[Impact of immediate breast reconstruction on the onset of adjuvant chemotherapy and on the postoperative complications].

Objective: To explore the impact of immediate breast reconstruction on the onset of adjuvant chemotherapy and on the postoperative complications. Methods: We retrospectively analyzed the clinical data from female breast cancer patients treated by either modified radical mastectomy with immediate breast reconstruction(IBR) ( n=108) or modified radical mastectomy alone(n=115), followed by adjuvant chemotherapy at our department between January 2011 and December 2012. Results: There was no significant difference in the overall complication rates between the IBR group and modified radical mastectomy group (49.1% vs. 52.2%, P=0.87). However, more secondary surgery was applied in the IBR group than the modified radical mastectomy group (13.0% vs. 1.7%, P=0.001). However, the incidence of hematoma in the modified radical mastectomy group was significantly higher than the IBR group (17.4% vs. 4.6%, P=0.003). There was a significant difference in the onset of adjuvant chemotherapy between the IBR group and modified radical mastectomy group (21 days vs. 11days, P<0.001). Conclusions: Immediate breast reconstruction has no significant impact on the overall complication rate, but increases the incidence of secondary surgery, especially after the initiation of chemotherapy. In addition, it slightly delays adjuvant chemotherapy in the patients.

Single-nucleotide polymorphism microarray-based preimplantation genetic diagnosis is likely to improve the clinical outcome for translocation carriers.

STUDY QUESTION: Is preimplantation genetic diagnosis (PGD) for translocation carriers more effective when done with a single-nucleotide polymorphism (SNP) array using trophectoderm (TE) biopsy and frozen embryo transfer (FET) compared with traditional PGD based on fluorescence in situ hybridization (FISH-PGD) using blastomere biopsy and fresh embryo transfer? SUMMARY ANSWER: The procedure using the SNP array combined with TE biopsy and FET significantly improves the clinical pregnancy rate for translocation carriers. The miscarriage rate also slightly decreases. WHAT IS KNOWN ALREADY: FISH-PGD has been widely used in translocation carriers but the clinical outcomes have not been ideal. SNP arrays can detect both chromosome segmental imbalances and aneuploidy, and may overcome the limitations of FISH in PGD for translocation carriers. STUDY DESIGN, SIZE AND DURATION: This was a retrospective study of 575 couples with chromosomal translocations, including 169 couples treated by SNP-PGD between October 2011 and August 2012, and 406 couples treated by FISH-PGD between January 2005 and October 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was set in an IVF center at the Reproductive and Genetic Hospital of CITIC-Xiangya, China. In total, 169 couples underwent SNP analysis, including 52 Robertsonian translocation carriers and 117 carriers of reciprocal translocations. Blastocysts (n = 773) were biopsied and FET was carried out on the balanced embryos. Four hundred and six couples underwent FISH-PGD, including 149 Robertsonian translocation carriers and 257 reciprocal translocation carriers. In total, 3968 embryos were biopsied and balanced embryos were transferred fresh. The SNP-PGD results and clinical outcomes were compared with those of FISH-PGD. MAIN RESULTS AND THE ROLE OF CHANCE: Reliable SNP-PGD results were obtained for 717 out of 773 (92.8%) biopsied blastocysts. The proportions of normal/balanced embryos, embryos with translocation-related and translocation-unrelated abnormalities, the median number of embryos per patient, the ongoing pregnancy rate per embryo transfer and the miscarriage rate were 58, 23, 19, 2, 69 and 12%, respectively, for Robertsonian translocation carriers and 36, 52, 12, 1, 74 and 11%, respectively, in reciprocal translocation carriers. Reliable FISH-PGD results were obtained for 3452 out of 3968 (87.0%) biopsied embryos. The proportions of normal/balanced embryos, unbalanced embryos, the median number of embryos per patient, the ongoing pregnancy rate per transfer and the miscarriage were 36, 64, 3, 38 and 17%, respectively, for Robertsonian translocation carriers and 20, 80, 1, 39 and 16%, respectively, for reciprocal translocation carriers. Thus, SNP-PGD achieved a higher pregnancy rate but a lower miscarriage rate than FISH-PGD. There were no significant differences in maternal age, basal endocrine level and the average number of retrieved oocytes and good-quality D3 embryos in the SNP-PGD group compared with the FISH-PGD group. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study with the two groups treated in different periods; therefore, there is a chance of sample bias and a possibility that the results were influenced by other factors that changed over time. Furthermore, the two treatment protocols differ in several respects and we cannot say which makes the greatest contribution to the difference in success. Complete pregnancy outcomes of SNP-PGD have not been obtained as some embryos have not been transferred yet. We cannot exclude differences between the final data and the data in the present manuscript. WIDER IMPLICATIONS OF THE FINDINGS: The adoption of SNP-PGD combined with TE biopsy and FET may significantly improve the clinical pregnancy rate, and decrease the miscarriage rate after PGD for translocation carriers.

