Correlation between the intrahepatic inflammatory pathogenesis and the TCM theory of liver collateral injury by toxins in patients of type 2 diabetes mellitus (T2DM) with insulin resistance (IR) was investigated, to elucidate that removing toxins, dredging collateral and modulating Gan could be one of the effective approaches for inhibiting intrahepatic inflammation mechanism of T2DM with IR.
Chemokine CCL2 ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; metabolism ; physiopathology ; Diagnosis, Differential ; Humans ; Inflammation ; etiology ; metabolism ; physiopathology ; Insulin Resistance ; Liver ; metabolism ; pathology ; physiopathology ; Medicine, Chinese Traditional ; NF-kappa B ; metabolism

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disease caused by SLC25A13 gene mutations, and is characterized by delayed jaundice clearance, liver dysfunction, and elevated aminoacidemia. The confirmed diagnosis depends on gene analysis. Citrin deficiency is one of the important causes of neonatal intrahepatic cholestasis in China. Recently more and more researches about NICCD were reported. The paper summarized the epidemiology, pathogenesis, clinical characteristics, and progresses in diagnosis and treatment of NICCD.

Oxidative stress is a redox imbalance in the body, which is one of the important factors leading to tissue damage and diseases. The nuclear factor E2-related factor 2 (Nrf2)-Kelch like ECH-associated protein 1 (Keap1) signaling pathway is not only an important defense system against oxidative damage, but also one of the key signaling pathways of the antioxidant capacity. Numerous studies have shown that targeting the Keap1-Nrf2 signaling pathway to activate Nrf2 has become an effective strategy for the treatment of oxidative stress and related diseases. Using small molecules to directly block the Keap1-Nrf2 protein-protein interaction (PPI) is one of the important directions for activating Nrf2 and exerting the cytoprotective effect, which can avoid the potential side effects of covalent modification of Nrf2. On the other hand, the Keap1 is an efficient E3 ubiquitin ligase that has been used in the design of proteolysis targeting chimeras (PROTACs). This review summarizes the research progresses of Keap1-Nrf2 protein interaction inhibitors and degraders based on the Keap1 E3 ubiquitination system in recent years.

Alkaloids ; chemistry ; isolation & purification ; pharmacology ; Animals ; Antineoplastic Agents ; pharmacology ; Antiviral Agents ; pharmacology ; Carbolines ; chemistry ; isolation & purification ; pharmacology ; Humans ; Molecular Structure ; Urochordata ; chemistry

PURPOSE: The aim of the study was to evaluate the efficacy and safety of combining sorafenib with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, American Society for Clinical Oncology abstracts, and European Society for Medical Oncology abstracts were searched. Randomized clinical trials that compared the efficacy and safety of sorafenib plus chemotherapy in patients with HER2-negative advanced breast cancer with placebo plus chemotherapy were eligible. The endpoints were progression-free survival (PFS), overall survival (OS), time to progression (TTP), duration of response (DOR), overall response rate (ORR), clinical benefits, and adverse effects. The meta-analysis was performed using Review Manager 5.2.6 (The Nordic Cochrane Centre), and the fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneity was found (p<0.1), further analysis (subgroup analysis, sensitivity analysis, or random-effect model) was performed to identify the potential cause. The results are expressed as hazard ratios or risk ratios, with their corresponding 95% confidence intervals. RESULTS: The final analysis included four trials comprising 844 patients. The results revealed longer PFS and TTP, and higher ORR and clinical benefit rates in patients receiving sorafenib combined with chemotherapy compared to those receiving chemotherapy and placebo. OS and DOR were similar in the two groups. Meanwhile, the incidence of some adverse effects, including hand-foot skin reaction/hand-foot syndrome, diarrhea, rash, and hypertension, were significantly higher in the sorafenib arm. CONCLUSION: Sorafenib combined with chemotherapy may prolong PFS and TTP. This treatment was associated with manageable toxicities, but frequent dose interruptions and reductions were required.
Arm ; Breast Neoplasms* ; Breast* ; Diarrhea ; Disease-Free Survival ; Drug Therapy* ; Exanthema ; Humans ; Hypertension ; Incidence ; Medical Oncology ; Odds Ratio ; Population Characteristics ; Receptor, Epidermal Growth Factor ; Skin ; Treatment Outcome

OBJECTIVETo investigate the allocation and management of large medical equipment (LME) in Xuzhou, Jiangsu Province, China, in order to make the best use of LME to meet the medical needs of local people.

METHODSThe research collected data from all hospitals that have LME in Xuzhou using questionnaire; 38 (97.4%) hospitals returned the questionnaire.

RESULTSIn Xuzhou, there are a total of 71 pieces of LME, each serving 126 600 people in an area of 163 km(2). Sixty-two percent of them are allocated in urban areas, with Gini coefficient at 0.52, indicating imbalance and biased allocation of LME.

CONCLUSIONThe allocation of LME in Xuzhou is out of control and unfairly allocated.

China ; Equipment and Supplies ; Hospitals ; Medical Laboratory Science ; Surveys and Questionnaires

OBJECTIVETo investigate the clinical characteristics and prognosis of different breast cancer molecular subtypes.

METHODSClinicopathological and follow-up data of 1153 cases of operable breast cancer were analyzed retrospectively. Their molecular subtypes were categorized as luminal A, luminal B, Her-2 over-expressing and basal-like subtypes, based on detection of ER, PR, Her-2 expression. The correlation of prognosis of different molecular subtypes with age, tumor size, lymph node status and clinical staging was analyzed.

