Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective To investigate the effect of indigo on inflammatory factors and the aryl hydrocarbon receptor(AhR)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in lipopolysaccharide(LPS)-induced keratinocytes(HaCaT cells).Methods An LPS-induced HaCaT cell model was established,and experimental groups were set as follows:blank group,model group,indigo group,AhR agonist(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)group,AhR inhibitor(CH-223191)group,and indigo+AhR inhibitor group.The Cell Counting Kit-8(CCK-8)assay was used to detect the effects of different concentrations of indigo,TCDD,and CH-223191 on HaCaT cell viability after 24 hours of intervention.Quantitative real-time PCR(qPCR)was employed to measure the mRNA expression levels of interleukin-1β(IL-1β),nuclear factor kappa B(NF-κB),tumor necrosis factor-α(TNF-α),AhR,cytochrome P450 family 1 subfamily A member 1(CYP1A1),NLRP3,Caspase-1,and apoptosis-associated speck-like protein(ASC)in each group.Western Blot analysis was used to assess changes in the cellular localization of AhR protein expression.Results(1)The IC50 of indigo intervention in HaCaT cells was 118.7 μmol·L-1.Treatment with different concentrations of CH-223191 and TCDD for 24 hours had no significant effect on HaCaT cell viability.(2)Compared with the model group,the indigo group showed decreased mRNA expression levels of IL-1β,NF-κB,NLRP3,and Caspase-1(P＜0.05 or P＜0.000 1),while the mRNA expression levels of AhR and CYP1A1 were significantly increased(P＜0.05 or P＜0.000 1).(3)Compared with the blank group,the indigo group reduced cytoplasmic AhR protein expression and increased nuclear AhR protein expression(P＜0.001 or P＜0.000 1).(4)Compared with the model group,both the indigo group and the AhR agonist group significantly increased AhR mRNA expression levels(P＜0.05),while the AhR inhibitor group decreased AhR and CYP1A1 mRNA expression levels(P＜0.05)and increased IL-1β and NLRP3 mRNA expression levels(P＜0.05).(5)Compared with the AhR inhibitor group,the indigo+AhR inhibitor group showed increased mRNA expression levels of AhR and CYP1A1(P＜0.05)and decreased mRNA expression levels of NLRP3,Caspase-1,and IL-1β(P＜0.05).Conclusion Indigo reduces inflammatory factors in LPS-induced HaCaT cells and participates in inhibiting the occurrence and development of psoriasis by activating AhR to negatively regulate the NLRP3 inflammasome.

Objective:To analyze the clinical efficacy of laparoscopic common bile duct exploration and stone removal via the cystic duct with a flexible ureteroscope.Methods:The clinical data of 96 patients with cholecystolithiasis and choledocholithiasis who were admitted to the Department of Hepatobiliary Surgery, the Third Hospital of Nanchang from September 2021 to November 2024 were retrospectively analyzed. There were 49 male and 47 female patients, aged (59.2±13.9) years. The 96 patients were randomly divided into two groups according to the surgical methods: the flexible ureteroscope group ( n=48) and the choledochotomy group ( n=48), patients who underwent laparoscopic cholecystectomy plus flexible ureteroscope for common bile duct exploration and stone removal via the cystic duct were included in the flexible ureteroscope group; patients who underwent laparoscopic cholecystectomy plus choledocholithotomy and T-tube drainage placement were included in the choledochotomy group. Clinical data including operation time, intraoperative blood loss, postoperative intestinal function recovery time, abdominal drainage tube removal time, postoperative hospital stay and postoperative complications were compared between the two groups. Results:Compared with the choledochotomy group, the operation time [150 (120, 176) min vs. 197 (165, 240) min], intraoperative blood loss [20 (10, 30) ml vs. 30 (20, 50) ml], postoperative intestinal function recovery time [2 (1, 2) d vs. 3 (2, 4) d], abdominal drainage tube removal time [6 (4, 7) d vs. 7 (6, 8) d], and postoperative hospital stay [8 (6, 9) d vs. 16 (13, 17) d] in the flexible ureteroscope group were all reduced, and the differences were statistically significant (all P<0.05). The incidence of postoperative complications in the choledochotomy group was 10.4% (5/48), compared with 2.1% (1/48) in the flexible ureteroscope group. There was no statistically significant difference ( χ2=1.60, P=0.206). Conclusion:Compared with laparoscopic choledocholithotomy plus T-tube drainage, laparoscopic common bile duct exploration and stone removal via the cystic duct with a flexible ureteroscope can shorten the hospital stay of patients with choledocholithiasis, offering a minimally invasive, safe and effective treatment method.

