Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

Objective To explore the clinicopathological and immunohistochemical features of nephrogenic adenoma(NA).Methods Clinical data of NA patients diagnosed in the Department of Pathology,Zhongshan Hospital,Fudan University from July 2016 to October 2022 were collected and analyzed to explore their clinicopathological features.Results A total of 13 NA cases were enrolled.There were 11 males and 2 females.Organs involved:ureter(n=7),bladder(n=5),bladder and ureter(n=1),renal pelvis(n=2).NA patients performed as ureteral stenosis(6/7),rough bladder wall(3/5),and renal pelvis polyp(2/2).The typical microscopical features of NA were tubular(13/13)and papillary(4/13)structures,covered with cuboidal or columnar epithelium(13/13),or a mixed hobnail-spike eosinophilic epithelium(12/13);the interstitium was loose,containing varied amounts of vasculature and inflammatory cells(13/13).Immunohistochemistry revealed specific expressions of CK7,PAX-8,CK19 and CK8.Conclusions NA is a rare neoplasm of the urinary system with unique histological features.NA has the risk of misdiagnosis and over-treatment,and the potential of recurrence and malignant conversion.The diagnosis of NA depends on pathology,and the immunohistochemistry can be helpful for its pathological diagnosis.

Objective:To investigate the diagnostic value of magnetically controlled capsule gastroscope in elderly patients with suspected upper gastrointestinal bleeding.Methods:A total of 102 patients with suspected upper gastrointestinal bleeding who underwent magnetically controlled capsule gastroscopy (MCCG) in General Hospital of Ningxia Medical University from October 2020 to September 2022 were enrolled. Patients were divided into two groups according to age: 38 patients in group A (≤65 years old) and 64 patients in group B (> 65 years old). The case data, changes of vital signs, detection of lesions and adverse reactions of the two groups were compared.Results:There were significant differences in combined diseases between group A and group B. The stomach examination time in group A was significantly shorter than that of group B (15.49±2.04 min VS 16.61±2.02 min, t=-2.685, P=0.009). There was significant difference in small intestine examination time between the two groups (331.69±14.96 min VS 337.83±14.28 min, t=-1.229, P=0.227). The incidence of adverse reactions in group A was significantly lower than that in group B [0.00%(0/38) VS 6.25%(4/64), χ2=6.186, P=0.013]. The changes of vital signs before, during and after examination were not statistically different. The detection rates of upper gastrointestinal lesions were 92.1% (35/38) and 98.4% (63/64), respectively. The positive rates of upper gastrointestinal bleeding under MCCG were 60.0% (21/35) and 50.8% (32/63), respectively. Patients with unexplained upper gastrointestinal bleeding under MCCG received small intestine examination. The detection rates of small intestinal lesions by small intestine examination were 84.6% (11/13) and 91.7% (22/24), respectively. Conclusion:MCCG demonstrates excellent diagnostic accuracy in elderly patients with suspected upper gastrointestinal bleeding. Additionally, it is safe and suitable for use in elderly patients with multiple comorbidities, allowing for concurrent small intestine examination.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

【Objective】 To investigate the clinicopathological features and prognosis of clear cell papillary renal cell carcinoma (CCPRCC). 【Methods】 The clinicopathological and follow-up data of 40 CCPRCC patients treated during Jun. 2011 and Oct.2021 were retrospectively analyzed. The prognosis was compared with that of 40 cases of clear cell renal cell carcinoma (ccRCC) and 19 cases of papillary renal cell carcinoma (PRCC) treated in the same period. Survival analysis was performed by Log-rank test and Kaplan-Meier survival curves were plotted. 【Results】 Among the 40 patients, 28 were male and 12 were female, aged 31-84 years; 38 cases had unilateral and 2 cases had bilateral tumors; 3 cases had multifocal lesions. All patients received surgery. The maximum diameter of the masses ranged from 3.0 to 95.0 mm, with an average of (27.6±18.1) mm. Pathological grade was Fuhrman 1-2 in all cases. Immunohistochemical tests were positive for CK7 and CA-IX. During the follow-up of 5-129 (average 56) months, 1 case died after bone metastasis, 2 had ipsilateral recurrence, and 1 developed primary esophageal cancer. CCPRCC patients had a significantly better prognosis than CCRCC (P<0.001) and PRCC (P=0.005) patients, while there was no significant difference in the prognosis between CCRCC and PRCC patients (P=0.93). 【Conclusions】 CCPRCC has low malignancy. The diagnosis relies on characteristic pathological and immunohistochemical features. Surgery is an effective treatment. CCPRCC has a better overall prognosis than CCRCC and PRCC.