RESULTSAmong the 1153 cases, 791 cases (68.6%) were of luminal A subtype, 50 cases (4.3%) luminal B subtype, 53 cases (4.6%) Her-2(+)subtype, and 259 cases (22.5%) basal-like subtype. There were no statistically significant differences among different molecular subtypes regarding the age, tumor size, lymph node status, and clinical stage. 1006 cases had complete follow-up data and the analysis showed that distant metastasis of Her-2 over-expressing subtype was significantly higher than that in other subtypes (P = 0.005), but the differences of local recurrence rate in different molecular subtypes was not statistically significant (P > 0.05). Kaplan-Meier method was used to analyze the survival prognosis of different molecular subtypes, showing both DFS rate and OS rate of Her-2 over-expressing subtype were the lowest, with a statistically significant difference (Log rank test, P < 0.05). Univariate and multivariate analyses showed that molecular typing and lymph node status were independent prognostic factors affecting both DFS and OS.

CONCLUSIONSHer-2 over-expressing subtype has the worst prognosis. Molecular subtypes may provide important information to predict the prognosis of breast cancer and might be an important basis for individualized treatment of breast cancer in future.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; classification ; metabolism ; pathology ; therapy ; Carcinoma, Ductal, Breast ; classification ; metabolism ; pathology ; therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Mastectomy ; methods ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Survival Rate ; Young Adult

An introduction of the design, features and contraceptive principle of an oviduct contraceptive plug is given in this paper. The plug is made of polyethylene, based on the oviductal morphology. It can be introduced and removed by a hysteroscope and is expected to be a transcervical, implantable and permanent intratubal contraceptive device.
Contraceptive Devices, Female ; Equipment Design ; Polyethylene ; Sterilization, Tubal ; instrumentation

OBJECTIVE Tissue plasminogen activator (tPA) is the only approved pharmaco-logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans-formation that follows tPA treatment. Here, we determined whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, affects tPA-induced haemorrhagic transformation. METHODS Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.When the filament was removed for reperfusion, tPA was infused via the tail vein.A single dose of NMN was injected i.p.(300 mg·kg-1).Mice were killed at 24 h post ischaemia, and their brains were evaluated for brain infarction, oedema, haemoglobin content, apoptosis, neuroinflammation, blood-brain barrier (BBB) permeability, the expression of tight junction proteins(TJPs)and the activity/expression of MMPs. RESULTS In the mice infused with tPA at 5 h post ischaemia, there were significant increases in mortality, brain infarction, brain oedema, brain haemoglobin level, neural apoptosis, Iba-1 staining (microglia activation) and myeloperoxidase staining (neutrophil infiltration). All these tPA-induced alterations were significantly prevented by NMN administration. Mechanistically, the delayed tPA treatment increased BBB permeability by down-regulating TJPs, including claudin-1, occludin and zonula occludens-1,and enhancing the activities and protein expression of MMP9 and MMP2. Similarly, NMN administration partly blocked these tPA-induced molecular changes. CONCLUSION Our results demonstrate that NMN ameliorates tPA-induced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.

OBJECTIVETo investigate lipoprotein lipase (LPL) and serum thymidine kinase (TK) levels in chronic lymphocytic leukemia (CLL) and their correlations with other prognostic factors.

METHODSLPL expression level in peripheral blood samples of 58 CLL patients was detected by semi-quantitative reverse transcription PCR (RT-PCR). Serum TK1 level in 39 CLL patients was detected by enhanced chemiluminescence (ECL) and TK monoclonal antibody (Anti-TK mAb). IgVH mutation status was detected by multiplex PCR and sequencing of purified PCR products. The expression of ZAP-70 protein and CD38 were determined by flow cytometry . Panel probes and fluorescence in situ hybridization (FISH) were used to detect cytogenetic aberrations.

RESULTSThe median LPL expression level in CLL was 0.26 (0 -6.29), while undetectable in normal controls. LPL expression level was significantly correlated with IgVH mutation status, Binet stages, CD38 and cytogenetic aberrations. Patients with unmutated IgVH genes had higher LPL than those with IgVH mutations (P = 0.010). Patients in Binet stage B and C had higher LPL than those in stage A (P = 0.011). LPL level was higher in patients with CD38 > or = 30% (P = 0.001). Higher LPL level was found in patients with unfavorable cytogenetic aberrations (deletion in 17p13 or 11q22) than those with favorable cytogenetics (deletion in 13q as the sole abnormality) (P = 0.002). LPL level was not significantly correlated with sex, age, and ZAP-70 protein (P > 0.05). The level of TK1 was higher in CLL patients than that in normal control (P < 0.05). Patients with higher level of absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), unmutated IgVH genes and ZAP-70 had higher levels of TK1 than those with lower level of ALC, LDH, mutated IgVH genes and ZAP-70 (P = 0.018, P = 0.018, P = 0.030 and P = 0.038, respectively). TK1 level had no correlation with sex, age, Binet stages, CD38, and cytogenetic aberrations (P > 0.05).

CONCLUSIONSLPL expression and serum TK1 levels significantly correlate with other CLL prognostic factors and could be predictive markers for IgVH mutation status. LPL and serum TK1 might be applied to the assessment of prognosis in CLL patients.

ADP-ribosyl Cyclase 1 ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; enzymology ; metabolism ; Lipoprotein Lipase ; blood ; Male ; Middle Aged ; Mutation ; Thymidine Kinase ; blood ; ZAP-70 Protein-Tyrosine Kinase ; metabolism