AIM:To explore the effect of sinomenine hydrochloride(SH)on microcirculation and renal func-tion in type 2 diabetic db/db mice with a focus on the diacylglycerol(DAG)/protein kinase C(PKC)signaling pathway.METHODS:Eighteen 6-week-old male db/db mice were randomly divided into three groups:model group(saline),LY group(administered with 1 mg·kg-1·d-1 LY333531),and SH group(administered with 124.8 mg·kg-1·d-1 SH).Addi-tionally,6 age-matched db/m mice comprised the control group(saline).Daily intragastric administration lasted 6 weeks.Body mass,fasting blood glucose(FBG),urinary microalbumin(mALB),urinary creatinine(UCr)and urinary β2-micro-globulin(β2-MG)were measured in each group.The serum levels of endothelin-1(ET-1),endothelial nitric oxide syn-thase(eNOS),collagen type Ⅳ(Col Ⅳ)and laminin(LN),and the levels of DAG and PKC in renal tissues were ana-lyzed by enzyme-linked immunosorbent assay(ELISA).The morphological changes of renal tissues were assessed using HE and PAS staining,and kidney ultrastructure was examined via transmission electron microscopy.Immunohistochemis-try and Western blot were used to detect PKC and p-PKC levels in renal tissues.RESULTS:Compared with model group,the mice in both LY and SH groups showed decreased body mass(P＜0.05),with significantly reduced FBG level in LY group(P＜0.01).In addition,the urinary mALB and β2-MG levels were markedly decreased(P＜0.01),while UCr level was significantly increased(P＜0.01).Serum ET-1,Col Ⅳ and LN levels were significantly lower(P＜0.01),whereas eNOS level was notably higher(P＜0.01).Renal tissue DAG and PKC levels,as well as p-PKC expression were significantly reduced(P＜0.01).Improvements in renal tissue pathology and ultrastructure were observed.CONCLU-SION:Sinomenine hydrochloride improves microcirculation in diabetic db/db mice by modulating DAG/PKC signaling pathway,thus exerting protective effect on the kidney.

AIM:To explore the effect of sinomenine hydrochloride(SH)on microcirculation and renal func-tion in type 2 diabetic db/db mice with a focus on the diacylglycerol(DAG)/protein kinase C(PKC)signaling pathway.METHODS:Eighteen 6-week-old male db/db mice were randomly divided into three groups:model group(saline),LY group(administered with 1 mg·kg-1·d-1 LY333531),and SH group(administered with 124.8 mg·kg-1·d-1 SH).Addi-tionally,6 age-matched db/m mice comprised the control group(saline).Daily intragastric administration lasted 6 weeks.Body mass,fasting blood glucose(FBG),urinary microalbumin(mALB),urinary creatinine(UCr)and urinary β2-micro-globulin(β2-MG)were measured in each group.The serum levels of endothelin-1(ET-1),endothelial nitric oxide syn-thase(eNOS),collagen type Ⅳ(Col Ⅳ)and laminin(LN),and the levels of DAG and PKC in renal tissues were ana-lyzed by enzyme-linked immunosorbent assay(ELISA).The morphological changes of renal tissues were assessed using HE and PAS staining,and kidney ultrastructure was examined via transmission electron microscopy.Immunohistochemis-try and Western blot were used to detect PKC and p-PKC levels in renal tissues.RESULTS:Compared with model group,the mice in both LY and SH groups showed decreased body mass(P＜0.05),with significantly reduced FBG level in LY group(P＜0.01).In addition,the urinary mALB and β2-MG levels were markedly decreased(P＜0.01),while UCr level was significantly increased(P＜0.01).Serum ET-1,Col Ⅳ and LN levels were significantly lower(P＜0.01),whereas eNOS level was notably higher(P＜0.01).Renal tissue DAG and PKC levels,as well as p-PKC expression were significantly reduced(P＜0.01).Improvements in renal tissue pathology and ultrastructure were observed.CONCLU-SION:Sinomenine hydrochloride improves microcirculation in diabetic db/db mice by modulating DAG/PKC signaling pathway,thus exerting protective effect on the kidney.

Objective:To study the clinicopathological features of Sjogren′s syndrome (SS) with liver injury and to improve the understanding of this disease.Methods:Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson′s trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted .Results:The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group ( P=0.006) and NALFD group ( P=0.011) were significantly higher than those in other groups ( P<0.05). Conclusions:The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.