[Effect of early tocilizumab intervention on patients with cytokine release syndrome following chimeric antigen receptor T cell therapy].

Objective: This study aimed to evaluate the effect of early tocilizumab intervention to relieve cytokine release syndrome (CRS) following chimeric antigen receptor T cell (CAR-T) therapy. Methods: Twenty-two patients with acute lymphoblastic leukemia who received tocilizumab to relieve CRS response after CAR-T cell infusion in our research center from October 2015 to July 2021 were retrospectively analyzed. According to the timing of tocilizumab intervention, patients were divided into the conventional and early intervention groups. Patients who received tocilizumab treatment after sustained high fever for 4 h were included in the early intervention group. The clinical data, CRS grade, and event-free survival (EFS) between the two groups were evaluated. Results: Compared with patients who used tocilizumab after severe CRS, no patients in the early intervention group died from CRS, and there was no increased risk of neurotoxicity. Eleven patients (84.62%) achieved complete remission with minimal residual lesions. The median EFS of patients in the early intervention and conventional groups was 2 (95% CI 0-5) and 7 (95% CI 3-11) months, respectively. Conclusion: Early tocilizumab intervention in patients with CRS reduces severe CRS and provides a more optimized therapeutic strategy for CRS caused by CAR-T cell therapy.

[Comparison of efficacy between laparoscopic and open proximal gastrectomy with double-tract reconstruction for Siewert type â ¡ and â ¢ adenocarcinoma of the esophagogastric junction].

Objective: To compare the efficacy between laparoscopic and open proximal gastrectomy with double-tract reconstruction for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) 18 to 80 years old; (2) Siewert II and III AEG was confirmed by preoperative gastroscopy and biopsy, which could not be resected by endoscopy; patients undergoing radical proximal gastrectomy with double-tract reconstruction; (3) contrast-enhanced abdominal CT staging was cT1-2N0M0; (4) Eastern Cooperative Oncology Group (ECOG) physical status score <2 points, American Association of Anesthesiologists (ASA) grade 1 to 2; (5) patients agreed to perform proximal gastrectomy and signed an informed consent. Those who had undergone neoadjuvant radiochemotherapy, suffered from serious mental diseases and had incomplete data were excluded. According to the above criteria, clinical data of 84 consecutive patients with Siewert II and III AEG undergoing surgery at General Surgery Department of The Affiliated Tumor Hospital of Zhengzhou University from October 2010 to December 2018 were collected and analyzed. Of 84 patients, 61 underwent open proximal gastrectomy with double-tract reconstruction (OPG group), while 23 underwent laparoscopic proximal gastrectomy with double-tract reconstruction (LPG group). The perioperative complications and postoperative reflux esophagitis of two groups were compared. A P-value of <0.05 was considered to be statistically significant. Results: Among 84 cases, 74 were male and 10 were female. There were 43 cases of Siewert type II and 41 cases of Siewert type III. There were no significant differences in age, gender, body mass index, comorbidities, Siewert type, and tumor staging between the two groups (all P>0.05). As compared to the OPG group, the LPG group had longer operation duration [(223±21) minutes vs. (161±14) minutes, t=15.352, P<0.001], less intraoperative blood loss [195 (150, 215) ml vs. 208 (192, 230) ml, Z=2.143, P=0.032], and shorter time to flatus [(2.8±0.7) days vs. (3.3±0.9) days, t=2.477, P=0.015]. There were no significant differences in the number of harvested lymph nodes, time to the first meal and postoperative hospital stay between the two groups (all P>0.05). Postoperative complications developed in 2 cases (8.7%, 1 case each for anastomotic leakage and intestinal obstruction) in the LPG group and 5 cases (8.2%, 1 case each for anastomotic leakage, anastomotic bleeding, and anastomotic stenosis, 2 cases of incision infection) in the OPG group (χ(2)=5.603, P=0.231). The median follow-up was 41.2 (12.8-110.5) months. One patient (1.6%,1/61) had obvious reflux symptoms in the OPG group, compared with none in the LPG group (χ(2)=0.644, P=0.422). Esophagitis occurred in 1 case (4.8%, 1/21) in LPG group, compared with 4 patients (7.1%, 4/56) in the OPG group, without significant difference between the two groups (χ(2)=0.505, P=0.477). Conclusion: Laparoscopic proximal gastrectomy with double-tract reconstruction is safe and feasible without increasing the risk of postoperative complication and reflux esophagitis.

