ObjectiveTo investigate the therapeutic effects of the Anemarrhenae Rhizoma water extract （AR） on Alzheimer's disease （AD） model rats and to explore its potential underlying mechanisms. MethodsMale rats were intraperitoneally injected with D-galactose （100 mg·kg^-1） for 42 days， and on day 14， 1 μL of β-amyloid （Aβ_25-35， 2 g·L^-1） solution was injected into the hippocampus. Rats were randomly divided into a model group， low-dose AR （0.6 g·kg^-1）， medium-dose AR （1.2 g·kg^-1）， high-dose AR （2.4 g·kg^-1）， and a positive control group （donepezil， 5 mg·kg^-1）. Healthy rats receiving only a hippocampal injection of 1 μL of sterile saline served as the sham-operated group. From day 21， rats in the treatment groups were administered the corresponding drugs by gavage once daily for 21 consecutive days， while the blank control and model groups received an equal volume of saline. Learning and memory abilities were assessed using the Morris water maze. Brain tissue damage was observed by hematoxylin and eosin （HE） staining， and neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining. Levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10） in brain tissues were measured by enzyme-linked immunosorbent assay （ELISA）. BV2 microglial cells were co-cultured with Aβ_25-35 （40 μmol·L^-1） for 2 h， and cell viability was determined by the CCK-8 assay to screen the optimal concentration of AR-containing serum （S-AR）. Cells were divided into blank control， Aβ_25-35， S-AR， EX527 ［silent information regulator 1 （SIRT1） inhibitor］， and S-AR+EX527 groups. Immunofluorescence staining was used to detect the expression of CD16， CD206， and high-mobility group box 1 （HMGB1）. Western blot analysis was performed to measure the protein expression of CD16， inducible nitric oxide synthase （iNOS）， CD206， arginase （Arg）， and proteins related to the SIRT1/HMGB1/nuclear factor-κB （NF-κB） signaling pathway. ResultsIn vivo experiments showed that， compared with the sham-operated group， the model group exhibited reduced platform crossings and time spent in the target quadrant （P<0.01）， prolonged escape latency， increased hippocampal neuronal apoptosis （P<0.01）， and obvious hippocampal damage. The expression levels of IL-6， TNF-α， IL-10， CD16， and iNOS in brain tissues were significantly elevated （P<0.01）， while CD206 and Arg protein expression showed an increasing trend without statistical significance. Compared with the model group， all AR-treated groups significantly increased platform crossings and target quadrant time （P<0.05， P<0.01）， alleviated hippocampal damage， reduced escape latency and neuronal apoptosis， downregulated the expression of TNF-α， IL-6， CD16， and iNOS （P<0.05， P<0.01）， and upregulated the expression of IL-10， CD206 and Arg （P<0.05， P<0.01）. In vitro experiments demonstrated that， compared with the blank control group， the Aβ_25-35 group showed increased fluorescence intensity of CD206， CD16， and HMGB1， as well as elevated protein expression of iNOS and CD16 （P<0.01）， while CD206 and Arg protein expression exhibited an increasing trend without statistical significance. After S-AR intervention， CD206 fluorescence intensity and the protein expression of Arg and CD206 were significantly increased （P<0.01）， whereas the fluorescence intensity of CD16 and HMGB1 and the protein expression of iNOS and CD16 were significantly decreased （P<0.01）. These effects were reversed by EX527 （P<0.05， P<0.01）. Furthermore， compared with the blank control group， the Aβ_25-35 group showed significantly increased cytoplasmic HMGB1 expression and p-p65/p65 ratio （P<0.01）， along with significantly decreased SIRT1 and nuclear HMGB1 expression （P<0.01）. In contrast， the S-AR group exhibited opposite trends compared with the Aβ_25-35 group， and the regulatory effects of S-AR on these proteins were reversed by EX527 （P<0.01）. ConclusionAR exerts neuroprotective effects in AD model rats by regulating microglial polarization and alleviating neuroinflammation， potentially through modulation of the SIRT1/HMGB1/NF-κB signaling pathway.

