumor(TURBT)in the treatment of non-muscle invasive bladder cancer(NMIBC).Methods The clinical data of 85 NMIBC patients undergoing surgical treatment at Yingsheng Branch of Taian Central Hospital during Dec.2022 and Feb.2024 were retrospectively collected.The patients were divided into the blue laser group(n=40)and TURBT group(n=45).The operation time,intraoperative blood loss,postoperative bladder irrigation time,postoperative catheter indwelling time,postoperative hospital stay,intraoperative complications,wound healing 3 and 6 months after operation,and tumor recurrence 1 year after operation were compared between the two groups.Results Patients in both groups successfully completed the operation without blood transfusion or conversion to open surgery.Compared with the TURBT group,the blue laser group had shorter operation time[(23.68±9.98)min vs.(29.11±14.27)min],less blood loss[(1.43±0.87)g/L vs.(3.27±0.96)g/L],and shorter postoperative bladder irrigation time[0.5(0.5,0.5)d vs.0.5(0.5,1.5)d](P＜0.05).No cases developed obturator nerve reflexes in the blue laser group,but 7 cases in the TURBT group(P＜0.05).Three months after operation,the bladder wounds healed in 24 cases in the blue laser group,but only in 7 cases in the TURBT group(P＜0.01).Conclusion Compared with TURBT,transurethral 450 nm semiconductor blue laser vaporization enucleation for the treatment of NMIBC can shorten the operation time,reduce the amount of bleeding,shorten the postoperative healing time,and cause fewer complications.It is a safe and efficient minimally invasive surgery.

Objective:To investigate the efficacy and prognosis of biliary drainage via endoscopic retrograde cholangiopancreatography (ERCP) before steroid therapy in treating autoimmune pancreatitis (AIP) complicated with obstructive jaundice.Methods:A retrospective analysis was performed on clinical data of patients with AIP complicated with obstructive jaundice who received steroid therapy at the First Affiliated Hospital of Naval Medical University from 2010 to 2023. Patients were divided into a drainage group (receiving ERCP biliary drainage before steroid therapy) and a steroid group (receiving only steroid therapy). Short-term efficacy, long-term efficacy, hospitalization costs and postoperative complications of ERCP biliary drainage were compared between the two groups.Results:A total of 69 patients were included, with 32 in the drainage group, aged 62.78±11.21 years, which demonstrated significantly higher costs (34 816.57±11 688.85 yuan VS 16 518.50±6 544.37 yuan, t=7.0, P<0.001), with 25.00% (8/32) experiencing ERCP-related complications, compared with 37 patients in the steroid group, aged 55.41±2.15 years. There was no significant difference in hospitalization duration between the drainage group (10.38±4.56 days) and the steroid group (8.95±4.99 days, t=1.2, P=0.219). After 1 month of treatment, total bilirubin [118.5 (76.2, 309.3) μmol/L VS 48.7 (30.5, 148.4) μmol/L, U=1 728.5, P<0.001] and direct bilirubin [84.5 (47.7, 236.3) μmol/L VS 37.7 (18.3, 105.7) μmol/L, U=1 588.5, P=0.001] levels in the drainage group remained higher than those in the steroid group, while alanine aminotransferase levels were lower [74.0 (46.5,110.5) U/L VS 143.0 (51.0,253.5) U/L, U=769.0, P=0.006]. No significant differences were observed in these biochemical indices between the two groups at 4-month and 12-month follow-ups ( P>0.05). The recurrence rates were 28.1% (9/32) in the drainage group and 21.6% (8/37) in the steroid group, with no significant difference in recurrence rate between groups ( χ2=0.4, P=0.266). Conclusion:ERCP biliary drainage does not significantly improve long-term efficacy or reduce recurrence rates in AIP patients with obstructive jaundice. Instead, it increases the risk of postoperative complications and medical costs. Direct steroid therapy is safe and feasible for confirmed AIP with obstructive jaundice.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