The glutamatergic projection from the prefrontal cortex to the nucleus accumbens core is required for cocaine-induced decreases in ventral pallidal GABA.

Cocaine-primed reinstatement of drug seeking is associated with a decrease in extracellular GABA in the ventral pallidum (VP). The present study investigated the neural mechanism of this cocaine-induced decrease in VP GABA by determining if activity of the glutamatergic projection from the medial prefrontal cortex (PFC) to the nucleus accumbens is required for the effect. Microdialysis was performed to measure extracellular GABA in the VP while simultaneously, either a combination of the GABA agonists baclofen and muscimol was microinjected into the PFC, or the AMPA/kainate glutamate receptor antagonist CNQX was microinjected into the accumbens core. Inhibition of the PFC with GABA agonists and blockade of AMPA glutamate receptors in the accumbens core were both sufficient to prevent the cocaine-induced decrease in VP GABA, further implicating increased activity of the cortico-striato-pallidal circuit in relapse to drug seeking.

Sumoylation in Lens Differentiation and Pathogenesis.

Sumoylation, a post-translational modification discovered over a decade ago, turns out to be a very important regulatory mechanism mediating multiple cellular processes. Recent studies from our laboratory and others also revealed that it plays a crucial role in regulating both differentiation and pathogenesis of the ocular lens. This review will summarize these progresses.

Location and phylogenetic analysis of the region immediately upstream of the granulin gene of the Clostera anachoreta granulovirus.

The region immediately upstream of the granulin gene from Clostera anachoreta granulovirus (ClanGV) was identified from hybridization experiments and sequenced. The sequence of 5122nt EcoRI restriction fragment was presented and compared with the equivalent area in other GVs. Database searches showed that this region contained three open reading frames (ORFs) similar to the baculovirus genes (egt, fgf and me53, respectively) and four ORFs unique to ClanGV genome. Phylogenetic trees of the baculovirus genes egt and me53 were constructed. These analyses indicated that ClanGV genes may be more closely related to CfGV, CpGV, ClGV, PoGV and AoGV than to PxGV and XcGV.

The Male Abnormal Gene Family 21 (Mab21) Members Regulate Eye Development.

The male abnormal gene family contains 3 members, named mab21l1, mab21l2 and mab21l3. Since their first discovery in C. elegans, homologues of mab21l1 and mab21l2 have been found in Drosophila, Zebrafish, Xenopus, chicken, mouse and human. A number of studies have revealed that mab21 gene family members, mab21l1 and mab21l2, play important roles in regulating eye development. Here, we review the functions of the mab genes in regulating ocular development.

Characterization of the RNA-binding domain in the Dendrolimus punctatus cytoplasmic polyhedrosis virus nonstructural protein p44.