Objective:To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests.Methods:Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope ? hybridization and electron microscopy. Results:All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri′s bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope ? hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions:The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

AIM:This study aimed to investigate the effects of sinomenine hydrochloride(SIN)on the ultra-structure of renal tissue and the expression of interferon gene-stimulating factor in db/db mice.METHODS:Sixteen 12-week-old male db/db mice were randomly divided into two groups:a model group and a sinomenine hydrochloride(SIN)group,each consisting of 8 mice.An additional 8 wild-type(WT)mice served as the normal control group.The sinome-nine hydrochloride group was administered the treatment for 8 weeks,followed by a 20-week observation period,while the normal and model groups received an equal volume of saline via gavage.Weekly measurements were taken for body weight and fasting blood glucose.Serum creatinine(SCr)and blood urea nitrogen(BUN)levels were assessed,and 24-hour uri-nary microalbumin(ALB)levels,as well as serum inflammatory cytokines interleukin-1β(IL-1β),IL-6 and tumor necro-sis factor-α(TNF-α),were determined using ELISA.Pathological changes in renal tissue were evaluated through hema-toxylin-eosin(HE)staining,while ultrastructural alterations were examined using transmission electron microscopy.Im-munohistochemistry and Western blotting were employed to assess STING protein expression in renal tissue,and STING mRNA expression was quantified via RT-qPCR.RESULTS:Compared to the normal group,the model group exhibited significant increases in BUN,ALB,and SCr levels(P<0.01),alongside elevated inflammatory markers IL-1β,IL-6,and TNF-α(P<0.01).Notable pathological changes included leukocyte wall thickening in capillaries,inflammatory cell infiltration,increased mesangial matrix,disorganized and linear alignment of podocytes,and thickening of the basement membrane.Moreover,STING protein and mRNA expression levels were significantly elevated(P<0.01).In contrast,the sinomenine hydrochloride group demonstrated significantly reduced levels of renal function markers(BUN,ALB and SCr)compared to the model group(P<0.01),as well as decreased concentrations of inflammatory factors IL-1β,IL-6,and TNF-α(P<0.01).Improvements in renal histopathology included decreased leukocyte wall thickening,reduced inflam-matory cell presence,diminished mesangial matrix,and a significant reduction in foot process fusion,alongside thinner basement membranes.Both STING protein and mRNA expression levels were also significantly lower(P<0.01).CON-CLUSION:Sinomenine hydrochloride effectively mitigates renal tissue injury,improves ultrastructural alterations,and inhibits inflammatory responses in db/db mice.Its mechanism of action appears closely linked to the downregulation of STING protein and mRNA expression.

Objective:To explore the value in differentiating Borrmann Ⅳ type gastric cancer (BT4-GC) from gastric diffuse large B-cell lymphoma (DLBCL) using a nomogram based on CT texture analysis (CTTA) and morphological characteristics.Methods:From June 2011 to December 2020, a total of 60 patients with BT4-GC and 24 patients with DLBCL were retrospectively collected in Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University. Morphological characteristics were evaluated, including major location, long axis range, circumferential range, mucosal line status, and perigastric enlarged lymph nodes. CTTA parameters were calculated using venous CT images with a manual region of interest. The morphological characteristics and CTTA parameters between BT4-GC and DLBCL were compared by χ 2 test, Fisher exact test or Mann-Whitney U test. The multivariate binary logistic regression analysis was used to filter factors into the diagnostic model and construct a nomogram. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of CTTA parameters and the diagnostic model in differentiating BT4-GC from DLBCL. Results:For morphological characteristics, mucosal line status showed a significant difference between BT4-GC and DLBCL (χ 2=12.99, P<0.001). For CTTA parameters, 16 parameters showed significant differences between BT4-GC and DLBCL (all P<0.05). The area under the ROC curve (AUC) of 16 CTTA parameters in differentiating BT4-GC from DLBCL was 0.662-0.833. Percentile 90 showed the highest AUC of 0.833 (95%CI 0.736-0.906). The mucosal line status (OR 4.82, 95%CI 1.21-19.25, P=0.026) and percentile 90 (OR 1.09, 95%CI 1.04-1.15, P=0.001) were brought into the diagnostic model and constructed a nomogram. The AUC of the model in differentiating BT4-GC from DLBCL was 0.898 (95%CI 0.813-0.953), sensitivity was 0.833, and specificity was 0.817. Conclusions:The nomogram based on CTTA percentile 90 and morphological characteristics mucosal line status can effectively distinguish BT4-GC from DLBCL and shows high diagnostic efficacy.