Objective To study the efficacy and safety of flexible ureteroscopy holmium laser lithotripsy(FURS)in the treatment of urinary tract stones of different sizes and positions.Methods A retrospective analysis was conducted on the clinical data of 121 patients with upper urinary tract stones from January 2021 to December 2023.According to the size of the stones,they were divided into the diameter ≤20 mm group(n=98)and the 20 mm＜diameter ≤40 mm group(n=23).According to the location of the stones,19 cases were divided into the renal pelvis stone group and 102 cases were non renal pelvis stones.The surgical related indicators and incidence of complications were compared between the groups.Result The operation time of the group with diameter ≤20 mm and the group with diameter 20 mm＜diameter ≤40 mm was(44.13±12.6)minutes and(57.52±20.98)minutes,respectively.The hospitalization periods were(4.55±1.54)days and(5.74±2.00)days,respectively.There were statistically significant differences between the two groups(P＜0.05).The stone clearance rates in the group with diameter ≤ 20 mum and the group with 20 mum＜diameter ≤ 40 mum were 84.69％and 78.26％,respectively.There was no statistically significant difference between the two groups(P＞0.05).The operation time of the subcalyx kidney stone group and the non-subcalyx kidney stone group was(44.05±11.08)minutes and(47.17±16.19)minutes respectively,the hospital stay was(4.74±1.52)days and(4.78±1.73)days respectively,and the ESWL selection rates after the operation were 5.26％and 10.78％respectively.The stone recurrence rates were 15.79％and 4.90％respectively,and there was no statistically significant difference between the two groups(P＞0.05).The stone clearance rates in the subcalyx kidney stone group and the non-subcalyx kidney stone group were 63.16％and 87.25％,respectively.There was a statistically significant difference between the two groups(P＜0.05).There was no statistically significant difference in the incidences of urosepsis,fever,low back pain,hematuria and total complications between the 20 mm＜diameter ≤40 mm group and the diameter ≤20 mm group(P＞0.05).There was no statistically significant difference in the incidences of urosepsis,fever,low back pain,hematuria and total complications between the non-inferior calyx stone group and the inferior calyx stone group(P＞0.05).Conclusion FURS treatment for upper urinary tract stones with a diameter of≤20 mm has shorter surgical and hospitalization times compared to patients with a diameter of≤40 mm.ESWL and lower stone recurrence rates are also preferred after surgery.FURS treatment for non lower renal calyx stones has a higher stone clearance rate compared to lower renal calyx stones.The safety of FURS treatment for upper urinary tract stones of different sizes and positions is equivalent.

Objective To investigate and observe the morphology of subcutaneous induced membrane and osteogenic factor expres-sion of the novel material calcium hydroxide-bone cement.Methods 15 4-week-old Specific Pathogen Free(SPF)female Kunming mice were randomly divided into three groups(n=5):experimental group,control group and blank group.A cut running deep under the skin was made on the back side,calcium hydroxide-bone cement was placed subcutaneously in the experimental group,the Polymethyl Methacrylate(PMMA)was placed subcutaneously in the control group,the blank group only with operation.After 6 weeks,the subcuta-neous tissue surrounded the material was taken from each group to be observed the pathological structure,calculated the collagen volume fraction(CVF)and detected the positive expression and relative expression of osteogenic factors such as bone morphogenetic protein-2(BMP-2),transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF)in the subcutaneous tissues.Results Comparing with the pathological sections of the blank group,there were induced membrane structure rich in collagenous fiber,microvessel and cell in subcutaneous tissue of the control and experimental groups.Comparing with control group,there were decrease of inflammatory cells,collagen content,microvessels,and disorder of collagenous fiber in experimental group.Comparing the CVF,average optical density(AOD)of osteogenic factors and grey scale value of protein bands in each group,the blank group,experimental group and control group increased sequentially,and there was a significant difference between each group(P＜0.05).Conclusion The new mate-rial,calcium hydroxide-bone cement,can form an induced membrane structure subcutaneously,but the 6-week induced membrane was not as good as the PMMA induced membrane during the same period in terms of morphology and osteogenic factor levels.

