Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Objective·To analyze the diversity and composition of the maternal gut microbiota and vaginal microbiota in late pregnancy,neonatal meconium microbiota and vernix caseosa microbiota,and analyze the similarities,differences and correlations.Methods·This is a prospective study.Maternal stool samples and vaginal swabs in late-pregnancy,and neonatal meconium samples were collected from 11 mother-infant pairs at Xinhua Hospital,Shanghai Jiao Tong University School of Medicine from August to November 2018;the vernix caseosa from three sites(forehead,axilla,and inguinal crease)and meconium samples were collected from 14 healthy newborns at International Peace Maternity and Child Health Hospital,Shanghai Jiao Tong University School of Medicine in December 2018.All births were vaginal deliveries.The 16S rRNA gene V3?V4 region sequencing was used.The diversity,composition and similarities/differences of the maternal gut microbiota,the vaginal microbiota,and the neonatal meconium microbiota from the 11 mother-infant pairs,as well as the neonatal vernix caseosa microbiota and the meconium microbiota from the 14 newborns were analyzed.Results·The number of operational taxonomic units(OTUs),ACE index,Chao1 index,and Shannon index of maternal gut microbiota were all higher than those of vaginal microbiota;the ACE indices and the Chao1 indices of the vernix caseosa microbiota at three sites were all higher than those of meconium microbiota(P<0.01).The β diversity varied among the maternal gut microbiota,vaginal microbiota,and neonatal meconium microbiota(P<0.01).The β diversity of neonatal vernix caseosa microbiota from three sites(forehead,axilla,and inguinal crease)was similar,but different from meconium microbiota(P<0.01).At the phylum level,the dominant bacteria were Firmicutes(52.76%)and Bacteroidetes(41.67%)in the maternal gut microbiota,Firmicutes(74.36%)and Actinobacteria(21.25%)in the maternal vaginal microbiota,and Firmicutes(84.22%)and Proteobacteria(8.80%)in the neonatal vernix caseosa microbiota.The dominant bacterium in the neonatal meconium was Proteobacteria in the two batches of samples(81.11%and 88.72%,respectively).At the genus level,the dominant bacteria were Bacteroides(35.42%)and Faecalibacterium(10.12%)in the maternal gut microbiota,Lactobacillus(69.10%)and Bifidobacterium(11.30%)in the vaginal microbiota,and Lactobacillus(79.81%)and Pseudomonas(3.23%)in the vernix caseosa microbiota.The dominant bacterium in the neonatal meconium was Escherichia in the two batches of samples(55.21%and 31.18%,respectively).Conclusion·The α diversity of maternal gut microbiota is higher than that of vaginal microbiota and neonatal meconium microbiota,and it is higher in neonatal vernix caseosa than that in meconium microbiota.The Firmicutes is the predominant phylum in the maternal late-pregnancy gut microbiota,vaginal microbiota,and neonatal vernix microbiota.Lactobacillus is the predominant genus in both maternal vaginal and neonatal vernix caseosa microbiota.Proteobacteria in phylum and Escherichia in genus are predominant in meconium microbiota.The microbiota composition is similar in vernix caseosa at different body sites,but there are differences between the vernix caseosa microbiota and meconium microbiota.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

Objective: To investigate the effect of nursing intervention on the incidence of agitation and negative emotion in patients undergoing general anesthesia recovery. Methods: Totally 120 patients with general anesthesia admitted to the Binzhou Central Hospital, Shandong Province from January 2017 to January 2019 were divided into the control group and the observation group by random digits table method with 60 cases each. Those in the control group was given routine nursing, the observation group was given integrated care. The incidence rate of agitation, conscious recovery time, the time of wake-up score≥4 and negative emotional changes in the two groups were compared. Results: The incidence of agitation in the observation group was 6.67% (4/60), which was lower than that in the control group (25.0%, 15/60). The difference was statistically significant (χ² value was 6.253, P<0.05). The conscious recovery time, the time of wake-up score≥4 was (1.05±0.39), (16.34±1.21) h, both were shorter than the control group (2.68±0.42), (23.12±1.03) h, the difference was statistically significant (t value was 22.029, 33.050, P<0.01). The Kessler10 score of the observation group was 30.24±3.64,which was lower than that in the control group 24.84±2.35. The difference was statistically significant (t value was 9.654, P<0.01). Conclusions The operation room nursing intervention for patients with general anesthesia recovery can reduce the occurrence of agitation and reduce the negative emotion of patients, and the application effect is remarkable.