Dendrolimus punctatus cytoplasmic polyhedrosis virus (DpCPV-1) belongs to the Cypovirus genus in the Reoviridae family. The ORF of genome segment 8 (S8) of DpCPV-1 was cloned into vector pMAL-c2X and used to express a 44kDa protein (p44) in E. coli, which was detected by Western blotting. The gel mobility shift assays showed that p44 had ssRNA-binding activity. Competitive assay indicated that this protein only bind to ssRNA and could not interact with DNA and dsRNA. The binding of p44 to ssRNA is sequence non-specific. To identify the domain(s) important for RNA binding of the protein, a number of deletions were made. These truncated proteins were expressed in E. coli and purified. The affinity of each truncated protein towards ssRNA was then assayed by electrophoretic mobility shift assays and northwestern blot. The results indicated that glutamic acid-rich domain in the central region of p44 from residues 104 to 201 was the ssRNA-binding domain.

Characterization and partial genome sequence analysis of Clostera anachoreta granulovirus.

The morphological and biological properties as well as partial genomic sequencing of a granulovirus isolated from Clostera anachoreta (Lepidoptera: Notodontidae), C. anachoreta granulovirus (ClanGV), were carried out. The ovoidal occlusion bodies were 337 nm x 170 nm in size, and each granule contained one single rod-shape virion, with a mean size of 250 nm x 46 nm. Granulin had a molecular weight of approximately 30 kDa. ClanGV genome size was estimated as 104.34 kb based on the restriction fragments. The restriction pattern of the ClanGV genome was different from other GVs. A restriction fragment genomic library of ClanGV genome was constructed. The library consisted of nine SalI fragments, seven HindIII fragments and seven EcoRI fragments. One 4.8 kb fragment of the genome, digested by SalI, was sequenced and analyzed. This region was composed of eight unknown ORFs, two baculoviruses homologous gene (vp1054 and lef10) and partial sequence of lef-8. The unknown ORFs included three unique to ClanGV, the other five ORFs were related to baculoviruses. The ORFs, located within this restriction fragment, were compared to homologues in other GVs. The results indicated that ClanGV, CpGV, ClGV, AoGV and PoGV had similar arrangement and orientation of the homologous ORFs. Phylogenetic analysis of VP1054 proteins from 20 baculoviruses indicated that ClanGV was more closely related to CpGV, ClGV, AoGV and PoGV than to other baculoviruses.

Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease.

HupA is a potent, reversible and selective inhibitor of AChE with a rapid absorption and penetration into the brain in animal tests. It exhibits memory-enhancing activities in animal and clinical trials. Compared to tacrine and donepezil, HupA possesses a longer duration of action and higher therapeutic index, and the peripheral cholinergic side effects are minimal at therapeutic doses. This review article deals with a comprehensive survey of the progress in chemical and pharmacological studies of HupA including the isolation and structure elucidation, pharmacological actions, total synthesis, SAR studies and the future development of HupA. Recently, it has been reported that HupA could reduce neuronal cell death caused by glutamate. The dual bio-activities of HupA would further enhance its value and potentiality as the therapeutic agent for Alzheimer s disease.

Acute and chronic studies with the anticholinesterase Huperzine A: effect on central nervous system cholinergic parameters.

High affinity choline transport, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were assessed in rats after acute and chronic administration of the AChE inhibitor Huperzine A. Acute treatment: Forty-five min after a single injection of Huperzine A (0.5 mg/kg i.p.) the activity of AChE was significantly decreased by 15-30% in hippocampus, striatum and septum. The activity of ChAT was not altered. In the hippocampus high affinity choline transport was attenuated by 25%, whereas no effect in the striatum was observed. After 90 min, both inhibition of AChE and attenuation of high affinity choline transport had returned to control values. A dose of 0.1 mg/kg (i.p.) did not produce significant effects. Similar results were obtained with physostigmine (0.25 mg/kg), although the duration of inhibition of AChE was shorter than that with Huperzine A. Chronic treatment: After 5 days (twice a day), at 0.5 mg/kg, the activity of AChE was significantly reduced by 20-30% in every region of the brain studied. High affinity choline transport in the hippocampus was reduced by 28%, 45 min after the last injection, but in the striatum there was no effect. The activity of ChAT was not affected in any region of the brain studied. Thus, acute or chronic treatment with Huperzine A: did not alter ChAT; reduced high affinity choline transport in the hippocampus in a transient manner; and had a longer duration of action as an AChE inhibitor than physostigmine. Moreover, tolerance to low-toxicity doses of Huperzine A was minimal, contrary to what has been observed with other inhibitors of AChE.

