Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Small Cell ; metabolism ; pathology ; therapy ; Cardia ; Chemotherapy, Adjuvant ; Chromogranin A ; metabolism ; Female ; Follow-Up Studies ; Gastrectomy ; methods ; Humans ; Male ; Middle Aged ; Phosphopyruvate Hydratase ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; therapy ; Survival Rate

Objective To explore the influence of the lactation exposure to fluoxetine on offspring's behavior and serotonin transporter (SERT) and tryptophan hydroxylase (TPH). Methods Six SD pregnant rats were randomly divided into 2 groups (n=3 each group). Experimental maternal rats were intraperitoneally injected with fluoxetine at a dose of 12 mg/kg from postnatal day 5 to 21. The control group were injected with the same amount of normal saline. In infancy, the offspring's weight, hair length, eye opening and auditory development were measured. The free suspension test and bur?ied food pellets test were applied to evaluate the offspring's behaviors. After postnatal day 21, all the offspring were wean. At early childhood (P35d) and adulthood (P75d), 6 offspring rats from each group were executed to examine SERT and TPH in the prefrontal cortex by immunohistochemistry. Results The offspring's weight of experimental group was significantly lower than control group (P<0.05). The sensitivity of auditory in experimental group was significantly higher than control group (P<0.01). The time of free suspension in experimental group significantly was decreased comparing to control group (P<0.01). The SERT and TPH in prefrontal cortex was significantly lower in experimental group than those in control group either at childhood (P35d) or at adulthood (P75d) (P<0.05). Conclusion Lactation exposure to fluoxetine re?sults in offspring's abnormal development and behaviors through down-regulation of SERT and TPH in the prefrontal cor?tex.

BACKGROUNDProprioception plays an important role in knee movements. Since there are controversies surrounding the overall recovery time of proprioception following surgery, it is necessary to define the factors affecting proprioceptive recovery after anterior cruciate ligament (ACL) reconstruction and to investigate the relationship between proprioception and muscle strength.

METHODSA total of 36 patients who had their ACL reconstructed with a semitendinosus/gracilis graft (reconstructed group: 6 months post-surgery) and 13 healthy adults without any knee injury (control group) were included in the study. Knee proprioception was evaluated with a passive reproduction test. Isokinetic strength was measured using the Biodex System. Statistical analysis was used to compare proprioception of the reconstructed group versus the control group, and to define causal factors, including sex, hamstring/quadriceps ratio, and the course of injury before reconstruction. We also investigated the correlation between the passive reproduction error and quadriceps index.

RESULTSThere was a significant difference in proprioception between the reconstructed and control groups (P < 0.05). When the course of injury before reconstruction was less than 4 months, there was a linear correlation with proprioception 6 months after the operation (r = 0.713, P < 0.05). There was a positive correlation between post-surgery proprioception and the quadriceps index at 6 months post-surgery.

CONCLUSIONSImpaired knee proprioception is observed 6 months after ACL reconstruction. Within 4 months of injury, early undertaking of reconstruction is associated with better proprioception outcome. Patients with enhanced proprioception have a better quadriceps index.

Adolescent ; Adult ; Anterior Cruciate Ligament ; pathology ; physiopathology ; surgery ; Female ; Humans ; Knee Injuries ; pathology ; physiopathology ; surgery ; Male ; Proprioception ; physiology ; Reconstructive Surgical Procedures ; methods ; Recovery of Function ; Young Adult

OBJECTIVETo elucidate the potential molecular mechanism responsible for the early time of tumor promotion, gene expression profile was studied in the transformed BALB/c 3T3 cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA).

METHODSThe two-stage cell transformation model was established by using the initiator of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and promoter of TPA. Cell proliferation was measured by trypan blue staining and cell cycle analysis was carried out by flow cytometry assay. A cDNA microarray representing 1 152 genes was used to investigate the gene expression profiles of BALB/c 3T3 cells exposed to TPA at 4 h and 24 h respectively.

RESULTSTPA could effectively inhibit cell proliferation and induce the G1 and S cell cycle arrested in the early time. Moreover 19 genes were found differentially expressed at least twofold in the TPA treated cells as compared with the control cells, 9 of them were upregulated and 10 downregulated. Most of the differentially expressed genes were involved in cell proliferation, differentiation or apoptosis, and related to ras or p53 signal transduction pathway.

CONCLUSIONTPA could influence the transcriptional expression of some genes related to cell cycle modulation and ultimately result in the cell growth arrest.

Animals ; Apoptosis ; drug effects ; genetics ; BALB 3T3 Cells ; Cell Cycle ; drug effects ; genetics ; Cell Differentiation ; drug effects ; genetics ; Cell Proliferation ; drug effects ; Cell Transformation, Neoplastic ; drug effects ; genetics ; Flow Cytometry ; Gene Expression ; drug effects ; Gene Expression Profiling ; Methylnitronitrosoguanidine ; pharmacology ; Mice ; Oligonucleotide Array Sequence Analysis ; methods ; Tetradecanoylphorbol Acetate ; analogs & derivatives ; pharmacology

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

China ; Humans ; Otolaryngology

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

The combination of ginkgo ketoester tablet - donepezil (GD) is a popular combination commonly used in clinic for the treatment of Alzheimer's disease. To evaluate the learning and memory improving ability of different proportions of the two drugs. We optimized the ratio of GD for treatment of dementia using a mouse model. Dementia was induced by multiple neuronal damages in mice. The experimental protocols were approved by the Animal Experimental Ethical Committee of Nanjing University of Chinese Medicine and all the procedures were strictly conducted in accordance with ethical principle of animal use and care. Morris water maze, brain hematosylin-eosin staining and the changes of the neurotransmitters and related enzymes in the plasma or brain tissues were tested to determine the effect of GD on dementia mice. The results showed that the dementia mice were significantly different from the normal group in terms of behavior, pathological sections and related indicators. Compared to the dementia mice, partial administration groups could improve learning and memory ability as well as indexes in the blood and brain tissues. Both the principal component analysis and multi-attribute comprehensive index methods were used to comprehensively evaluate the total effect of GD on anti-dementia. The results showed that the combination of two drugs at the dose of 0.5 to 1 times was in a dose-effect relationship, and the dose of 1 (the clinical equivalent) had the best treatment effect. Then based on the optimal dose, GD 1∶1 had best effect, which was consistent with the clinical use of two drugs. This provides scientific basis for more effective application of the compatibility between ketoester tablet and donepezil for modern clinic medicine.