Objective To construct lentivirus containing CXCR4 gene and transfect MCF-7 cells , and obtain CXCR4 high-expressing MCF-7 cells. Methods CXCR4 gene was amplified by RT-PCR to construct CXCR4/pSin-EF2, which was transfected into HEK293T cells with psPAX2 and pMD2G vector for lentivirus packing. Packaged lentivirus was used to transfect human breast cancer cells MCF-7, with empty lentivirus as control. CXCR4 mRNA and protein expression levels were detected by RT-PCR and Western blot before and after transfection. And flow cytometry was used to detecte cell surface CXCR4 expression. Results The recombinant plasmid CXCR4/pSin-EF2 was constructed successfully,identified by double digestion and sequencing, and transfected into HEK293T cells to obtain high-titer lentivirus. RT-PCR and Western blot confirmed that the expression of CXCR4 in MCF-7 cells increased significantly after CXCR4 lentivirus transfection. Flow cytometry results showed that the CXCR4 positive rate increased from 26.78% to 99.29%, while there is no significant difference in CXCR4 expression between vector-transfected MCF-7 cells and non-transfected MCF-7 cells. Conclusion CXCR4 lentivirus and the breast cancer cell line with high and stable expression of CXCR4 (MCF-7CXCR4) were successfully constructed.

Objective: To observe the clinical effect of electroacupuncture (EA) combined with tuina on acute lumbar sprain and lumbar muscle tone before and after treatment. ＜br> Methods: A total of 130 acute lumbar sprain cases were randomly allocated into an observation group and a control group, 65 in each group. Cases in the observation group were treated with EA combined with tuina, whereas cases in the control group were treated with Diclofenac Sodium Dual Release Enteric-coated capsules. The muscle tones in two groups were tested before and after treatment. ＜br> Results: The recovery rate and overall response rate in the observation group were 66.2% and 93.8% respectively, versus 56.9% and 87.7% in the control group, showing no between-group statistical significances (P>0.05). After treatment, the force-displacement area under curve (AUC) in both groups showed a significance difference (P＜0.05). ＜br> Conclusion: Both EA combined with tuina and aforementioned oral medication have remarkable effects for acute lumbar sprain, and the former can better improve the lumbar muscle tone in patients with acute lumbar sprain.

Objective: To observe the clinical effect of tuina in rehabilitation following total hip replacement. Methods: 60 cases were randomly allocated into a treatment group and control group, 30 cases in each group. Cases in the treatment were treated with combined mina and rehabilitation, while cases in the control group were treated with rehabilitation alone. All treatment retained for two weeks. The results were observed 7 d, 2 weeks and 6 weeks following the total hip replacement using Harris scale and Hamilton Anxiety Rating Scale (HAMA).Results: For Harris scale, there were significant intra-group differences in different time frames (P＜0.05); there were no statistical differences between the two groups 1 d, 7 d and 6 weeks following the total hip replacement (P＞0.05); and there were statistical differences between the two groups 2 weeks following the total hip replacement. For HAMA scale, there were significant intra-group differences in different time frames (P＜0.05); there were no significant differences between the two groups 1 d following the total hip replacement; and there were substantial differences between the two groups 7 d, 2 weeks and 6 weeks following the total hip replacement. Conclusion: In a given unit time, combined mina and rehabilitation is superior to rehabilitation alone in improving the patients' post-operative pain, articular range of motion and anxiety.

Objective: To observe the effect of acupuncture and Chinese mina manipulation therapy in treating knee osteoarthritis, and analyze the alteration of musculus quadriceps femoris strength.Methods: A total of 80 patients were randomly assigned to a treatment group receiving acupuncture combined Chinese tuina manipulation therapy (n=40) and a control group receiving Fenbid treatment (n=40), curative effective score, Lequene & Mery assessment tests, and isokinetic evaluation were recorded before and after the treatment course. Results: The total effective rate was 90.0 % in the treatment group and 87.5% in the control group, without a significant difference between the two groups. Lequene & Mery assessment tests had no significant change. Musculus quadriceps femoris isokinetic evaluation improved significantly after the treatment course in the two groups (P＜0.05), and there was a significant difference between the two groups (P＜0.05). Conclusion: Acupuncture combined with tuina manipulation therapy and Fenbid treatment both can reduce knee pain and joint disability in the short term, though no improvement was shown in the severity of the disease.Acupuncture combined with mina manipulation therapy is better than Fenbid in improving the strength, total work and explosive force of the musculus quadriceps femoris.