Objective:To analyze the molecular mechanism of Zhenqi Fuzheng Capsules in the adjuvant treatment of AIDS by network pharmacology method and molecular docking technology.Methods:The active components and targets of Zhenqi Fuzheng Capsules were obtained through TCMSP, and the AIDS-related targets were obtained through GeneCards, OMIM and DrugBank databases. The intersection target PPI network was constructed through STRING 11.5 database, and Cytoscape 3.9.1 software was used for network topology analysis; Metascape database was used for GO function and KEGG pathway enrichment analysis of core targets; Cytoscape 3.9.1 was used to construct Zhenqi Fuzheng Capsules component-target-pathway network; Autodock Tools software was used to carry out molecular docking of core targets and active components.Results:Totally 31 active components and 180 targets of Zhenqi Fuzheng Capsules were screened out. TNF, IL6, AKT1, IL1B, TP53, VEGFA, RELA, EGFR and CASP3 were identified as the core targets. GO functional enrichment analysis obtained 1 436 biological processes, 53 cellular components, and 117 molecular functions. KEGG pathway enrichment analysis obtained 167 pathways, which were related to pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, and IL-17 signaling pathway was closely related. Molecular docking results showed that core targets such as AKT1 and TNF had good binding activity to quercetin, kaempferol, and luteolin.Conclusion:The main active components of Zhenqi Fuzheng Capsules in the adjuvant treatment of AIDS are quercetin, kaempferol and luteolin, which may treat AIDS through the IL-17 signaling pathway.

A patient with intermittent right lumbar pain for more than one month and aggravating for one week was reported. The right laparoscopic radical nephrectomy was performed, and fibrosarcoma of the right kidney was diagnosed. The patient refused further radiotherapy or chemotherapy and was discharged on the 11th after surgery. One year after operation, the patient underwent chest CT, and subdural tumor of right lobe of liver was detected. A surgery was performed in another hospital, and liver metastasis from right renal fibrosarcoma was diagnosed. He was alive four months after operation.

Objective:To investigate the effect of blue light combined with albumin treatment on heart, liver and nerve damage in neonatal jaundice.Methods:A total of 120 cases with neonatal jaundice in the Department of Pediatrics of Women's and Children's Hospital of Zhoushan from April 2017 to April 2018 were selected and divided into control group and observation group accorded to the random number method, with 60 cases in each group.The control group received blue light therapy.The observation group was given albumin treatment on the basis of the control group.The serum total bilirubin, bile acid, aspartate aminotransferase(AST), alanine aminotransferase(ALT), glutamyl transpeptidase(GGT), troponin(cTnT), creatine kinase isozyme(CK-MB), -hydroxybutyrate dehydrogenase(HBDH), myoglobin(MYO), S100B, neuron-specific enolase(NSE) and glial fibrillary acidic protein(GFAP) levels were determined.Results:Before treatment, there were no statistically significant differences in serum total bilirubin, bile acid, AST, ALT, GGT, cTnT, CK-MB, HBDH, MYO, S100B, NSE and GFAP levels between the two groups(all P>0.05). After treatment, the serum levels of total bilirubin[(142.67±13.02)μmol/L, (118.62±11.68)μmol/L], bile acid[(15.34±2.42)μmol/L, (7.83±2.07)μmol/L], AST[(32.17±6.34)U/L, (21.04±5.58)U/L], ALT[(25.83±4.16)U/L, (18.37±4.05)U/L], GGT[(55.24±6.37)U/L, (36.17±5.86)U/L], cTnT[(0.16±0.03)×10 -6μg/L, (0.09±0.02)×10 -6μg/L], CK-MB[(4.32±0.85)×10 -6U/L, (2.01±0.72)×10 -6U/L], HBDH[(213.04±43.61)U/L, (137.26±41.61)U/L], MYO[(22.15±3.64)×10 -6μg/L, (14.26±3.27)×10 -6μg/L], S100B[(1.41±0.28)×10 -9μg/L, (0.87±0.22)×10 -9μg/L], NSE[(15.29±2.12)×10 -9μg/L, (15.29±2.12)×10 -9μg/L] and GFAP[(19.34±0.96)×10 -9μg/L, (14.36±0.92)×10 -9μg/L] in the two groups were lower than those before treatment( t=5.214, 8.261; 7.216, 11.524; 4.027, 6.843; 3.248, 5.764; 7.129, 13.654; 6.524, 9.751; 6.854, 9.031; 4.026, 6.204; 4.521, 7.026; 4.276, 5.846; 4.812, 7.023; 7.062, 13.524, all P<0.05). The levels of serum total bilirubin, bile acid, AST, ALT, GGT, cTnT, CK-MB, HBDH, MYO, S100B, NSE and GFAP in the observation group were lower than those in the control group( t=10.651, 18.267, 10.208, 9.953, 17.066, 15.038, 16.063, 9.738, 12.490, 11.747, 17.157, 29.011, all P<0.05). Conclusion:Blue light combined with albumin treatment can alleviate heart, liver and nerve damage in neonatal jaundice.

Overuse of antibiotics in medical care and animal husbandry has led to the development of bacterial antimicrobial resistance, causing increasingly more health concern. In addition to genetic mutations and the formation of resistance, the various stresses bacteria encountered in the natural environment trigger their stress responses, which not only protect them from these stresses, but also change their tolerance to antimicrobials. The emergence of antimicrobial tolerance will inevitably affect the physiological metabolism of bacteria. However, bacteria can restore their sensitivity to drugs by regulating their own metabolism. This article reviews recent studies on the relationship between bacterial stress responses or the physiological metabolism and antimicrobial tolerance, intending to take more effective measures to control the occurrence and spread of antimicrobial resistance.
Animals ; Anti-Bacterial Agents/pharmacology* ; Anti-Infective Agents ; Bacteria/genetics* ; Drug Resistance, Bacterial ; Stress, Physiological