ObjectiveBased on multi-index and multi-method detection， the quality of Rukuaixiao preparations was systematically evaluated from the perspective of characteristic components， and the existing problems were analyzed. MethodsLiquid chromatography-mass spectrometry（LC-MS） for the determination of 16 characteristic components was established to evaluate the quality of 129 batches of Rukuaixiao preparations. High performance liquid chromatography（HPLC） was established to determine the contents of salvianolic acids and tanshinones， investigate the rationality of quality control index of Salviae Miltiorrhizae Radix et Rhizoma in the standard for Rukuaixiao preparations in the 2020 edition of Pharmacopoeia of the People's Republic of China（hereinafter referred to as Chinese Pharmacopoeia） （volume Ⅰ）， and trace the causes of significant difference among different batches. The processing and different extraction methods of Vaccariae Semen were tested， analyzing the impact of formulation changes across different editions of Chinese Pharmacopoeia. The LC-MS was established for determining the changes in the ratio of toosendanin and isotoosendanin after water extraction of Toosendan Fructus. The contents of active components in different parts of Gleditsiae Spina were determined to identify the reason of the low contents of characteristic components in some enterprises. ResultsBased on the comprehensive analysis of the samples from different dosage forms， the contents of characteristic components of Vaccariae Semen and Gleditsiae Spina in tablets from manufacturer B and granules from manufacturer D were significantly higher than those in tablets from manufacturer A， and tablets and capsules from manufacturer C. The contents of tanshinones in some batches of products from manufacturer A were abnormally high， potentially linked to the use of 70% ethanol reflux during extraction of Salviae Miltiorrhizae Radix et Rhizoma. All samples from manufacturer C exhibited abnormally high proportions of salvianic acid A and 3，4-dihydroxybenzaldehyde（salvianolic acid degradation products） to the total seven phenolic acids， indicating a risk of blindly pursuing tanshinol content and neglecting more effective components. The extraction rate of the characteristic components from Vaccariae Semen by decocting with water was obviously higher than that by reflux extraction with 70% ethanol. However， using the stir-fried Vaccariae Semen could reduce the loss of ingredients. The content ratio of toosendanin and isotoosendanin decreased from the crude herb to the prepared medicine when Toosendan Fructus was prepared by water decoction. The reason for the low component content of Gleditsiae Spina may be attributed to manufacturers using excessive non-medicinal parts in their formulations. ConclusionIt is suggested that enterprises should ensure the quality of raw material inputs， especially those without quality-control items in the standard， reduce the use of non-medicinal parts， and prohibit arbitrary alterations to manufacturing methods or processes. It is also recommended that Vaccariae Semen in Rukuaixiao capsules and granules should be changed to the stir-fried processed products. Isotoosendanin should be taken into consideration in the drug supervision when Toosendan Fructus is prepared into medicine by water decoction. Salvianolic acid B should be set as a quality control index for Salviae Miltiorrhizae Radix et Rhizoma when revising the pharmacopoeia standard of Rukuaixiao preparations.

ObjectiveBased on multi-index and multi-method detection， the quality of Rukuaixiao preparations was systematically evaluated from the perspective of characteristic components， and the existing problems were analyzed. MethodsLiquid chromatography-mass spectrometry（LC-MS） for the determination of 16 characteristic components was established to evaluate the quality of 129 batches of Rukuaixiao preparations. High performance liquid chromatography（HPLC） was established to determine the contents of salvianolic acids and tanshinones， investigate the rationality of quality control index of Salviae Miltiorrhizae Radix et Rhizoma in the standard for Rukuaixiao preparations in the 2020 edition of Pharmacopoeia of the People's Republic of China（hereinafter referred to as Chinese Pharmacopoeia） （volume Ⅰ）， and trace the causes of significant difference among different batches. The processing and different extraction methods of Vaccariae Semen were tested， analyzing the impact of formulation changes across different editions of Chinese Pharmacopoeia. The LC-MS was established for determining the changes in the ratio of toosendanin and isotoosendanin after water extraction of Toosendan Fructus. The contents of active components in different parts of Gleditsiae Spina were determined to identify the reason of the low contents of characteristic components in some enterprises. ResultsBased on the comprehensive analysis of the samples from different dosage forms， the contents of characteristic components of Vaccariae Semen and Gleditsiae Spina in tablets from manufacturer B and granules from manufacturer D were significantly higher than those in tablets from manufacturer A， and tablets and capsules from manufacturer C. The contents of tanshinones in some batches of products from manufacturer A were abnormally high， potentially linked to the use of 70% ethanol reflux during extraction of Salviae Miltiorrhizae Radix et Rhizoma. All samples from manufacturer C exhibited abnormally high proportions of salvianic acid A and 3，4-dihydroxybenzaldehyde（salvianolic acid degradation products） to the total seven phenolic acids， indicating a risk of blindly pursuing tanshinol content and neglecting more effective components. The extraction rate of the characteristic components from Vaccariae Semen by decocting with water was obviously higher than that by reflux extraction with 70% ethanol. However， using the stir-fried Vaccariae Semen could reduce the loss of ingredients. The content ratio of toosendanin and isotoosendanin decreased from the crude herb to the prepared medicine when Toosendan Fructus was prepared by water decoction. The reason for the low component content of Gleditsiae Spina may be attributed to manufacturers using excessive non-medicinal parts in their formulations. ConclusionIt is suggested that enterprises should ensure the quality of raw material inputs， especially those without quality-control items in the standard， reduce the use of non-medicinal parts， and prohibit arbitrary alterations to manufacturing methods or processes. It is also recommended that Vaccariae Semen in Rukuaixiao capsules and granules should be changed to the stir-fried processed products. Isotoosendanin should be taken into consideration in the drug supervision when Toosendan Fructus is prepared into medicine by water decoction. Salvianolic acid B should be set as a quality control index for Salviae Miltiorrhizae Radix et Rhizoma when revising the pharmacopoeia standard of Rukuaixiao preparations.