Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording; this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.
Animals ; CA1 Region, Hippocampal/physiology* ; Male ; Association Learning/physiology* ; Neuronal Plasticity/physiology* ; Cues ; Memory/physiology* ; Synapses/physiology* ; Conditioning, Classical/physiology* ; Excitatory Postsynaptic Potentials/physiology* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Rats ; Optogenetics

(±)-Penicithrones A-D (1a/1b-4a/4b), four novel pairs of anthrone-cyclopentenone heterodimers characterized by a distinctive bridged 6/6/6-5 tetracyclic core skeleton, together with three previously identified compounds (5-7), were isolated from the crude extract of the mangrove-derived fungus Penicillium sp., guided by heteronuclear single quantum correlation (HSQC)-based small molecule accurate recognition technology (SMART 2.0) and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based molecular networking. The structural elucidation of new compounds was accomplished through comprehensive spectroscopic analysis, and their absolute configurations were determined using DP4+ ¹³C nuclear magnetic resonance (NMR) calculations and electronic circular dichroism (ECD) calculations. Compounds 1a/1b-4a/4b demonstrated moderate cytotoxicity against three human cancer cell lines HeLa, HCT116 and MCF-7 with half maximal inhibitory concentration (IC₅₀) values ranging from 15.95 ± 1.64 to 28.56 ± 2.59 μmol·L^-1.
Humans ; Penicillium/chemistry* ; Molecular Structure ; Cyclopentanes/isolation & purification* ; Cell Line, Tumor ; Antineoplastic Agents/pharmacology* ; Tandem Mass Spectrometry ; Dimerization ; HeLa Cells ; Magnetic Resonance Spectroscopy

Objective To observe the clinical effect of Xiaotan Zhitong gel on heel pain caused by plantar fasciitis.Methods A total of 72 patients diagnosed with plantar fasciitis heel pain were randomly divided into observation group(36 cases)and control group(36 cases).Patients in the control group were treated with local application of diclofenac diethylamine emulgel twice a day and those in the treatment group were treated with Xiaotan Zhitong gel twice a day,with both treatments lasting for 28 d.The visual analogue scale(VAS)score of heel pain,the quantitative scale score of heel pain symptom grading,and the American Foot and Ankle Society(AOFAS)ankle-hindfoot score were evaluated before and after treatment.The changes of plantar fascia thickness were examined ultrasonographically before and after treatment in the 2 groups.The effective rates of treatment and the 3-month relapse rates were observed in the 2 groups.Results Before treatment,there were no significant differences in heel pain VAS score,heel pain symptom grading quantitative scale score,AOFAS ankle-hindfoot score,or plantar fascia thickness between the 2 groups(all P＞0.05).After treatment,the above indexes were improved in both groups compared with those before treatment(all P＜0.05);and the pain VAS score,heel pain symptom grading quantitative scale total score,heel pain symptom grading quantitative scale pain score,heel pain symptom grading quantitative scale pressure score,heel pain symptom grading quantitative scale dysfunction score,and AOFAS ankle-hindfoot score in the observation group were significantly improved compared with those in the control group(all P＜0.05).The thickness of plantar fascia was significantly thinner than that of the control group(P＜0.05),and the insomnia scores on the heel pain symptom grading quantitative scale were not significantly different between the 2 groups(P＞0.05).The effective rate of the observation group(80.6%,29/36)was significantly higher than that of the control group(55.6%,20/36)(P＜0.05),and the 3-month recurrence rate in the observation group(16.7%,6/36)was significantly lower than that of the control group(41.7%,15/36)(P＜0.05).Conclusion Xiaotan Zhitong gel can reduce heel pain,improve foot function,and reduce plantar fascia thickness in patients with plantar fasciitis,also with low recurrence rate after treatment.

Programmed cell death protein ligand-1(PD-L1)is an important immune checkpoint molecule that plays an important role in regulating the body's immune response.Several clinical studies have shown that the expression level of PD-L1 in tumors is closely related to the efficacy of immune checkpoint inhibitors.Due to the spatial and temporal heterogeneity of tumors,immunohistochemical methods commonly used in clinical practice cannot accurately and comprehensively reflect the ex-pression level of PD-L1 in patients.Given that nuclear-medicine molecular imaging technology can noninvasively,real-time,dy-namically and visually monitor the expression level of PD-L1 in vivo at the molecular level,this article mainly focuses on the re-search of peptide-based radiolabeled molecular probes targeting PD-L1,with the aim of providing guidance for the search of no-vel peptide molecular probes for immunoimaging as well as for the screening of immunotherapy-suitable patients and evaluation of therapeutic efficacy,and other clinical applications.

Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,68Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95％and radiochemical purity of 97％.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NC1-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.

Objective:To investigate the characteristics of enterovirus (EV) VP1 gene from cases with hand, foot and mouth disease (HFMD) in Songjiang district of Shanghai in 2019.Methods:Samples from suspected HFMD cases were detected using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Human rhabdomyosarcoma (RD) cells were used for EV culture. VP1 genes of the isolated EV A species were sequenced. The sequences of nucleotide and amino acid of EV A species were used in phylogenetic and homology analysis by MEGA X software.Results:Totally 207 HFMD specimens were detected in 2019, of which 188 specimens were screened positive for EV. The positive rates of Coxsackievirus (CV)-A6, CV-A16, CV-A10 and CV-A4 were 47.34% (89/188), 41.49% (78/188), 3.72% (7/188) and 2.66% (5/188), respectively. Other EV species were 4.79% (9/188) positive and EV-A71 was not detected. During the summer epidemic peak of HFMD (May to July), B1 gene subtype of CV-A16 was detected more frequently, of which B1a and B1b evolutionary branches were prevalent together. The CV-A6 virus of D3a branch dominated in secondary peak of autumn and winter (September to December). CV-A10 and CV-A4 were sporadic and both respective strains belonged to subtypes of C2 gene. Compared with the prototype strains, the nucleotide (amino acid) sequence homologies of CV-A6, CV-A16, CV-A10 and CV-A4 VP1 genes were 79.22%-81.78% (95.97%~-97.19%), 62.70%-65.54% (90.10%-91.30%), 81.76%-82.65% (91.63% -92.03%) and 81.09%-81.79% (97.27%-97.67%), respectively.Conclusions:The diversity and complexity of HFMD pathogen epidemic increase the difficulty of HFMD prevention and control. The expansion of EV surveillance programs and the studies on the molecular epidemiology of EV are helpful for the prevention and control of HFMD.

Objective:To provide epidemiological data and clinical evidence for cosmetic adverse reactions.Methods:A retrospective clinical analysis was carried out on a total 820 outpatients (23 males and 797 females) suspected to be with cosmetic adverse reactions from January 2014 - October 2017, and average age of these patients was 7~75 (32.66±8.09) years. Suspicious cosmetics patch tests were performed in some patients. Suspicious cosmetics patch tests were performed in 687 patients.Results:Among 820 patients with cosmetic adverse reactions, women accounted for 97.20% and men accounted for 2.80%. Age distribution was most common among young people aged 21-40 years, accounting for 71.34%. The highest level of education was higher education, accounting for 59.69%. Occupational distribution was most commonly concentrated in employees and unemployed persons, accounting for 28.54% and 18.66%, respectively. A history of cosmetics allergies accounted for 17.28%. Cosmetic contact dermatitis was the most common clinical type of cosmetic adverse reactions, accounting for 92.70%. A total of 1682 suspected pathogenic cosmetics were involved. The positive rate of the cosmetic original patch test was 42.39%. Among the cosmetics with a positive patch test, moisturizing, anti-wrinkle and whitening freckle cosmetics accounted for the highest proportion, 31.59%, 15.09%, and 12.68%, respectively.Conclusions:Cosmetic contact dermatitis is the most common type of cosmetic adverse reaction. Patch testing is helpful in identifying the contact allergens in cosmetic adverse reaction.