Objective:To understand the clinicopathological and molecular genetic characteristics of aggressive renal mucinous tubular and spindle cell carcinoma (MTSCC).Methods:The clinical features, histology, immunophenotype, molecular characteristics and prognosis of 4 cases of metastatic/recurrent renal MTSCC that were submitted to the Peking University Third Hospital (2 cases), Institute of Urology, Peking University (one case) and Zhejiang Provincial People′s Hospital (one case) from 2015 to 2020 were retrospectively reviewed and analyzed.Results:Among the four patients, two were male and two were female. The average age was 58 years, ranging from 28 to 77 years. Three patients underwent radical nephrectomy, while one underwent partial nephrectomy. The tumor size was 2-8 cm (mean, 5.6 cm). There were two cases classified as pT3a, one case as pT1b and one case as pT1a. Histologically, the tumors were mainly composed of tubules and spindle cell cords. For nuclear grade, three cases were G3 and one case was G2. Extracellular mucus was present in all four cases. Sarcomatoid features and tumor necrosis were observed in one and three cases, respectively. Immunohistochemistry showed that PAX8 (4/4), AMACR (4/4), CK7 (4/4), CKpan (3/3), vimentin (3/3) and CK8/18 (2/2) were positive in the tumor cells, but CAⅨ (1/4) or CD10 (2/3) were focally positive or negative. Fluorescence in situ hybridization showed that no trisomy of chromosomes 7 and l7 (2/2). Targeted next generation sequencing were performed in all four cases and showed that 3 cases had mutations in Hippo pathway involving MET (2/4), NF2 (1/4) and NTRK1 (1/4) genes. The other potentially pathogenic mutations involved KDM6A, SETD2 and PALB2. The follow-up period was 13 to 99 months. The time between diagnosis and metastasis/recurrence ranged from 6 to 58 months. Two patients died after lung metastasis occurred, one had multi-organ and multi-site lymph node metastases, and one achieved disease-free survival after resection of metastatic/recurrent foci.Conclusions:Renal MTSCC is a rare and distinct entity. The presence of high nuclear grade and pathological stage, high-grade morphology, lymphovascular invasion, and tumor necrosis suggests potential aggressive behaviors. It is thus recommended to report these histological features and conduct active follow-up and surveillance after surgery. The frequent mutations in MET, NF2 and NTRK1 suggest that dysregulation of Hippo pathway may be related to the development and progression of renal MTSCC.

Objective:To investigate the clinicopathological characteristics, as well as diagnostic and differential diagnostic criteria of perinephric myxoid pseudotumor of fat (PMPF).Methods:Five cases of PMPF were retrospectively collected from the departmental files of Zhejiang Provincial People′s Hospital (4 cases) and Ningbo Clinical Pathology Diagnosis Center (1 cases) from January 2020 to December 2023, the clinical, morphological, and immunohistochemical characteristics were analyzed. Fluorescence in-situ hybridization (FISH) was utilized to detect the amplification status of MDM2 and the rearrangement status of DDIT3.Results:There were 3 male and 2 female patients, with a median age of 57(44,70) years (range 33-77). All 5 lesions were related to other diseases of the abdominal or urinary system: 3 were associated with papillary renal cell carcinoma, xanthogranulomatous pyelonephritis, and aggressive fibromatosis of the abdominal cavity; two had a history of previous abdominal surgery (one with nephrolithotomy and the other with radical prostatectomy). Grossly, all 5 cases presented as mass-forming lesions involving the perirenal and/or renal sinus fat, with a median maximum diameter of 6.5 cm (2.6, 12.0), and range 2.2-16.0 cm. All five cases showed similar microscopic appearances: the lesions were ill-circumscribed and consisted of mature adipocytes and bland stellate and spindled stromal cells setting in a prominent fibromyxoid stroma. Occasionally, vesicular pseudolipoblastic stromal cells with cytoplasmic distension by myxoid secretions were present. All the five lesions lacked cells containing bizarre or hyperchromatic nuclei. Mitosis was not found. An arborizing, thin-walled vasculature and rope-like collagen deposition were present. A variably intense mixed inflammatory cell infiltrate was observed in all 5 cases, with lymphoid follicle formation in 3 cases. By immunohistochemistry, the adipocytes expressed S-100 protein while the spindle cells did not in all 5 cases. The spindled cells expressed CD34, p16 and smooth muscle actin in 3/5, 2/5, and 1/5 cases, respectively, with the stains being focally in all the cases; the Ki-67 proliferation index was<2%. The other detected markers were all negative, including CDK4, MDM2, desmin, HMB45, Melan A, NY-ESO-1, ALK, and MUC4. The IgG-positive plasma cells were all less than 5 per high-power field, and IgG4-positive cells were absent in all lesions. The FISH analysis showed negative for MDM2 gene amplification or DDIT3 gene rearrangement. None of the 5 patients showed disease recurrence or progression related to PMPF during a follow-up from 15 to 54 months (mean: 37 months).Conclusions:PMPF is a rare and novel non-neoplastic lesion that is often associated with or secondary to other abdominal or urinary system diseases. It can mimic well-differentiated liposarcoma on both imaging and morphology. Careful histological observation combined with immunohistochemical and molecular genetic analyses can aid in its diagnosis and differential diagnosis.