Objective To study the efficacy and safety of flexible ureteroscopy holmium laser lithotripsy(FURS)in the treatment of urinary tract stones of different sizes and positions.Methods A retrospective analysis was conducted on the clinical data of 121 patients with upper urinary tract stones from January 2021 to December 2023.According to the size of the stones,they were divided into the diameter ≤20 mm group(n=98)and the 20 mm＜diameter ≤40 mm group(n=23).According to the location of the stones,19 cases were divided into the renal pelvis stone group and 102 cases were non renal pelvis stones.The surgical related indicators and incidence of complications were compared between the groups.Result The operation time of the group with diameter ≤20 mm and the group with diameter 20 mm＜diameter ≤40 mm was(44.13±12.6)minutes and(57.52±20.98)minutes,respectively.The hospitalization periods were(4.55±1.54)days and(5.74±2.00)days,respectively.There were statistically significant differences between the two groups(P＜0.05).The stone clearance rates in the group with diameter ≤ 20 mum and the group with 20 mum＜diameter ≤ 40 mum were 84.69％and 78.26％,respectively.There was no statistically significant difference between the two groups(P＞0.05).The operation time of the subcalyx kidney stone group and the non-subcalyx kidney stone group was(44.05±11.08)minutes and(47.17±16.19)minutes respectively,the hospital stay was(4.74±1.52)days and(4.78±1.73)days respectively,and the ESWL selection rates after the operation were 5.26％and 10.78％respectively.The stone recurrence rates were 15.79％and 4.90％respectively,and there was no statistically significant difference between the two groups(P＞0.05).The stone clearance rates in the subcalyx kidney stone group and the non-subcalyx kidney stone group were 63.16％and 87.25％,respectively.There was a statistically significant difference between the two groups(P＜0.05).There was no statistically significant difference in the incidences of urosepsis,fever,low back pain,hematuria and total complications between the 20 mm＜diameter ≤40 mm group and the diameter ≤20 mm group(P＞0.05).There was no statistically significant difference in the incidences of urosepsis,fever,low back pain,hematuria and total complications between the non-inferior calyx stone group and the inferior calyx stone group(P＞0.05).Conclusion FURS treatment for upper urinary tract stones with a diameter of≤20 mm has shorter surgical and hospitalization times compared to patients with a diameter of≤40 mm.ESWL and lower stone recurrence rates are also preferred after surgery.FURS treatment for non lower renal calyx stones has a higher stone clearance rate compared to lower renal calyx stones.The safety of FURS treatment for upper urinary tract stones of different sizes and positions is equivalent.

Objective To investigate and observe the morphology of subcutaneous induced membrane and osteogenic factor expres-sion of the novel material calcium hydroxide-bone cement.Methods 15 4-week-old Specific Pathogen Free(SPF)female Kunming mice were randomly divided into three groups(n=5):experimental group,control group and blank group.A cut running deep under the skin was made on the back side,calcium hydroxide-bone cement was placed subcutaneously in the experimental group,the Polymethyl Methacrylate(PMMA)was placed subcutaneously in the control group,the blank group only with operation.After 6 weeks,the subcuta-neous tissue surrounded the material was taken from each group to be observed the pathological structure,calculated the collagen volume fraction(CVF)and detected the positive expression and relative expression of osteogenic factors such as bone morphogenetic protein-2(BMP-2),transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF)in the subcutaneous tissues.Results Comparing with the pathological sections of the blank group,there were induced membrane structure rich in collagenous fiber,microvessel and cell in subcutaneous tissue of the control and experimental groups.Comparing with control group,there were decrease of inflammatory cells,collagen content,microvessels,and disorder of collagenous fiber in experimental group.Comparing the CVF,average optical density(AOD)of osteogenic factors and grey scale value of protein bands in each group,the blank group,experimental group and control group increased sequentially,and there was a significant difference between each group(P＜0.05).Conclusion The new mate-rial,calcium hydroxide-bone cement,can form an induced membrane structure subcutaneously,but the 6-week induced membrane was not as good as the PMMA induced membrane during the same period in terms of morphology and osteogenic factor levels.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective:To analyze the clinical efficacy of laparoscopic common bile duct exploration and stone removal via the cystic duct with a flexible ureteroscope.Methods:The clinical data of 96 patients with cholecystolithiasis and choledocholithiasis who were admitted to the Department of Hepatobiliary Surgery, the Third Hospital of Nanchang from September 2021 to November 2024 were retrospectively analyzed. There were 49 male and 47 female patients, aged (59.2±13.9) years. The 96 patients were randomly divided into two groups according to the surgical methods: the flexible ureteroscope group ( n=48) and the choledochotomy group ( n=48), patients who underwent laparoscopic cholecystectomy plus flexible ureteroscope for common bile duct exploration and stone removal via the cystic duct were included in the flexible ureteroscope group; patients who underwent laparoscopic cholecystectomy plus choledocholithotomy and T-tube drainage placement were included in the choledochotomy group. Clinical data including operation time, intraoperative blood loss, postoperative intestinal function recovery time, abdominal drainage tube removal time, postoperative hospital stay and postoperative complications were compared between the two groups. Results:Compared with the choledochotomy group, the operation time [150 (120, 176) min vs. 197 (165, 240) min], intraoperative blood loss [20 (10, 30) ml vs. 30 (20, 50) ml], postoperative intestinal function recovery time [2 (1, 2) d vs. 3 (2, 4) d], abdominal drainage tube removal time [6 (4, 7) d vs. 7 (6, 8) d], and postoperative hospital stay [8 (6, 9) d vs. 16 (13, 17) d] in the flexible ureteroscope group were all reduced, and the differences were statistically significant (all P<0.05). The incidence of postoperative complications in the choledochotomy group was 10.4% (5/48), compared with 2.1% (1/48) in the flexible ureteroscope group. There was no statistically significant difference ( χ2=1.60, P=0.206). Conclusion:Compared with laparoscopic choledocholithotomy plus T-tube drainage, laparoscopic common bile duct exploration and stone removal via the cystic duct with a flexible ureteroscope can shorten the hospital stay of patients with choledocholithiasis, offering a minimally invasive, safe and effective treatment method.