Natural and synthetic Huperzine A: effect on cholinergic function in vitro and in vivo.

Huperzine A has been shown to be useful in the treatment of symptoms of dementia of the Alzheimer type. Our initial attempts to synthesize (-)Huperzine A resulted in the racemic mixture of (+/-)Huperzine A. We have therefore compared the in vitro and in vivo effects of (+/-)Huperzine A with those of (-)Huperzine A in rats. The results indicate a similar biological mechanism of action between the two, but that the racemic mixture of (+/-)Huperzine A has a weaker biological activity than the natural product (-)Huperzine A, presumably due to the presence in the mixture of (+)Huperzine A, which is considerably less potent than the (-)isomer.

Huperzine A attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells.

The present studies investigated effects of huperzine A (HupA), a selective acetylcholinesterase (AChE) inhibitor and promising anti-dementia agent, on hydrogen peroxide (H2O2)-induced apoptosis and the expression of apoptosis-related genes in rat pheochromocytoma line PC12 cells. Transient exposure of the cells to H2O2 (100 microM) triggered a typical apoptosis as evidenced by chromatin condensation, nuclei fragmentation and DNA laddering. RT-PCR studies showed up-regulated p53 and Bax but lowered Bcl-2 mRNA levels with H2O2 treatment. The results were further confirmed at protein levels by immunocytochemistry with specific antibodies. Preincubation with HupA (1 microM) significantly prevented the cells from apoptosis, attenuated H2O2-induced over-expression of Bax and p53, and rehabilitated the level of Bcl-2. The present findings suggest that HupA exerts significant protection against H2O2-induced apoptosis, possibly through improving expression of apoptosis-related genes.

Huperzine A, a novel promising acetylcholinesterase inhibitor.

The effects of huperzine A on memory impairments induced by scopolamine were evaluated using a radial maze task and inhibition of cholinesterase in vitro compared with the effects of E2020 and tacrine. Scopolamine (0.2 mg kg-1) significantly impaired spatial memory in rats. Huperzine A (0.1-0.4 mg kg-1, p.o.), E2020 (0.5-1.0 mg kg-1, p.o.) and tacrine (1.0-2.0 mg kg-1, p.o.) could reverse these scopolamine-induced memory deficits. The ratios of huperzine A, E2020 and tacrine for butyrylcholinesterase:acetylcholinesterase determined by a colourimetric method were 884.57, 489.05, and 0.80, respectively. The results demonstrated that huperzine A was the most selective acetylcholinterase inhibitor, and improved the working memory deficit induced by scopolamine significantly better than did E2020 or tacrine, suggesting it may be a promising agent for clinical therapy of cognitive impairment in patients with Alzheimer's Disease.

Huperzine A protects rat pheochromocytoma cells against oxygen-glucose deprivation.

The effect of huperzine A (HupA) on oxygen-glucose deprivation (OGD)-induced injury was investigated in the rat pheochromocytoma cell line PC12. OGD for 3 h and reoxygenation for 24 h triggered apoptosis characterized by chromatin condensation, nucleus fragmentation and DNA laddering. The temporal profile of c-jun, p53, bcl-2 and bax mRNA after OGD indicated that these genes played important roles in apoptosis. Pre-incubation of the cells for 2 h with 1 microM HupA significantly attenuated apoptosis. The same treatment also reduced the up-regulation of c-jun and bax as well as the down-regulation of bcl-2. These data suggest the ability of HupA to attenuate apoptosis induced by OGD may result from its capability to alter the expression of apoptosis-related genes.

Reversal of scopolamine-induced deficits in radial maze performance by (-)-huperzine A: comparison with E2020 and tacrine.