Objective:To understand the clinicopathological and molecular genetic characteristics of aggressive renal mucinous tubular and spindle cell carcinoma (MTSCC).Methods:The clinical features, histology, immunophenotype, molecular characteristics and prognosis of 4 cases of metastatic/recurrent renal MTSCC that were submitted to the Peking University Third Hospital (2 cases), Institute of Urology, Peking University (one case) and Zhejiang Provincial People′s Hospital (one case) from 2015 to 2020 were retrospectively reviewed and analyzed.Results:Among the four patients, two were male and two were female. The average age was 58 years, ranging from 28 to 77 years. Three patients underwent radical nephrectomy, while one underwent partial nephrectomy. The tumor size was 2-8 cm (mean, 5.6 cm). There were two cases classified as pT3a, one case as pT1b and one case as pT1a. Histologically, the tumors were mainly composed of tubules and spindle cell cords. For nuclear grade, three cases were G3 and one case was G2. Extracellular mucus was present in all four cases. Sarcomatoid features and tumor necrosis were observed in one and three cases, respectively. Immunohistochemistry showed that PAX8 (4/4), AMACR (4/4), CK7 (4/4), CKpan (3/3), vimentin (3/3) and CK8/18 (2/2) were positive in the tumor cells, but CAⅨ (1/4) or CD10 (2/3) were focally positive or negative. Fluorescence in situ hybridization showed that no trisomy of chromosomes 7 and l7 (2/2). Targeted next generation sequencing were performed in all four cases and showed that 3 cases had mutations in Hippo pathway involving MET (2/4), NF2 (1/4) and NTRK1 (1/4) genes. The other potentially pathogenic mutations involved KDM6A, SETD2 and PALB2. The follow-up period was 13 to 99 months. The time between diagnosis and metastasis/recurrence ranged from 6 to 58 months. Two patients died after lung metastasis occurred, one had multi-organ and multi-site lymph node metastases, and one achieved disease-free survival after resection of metastatic/recurrent foci.Conclusions:Renal MTSCC is a rare and distinct entity. The presence of high nuclear grade and pathological stage, high-grade morphology, lymphovascular invasion, and tumor necrosis suggests potential aggressive behaviors. It is thus recommended to report these histological features and conduct active follow-up and surveillance after surgery. The frequent mutations in MET, NF2 and NTRK1 suggest that dysregulation of Hippo pathway may be related to the development and progression of renal MTSCC.