Objective:To explore the clinical characteristics and risk factors of pediatric kidney transplantation (KT).Methods:From January 1, 2010 to September 30, 2022, retrospective analysis was performed for the relevant clinical data of 81 pediatric recipients of primary KT at Organ Transplant Center of Shanghai Changzheng Hospital. The occurrences of acute rejection (AR) ,delayed graft function (DGF), infection, myelosuppression, tumor and other complications were observed within 1 year post-KT. They were grouped according to whether or not AR/DGF occurred. Univariate analysis speculated the effect of AR and DGF on renal function at 1 year after transplantation. Binary Logistic regression was employed for examining the risk factors related to AR/DGF.Results:During follow-ups, transplanted kidney was removed due to an embolization of renal vessels and dialysis resumed (n= 5). One child had failed graft due to the recurrence of original disease and dialysis resumed. The remaining 75 children had an excellent recovery of graft function. At the end of follow-ups, survival for transplant recipients and transplanted kidneys was 100% (81/81 ) and 92.6% (75/81) respectively. 23 patients (28.4%) developed DGF, including 20 child recipients of C-I donors. Among DGF recipients, 21 (91.3%) were immune induced with anti-CD25 humanized monoclonal antibody and 2 (8.7 %) with porcine antihuman lymphocyte immunoglobulin (pALG). Within the first year post-KT, 13 patients (16.1%) developed AR, including 11 child recipients of C-I donors. Induction was made with anti-CD25 humanized monoclonal antibody (n=8), pALG (n=4) and anti-human T lymphocyte rabbit immunoglobulin (n=1). And 12 cases were reversed with MP (methylprednisolone) shock therapy while another ineffective case was rescued by an intravenous infusion of rATG (rabbit anti-human thymocyte immunoglobulin). During postoperative follow-ups, 14 (17.3 %) KT recipients had an onset of pulmonary infection (n=7), upper respiratory tract infection (n=3), urinary tract infection (n=5), gastrointestinal infection (n=2) and abdominal cavity infection (n=1). The causative pathogens were bacteria (n=14) and viruses (n=4). Among 7 cases (8.6%) of myelosuppression, there were leukopenia (n=6) and thrombocytopenia (n=1 ). During 1-year follow-ups, no malignancy occurred. At the last follow-up, blood creatinine was (72.79±21.07) μmol/L in non-AR/DGF recipients. For AR/DGF recipients, blood creatinine levels were (68.83±10.78) and (74.20±18.70) μmol/L. There was no significant inter-group difference ( F=0.14, P=0.87). In groups with and without DGF, the incidence of bone marrow suppression in the children with DGF was significantly higher (21. 74 %) than that in the untreated group (3.45%), with a statistically significant difference ( P=0.02). However, there was no statistically significant difference in the age, sex, donor source, infection, and types of immune-induced drugs in AR, DGF occurrence and no occurrence group. logistic Regression analysis showed that immunoinduction therapy with lymphocyte inhibitor ( OR=0.074, 95 %CI: 0.009-0.0643, P=0.018) and bone marrow suppression ( OR=0.045, 95%CI: 0.004-0.515, P=0.013) were risk factors for DGF. Conclusion:KT in children may obtain decent outcomes. Immunoinduction therapy with lymphocyte inhibitors and occurrence of myelosuppression are risk factors for postoperative DGF. The occurrence of AR/DGF in early postoperative period does not affect the level of kidney function in children at 1 year post-KT. It is recommended to closely follow up and accumulate experiences for optimizing long-term outcomes.