The effects of (-)-huperzine A ((5R,9R,11E)-5-amino-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5, 9-methanocycloocta[b]pyridin-2(1H)-one), and of the hydrochloride salt of E2020 ((R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methyl piperidine) and tacrine (9-amino-1,2,3,4-tetrahydroacridine), on the scopolamine-induced memory deficits in rats were compared in a radial maze, using a 4-out-of-8 baiting procedure. Scopolamine (0.15 mg/kg, i.p.) caused significant impairment in the rats' ability to fulfil the radial maze task. (-)-Huperzine A (0.2-0.4 mg/kg, p.o.; 0.1-0.4 mg/kg, i.p.) had greater efficacy than E2020 (0.6-0.9 mg/kg, p.o.; 0.3-0.6 mg/kg, i.p.) and tacrine (1.5-2.5 mg/kg, p.o.; 0.3-0.6 mg/kg, i.p.) on the improvement of scopolamine-induced working and reference memory errors, respectively. There appeared to be an inverse bell-shape dose-dependent effect for all three compounds tested. The compared data demonstrate that (-)-huperzine A is the most potent and orally active acetylcholinesterase inhibitor of the three, and fits more closely the established criterions for an ideal acetylcholinesterase inhibitor to be used in clinical studies.

Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1-40) in rat.

Huperzine A, a promising therapeutic agent for Alzheimer's disease, was examined for its potential to antagonize the deleterious neurochemical, structural, and cognitive effects of infusing beta-amyloid protein-(1-40) into the cerebral ventricles of rats. Daily intraperitoneal administration of huperzine A for 12 consecutive days produced significant reversals of the beta-amyloid-induced deficit in learning a water maze task. This treatment also reduced the loss of choline acetyltransferase activity in cerebral cortex, and the neuronal degeneration induced by beta-amyloid protein-(1-40). In addition, huperzine A partly reversed the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax and P53 proteins and reduced the apoptosis that normally followed beta-amyloid injection. The present findings confirm that huperzine A can alleviate the cognitive dysfunction induced by intracerebroventricular infusion of beta-amyloid protein-(1-40) in rats. The beneficial effects are not confined to the cholinergic system, but also include favorable changes in the expression of apoptosis-related proteins and in the extent of apoptosis in widespread regions of the brain.

Huperzine A improves cognitive deficits caused by chronic cerebral hypoperfusion in rats.

The effects of (-)-huperzine A, a promising therapeutic agent for Alzheimer's disease, on learning behavior and on alterations of the cholinergic system, the oxygen free radicals and energy metabolites induced by permanent bilateral ligation of the common carotid arteries were investigated in rats. Daily oral administration of huperzine A produced a significant improvement of the deficit in the learning of the water maze task, beginning 28 days after ischemia, correlating to about 33-40% inhibition of acetylcholinesterase activity in cortex and hippocampus. Huperzine A significantly restored the decrease in choline acetyltransferase activity in hippocampus and significantly reduced the increases in superoxide dismutase, lipid peroxide, lactate and glucose to their normal levels. The present findings demonstrate that the improvement by huperzine A of the cognitive dysfunction in the late phase in chronically hypoperfused rats is due to its effects, not only on the cholinergic system, but also on the oxygen free radical system and energy metabolism. Our results strongly suggest that huperzine A has therapeutic potential for the treatment of dementia caused by cholinergic dysfunction and/or decrease of cerebral blood flow.

Effect of huperzine A on working memory in reserpine- or yohimbine-treated monkeys.

The effect of huperzine A, a reversible and selective acetylcholinesterase inhibitor, on reserpine- or yohimbine-induced spatial working memory deficits in monkeys has been examined using the delayed response task that depends on the integrity of prefrontal cortex. Reserpine (0.1 mg/kg, i.m.) or yohimbine (0.01 mg/kg, i.m.) led to significant impairments in the monkeys' ability to perform the delayed response task. Huperzine A (0.01 mg/kg, i.m. in reserpine-treated monkeys; 0.01-0.1 mg/kg, i.m. in yohimbine-treated monkeys) significantly improved the reserpine- or yohimbine-induced memory impairments. The effect of huperzine A on memory impairments exhibited an inverted U-shaped dose-response pattern. Our data suggest that huperzine A may improve working memory via an adrenergic mechanism.