Objective:To investigate the clinicopathological characteristics, as well as diagnostic and differential diagnostic criteria of perinephric myxoid pseudotumor of fat (PMPF).Methods:Five cases of PMPF were retrospectively collected from the departmental files of Zhejiang Provincial People′s Hospital (4 cases) and Ningbo Clinical Pathology Diagnosis Center (1 cases) from January 2020 to December 2023, the clinical, morphological, and immunohistochemical characteristics were analyzed. Fluorescence in-situ hybridization (FISH) was utilized to detect the amplification status of MDM2 and the rearrangement status of DDIT3.Results:There were 3 male and 2 female patients, with a median age of 57(44,70) years (range 33-77). All 5 lesions were related to other diseases of the abdominal or urinary system: 3 were associated with papillary renal cell carcinoma, xanthogranulomatous pyelonephritis, and aggressive fibromatosis of the abdominal cavity; two had a history of previous abdominal surgery (one with nephrolithotomy and the other with radical prostatectomy). Grossly, all 5 cases presented as mass-forming lesions involving the perirenal and/or renal sinus fat, with a median maximum diameter of 6.5 cm (2.6, 12.0), and range 2.2-16.0 cm. All five cases showed similar microscopic appearances: the lesions were ill-circumscribed and consisted of mature adipocytes and bland stellate and spindled stromal cells setting in a prominent fibromyxoid stroma. Occasionally, vesicular pseudolipoblastic stromal cells with cytoplasmic distension by myxoid secretions were present. All the five lesions lacked cells containing bizarre or hyperchromatic nuclei. Mitosis was not found. An arborizing, thin-walled vasculature and rope-like collagen deposition were present. A variably intense mixed inflammatory cell infiltrate was observed in all 5 cases, with lymphoid follicle formation in 3 cases. By immunohistochemistry, the adipocytes expressed S-100 protein while the spindle cells did not in all 5 cases. The spindled cells expressed CD34, p16 and smooth muscle actin in 3/5, 2/5, and 1/5 cases, respectively, with the stains being focally in all the cases; the Ki-67 proliferation index was<2%. The other detected markers were all negative, including CDK4, MDM2, desmin, HMB45, Melan A, NY-ESO-1, ALK, and MUC4. The IgG-positive plasma cells were all less than 5 per high-power field, and IgG4-positive cells were absent in all lesions. The FISH analysis showed negative for MDM2 gene amplification or DDIT3 gene rearrangement. None of the 5 patients showed disease recurrence or progression related to PMPF during a follow-up from 15 to 54 months (mean: 37 months).Conclusions:PMPF is a rare and novel non-neoplastic lesion that is often associated with or secondary to other abdominal or urinary system diseases. It can mimic well-differentiated liposarcoma on both imaging and morphology. Careful histological observation combined with immunohistochemical and molecular genetic analyses can aid in its diagnosis and differential diagnosis.

OBJECTIVE：To observe the effects of Compound danshen drip ping pills on the prevention of contrast-induced nephropathy（CIN）after percutaneous coronary intervention （PCI）and its influence on clinical prognosis. METHODS ：From Jan. to Jun. 2020，240 patients with coronary heart disease receiving PCI in Tianjin Chest Hospital were randomly divided into control group（120 cases）and Danshen dripping pills group （120 cases）according to random number table. The patients in both groups were injected with Lippaclitanol injection 1-5 mL slowly through radial or femoral artery sheath ，and intravenous hydration was performed before and after PCI ；Danshen dripping pills group was additionally given Compound danshen dripping pills 270 mg orally for a long term ，three times a day ，three days before and after PCI ，on the basis of the control group. The levels of renal function indexes [serum creatinine （Scr），blood urea nitrogen （BUN），cystatin C （Cys-C），creatinine clearance rate （Ccr）]， inflammatory reaction indexes [high sensitivity C-reactive protein （hs-CRP）， interleukin-6 （IL-6）] and oxidative stress index [malondialdehyde （MDA）] were observed in 2 groups before and 72 hours after PCI. The occurrence of CIN in 2 groups was recorded 3 days after PCI therapy ；the occurrence of major cardiovascular adverse events was also observed during 1-year follow-up period. RESULTS ：Before treatment ，there was no significant difference in serum renal function indexes ，inflammatory reaction indexes and oxidative stress index between 2 groups（P＞0.05）. Seventy-two hours after PCI ，serum levels of Scr ，BUN， Cys-C，hs-CRP，IL-6 and MDA were increased significantly in 2 groups than before treatment ，while the Ccr were decreased significantly；those indexes of Danshen dripping pills group were significantly better than those of control group （P＜ 0.05）. The incidence of CIN in Danshen dripping pills group was 4.2％ after treatment ， and total incidence of major cardiovascular adverse events was 13.3％ during follow-up period，which were sign ificantly lower than 13.3％ and 27.5％ of control group （P＜0.05）. CONCLUSIONS ：Compound danshen dripping pills may have a certain effect on the prevention of CIN in coronary heart disease patients after PCI ，and can reduce the incidence of major cardiovascular adverse events.