Objective:To investigate the intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) among patients with type 2 diabetes mellitus (T2DM).Methods:A diagnostic test. In this prospective study, patients with T2DM who underwent both IVIM-DWI and renal biopsy at the First Medical Center of Chinese PLA General Hospital between October 2017 and September 2021 were consecutively enrolled. IVIM-DWI parameters including perfusion fraction (f), pure diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were measured in the renal cortex, medulla, and parenchyma. Patients were divided into the DN group and NDRD group based on the renal biopsy results. IVIM-DWI parameters, clinical information, and diabetes-related biochemical indicators between the two groups were compared using Student′s t-test or Mann-Whitney U test. The correlation of IVIM-DWI parameters with diabetic nephropathy histological scores were analyzed using Spearman′s correlation analyzes. The diagnostic efficiency of IVIM-DWI parameters for distinguishing between DN and NDRD were assessed using the receiver operating characteristic (ROC) curves. Results:A total of 27 DN patients and 23 NDRD patients were included in this study. The DN group comprised 19 male and 8 female patients, with an average age of 52±9 years. The NDRD group comprised 16 male and 7 female patients, with an average age of 49±10 years. The DN group had a higher D* value in the renal cortex and a lower f value in the renal medulla than the NDRD group (9.84×10 -3 mm 2/s vs. 7.35×10 -3 mm 2/s, Z=-3.65; 41.01% vs. 46.74%, Z=-2.29; all P<0.05). The renal medulla D* value was negatively correlated with DN grades, interstitial lesion score, and interstitial fibrosis and tubular atrophy (IFTA) score ( r=-0.571, -0.409, -0.409; all P<0.05) while the renal cortex f value was positively correlated with vascular sclerosis score ( r=0.413, P=0.032). The renal cortex D* value had the highest area under the curve (AUC) for discriminating between the DN and NDRD groups (AUC=0.802, sensitivity 91.3%, specificity 55.6%). Conclusion:IVIM-derived renal cortex D* value can be used non-invasively to differentiate DN from NDRD in patients with T2DM that can potentially facilitate individualized treatment planning for diabetic patients.

Objective To analyze the efficacy and safety of trastuzumab (H) and pertuzumab (P) combined with different chemotherapy regiments in neoadjuvant therapy for HER2-positive breast cancer. Methods We retrospectively analyzed the clinical data of the patients with HER2-positive breast cancer who received HP combined with chemotherapy as neoadjuvant therapy and completed surgery. The primary endpoint was total pathologic complete response (tpCR) (ypT0/isypN0), the secondary endpoints were breast pathologic complete response(bpCR) (ypT0/is) and axillary pathologic complete response (apCR) (ypN0), and the factors influencing pCR were analyzed. Results A total of 63 patients were included, of whom 23 were treated with TCbHP, 27 were treated with THP regimen, and 13 were treated with AC-THP. The overall tpCR rate was 65.1%, of which TCbHP was 73.9%, THP was 55.6%, and AC-THP was 69.2%. The tpCR rate of HR-negative patients was 79.2%, higher than that of HR-positive 56.4%. The overall bpCR rate was 69.8%, and apCR rate was 81.0%. Univariate analysis showed that HER2 status was a related factor affecting tpCR (P=0.023). The total effective rate by MRI was 87.3%. The level 3 and 4 toxicity of the TCbHP regimen was slightly higher than those of the THP and the AC-THP regimens. Conclusion HP combined with chemotherapy have achieved relatively high pCR. HER2 status is a related factor that affects tpCR. The adverse reactions are controllable.

Objective To systematically evaluate the risk of primary lung cancer in breast cancer patients. Methods A computer-based search was conducted for the English literatures about the risk of primary lung cancer in breast cancer patients in Medline, Scopus and Embase databases. Two researchers independently screened the literatures, extracted the data and assessed the risk of bias. The statistical analysis was performed using the Stata 15.5 software. Results A total of 7 references were included, and the overall risk of primary lung cancer in female breast cancer patients was slightly higher than that in the general population (SIR: 1.18, 95%CI: 1.09-1.27). Subgroup analysis showed that the risk of lung cancer was significantly increased in women aged < 50 years after diagnosis of breast cancer (SIR: 1.99, 95%CI: 1.48-2.69). Conclusion Compared with the general population, the risk of primary lung cancer is increased in female breast cancer patients, especially in young women with breast cancer.

Histone acetylation is one of the most important reactions of post-translational modification of histones, which plays an important role in the regulation of epigenetic processes. Histone deacetylase 2 as a member of type I histone deacetylases,involved in the catalytic regulation of histone and a variety of non-histone deacetylation,regulates a variety of life processes. This paper summarizes the basic structure of histone deacetylase 2 and the role of histone deacetylase 2 in various diseases,and provides a theoretical basis for conducting related studies.