Objective: To explore the effect of enterostomy on analgesic pattern in advanced digestive tract cancer. Methods: A retrospective cohort study was carried out, which was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (E2018026). Inclusion criteria were as follows: (1)age and gender were not limited; (2) all the gastrointestinal malignancies were confirmed histologically, and local recurrence or metastasis were confirmed by CT or MR; (3) numerical rating scale (NRS) ≥4 points, opioid analgesic drugs were required; (4) informed consents were signed by patients of their own. Exclusion criteria were as follows: (1) malignancies of early stage; (2) suspicious adverse mental states which might lead to poor administration compliance; (3) hypersensitivity or allergic reactions to opioids. Clinical data of patients with advanced gastrointestinal cancer receiving comprehensive treatment at the Medical Oncology Department of the Sixth Affiliated Hospital of Sun Yat-sen University from September 2016 to April 2017 were retrospectively collected. The patients were divided into the stoma group and the non-stoma group. The clinical findings of two groups were analyzed, including age, sex, ostomy status, pain location, presence or absence of intestinal obstruction, pain characteristics, selection of opioid analgesic agents, treatment of side effects of analgesics. Pain was assessed using brief pain inventory(BPI) table and NRS score. Strong opioids were prescribed for patients of NRS ≥4. Patients who were intolerant to opioids required opioid titration. The titration drugs included oral or IV morphine and oxycodone. After achievement of adequate pain control, long-acting opioids were administered, which included sustained-release morphine tablets, controlled release oxycodone and transdermal fentanyl. Criteria for pain relief included NRS≤3, breakthrough pain <3 times/day and duration of adequate pain control >3 days. The χ² test and the Wilcoxon signed rank sum test (nonparametric test) were used to analyze the clinical features of patients in the stoma and non-stomach groups. In order to find the factors associated with maintenance therapy and the use of laxatives, the variables were compared as well as in multivariate analysis with multiple regression models. For all the statistical tests, a value of P<0.05 in a two-tailed test was established as the alpha significance level. Result: A total of 123 patients were enrolled in this study, including 79 males (64.2%) and 44 females (35.8%) with a median age of 51 years. Fifty-two patients were in stoma group, including 30 (24.4%) of ileostomy and 22 (17.9%) of colostomy, and 71 patients were in non-stoma group. Pain of 40 (76.9%) patients in stoma group located in abdomenopelvic site while the pain of 44 (62.0%) patients in non-stoma group located in other sites. Compared with non-stoma group, cases in stoma group complained more abdominopelvic pain (73% vs. 62.0%, P<0.001).The median NRS pain score before treatment in the stoma group and the non-stoma group was 5.7 and 5.6, respectively, without statistically significant difference (P=0.741). After analgesic management, the above scores reduced to 2.1 and 2.3, respectively, without statistically significant difference as well (P=0.092). Analgesic treatment was effective in 111 cases (90.2%), including 49 cases (94.2%) in the stoma group, and 62 cases (87.3%) in the non-stoma group, and there was no statistically significant difference between the two groups (P=0.202). There was more application of fentanyl transdermal patch [34.6%(18/52) vs. 9.8%(7/71)] in the stoma group, while more application of lactulose laxative [78.9%(56/71) vs. 61.5%(32/52)](χ²=10.023, P=0.002) in the non-stoma group. Multivariate analysis revealed that ostomy (OR=0.290, 95%CI: 0.102-0.824, P=0.009) and pain site (OR=5.691, 95%CI:1.709-18.948, P=0.005) were independent factors affecting the choice of the first line opioid sustained release agent. Of the 123 patients with maintaining analgesia, 98 had available data of laxative use, of whom 46 used laxatives to prevent or treat constipation, and the proportion of laxatives in stoma group (21.2%, 11/52) was significantly lower than that in non-stoma group (49.3%, 35/71) (χ²=6.957, P=0.008). Multivariate analysis of the application of laxative use showed that age (OR=0.281, 95% CI: 0.123-0.684, P=0.010) and ostomy (OR=2.621, 95% CI: 1.033-6.687, P=0.045) were independent factors affecting the use of lactulose laxatives. Conclusions Enterostomy may affect the analgesic pattern in advanced digestive tract cancer. Patients with stoma are more likely to use fentanyl transdermal patches and younger patients with stoma do not need prophylactic use of laxatives.

[Abstrect] Objective To explore the effect of enterostomy on analgesic pattern in advanced digestive tract cancer. Methods A retrospective cohort study was carried out, which was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat?sen University (E2018026). Inclusion criteria were as follows: (1)age and gender were not limited; (2) all the gastrointestinal malignancies were confirmed histologically, and local recurrence or metastasis were confirmed by CT or MR; (3) numerical rating scale (NRS) ≥4 points, opioid analgesic drugs were required; (4) informed consents were signed by patients of their own. Exclusion criteria were as follows: (1) malignancies of early stage; (2) suspicious adverse mental states which might lead to poor administration compliance; (3) hypersensitivity or allergic reactions to opioids. Clinical data of patients with advanced gastrointestinal cancer receiving comprehensive treatment at the Medical Oncology Department of the Sixth Affiliated Hospital of Sun Yat?sen University from September 2016 to April 2017 were retrospectively collected. The patients were divided into the stoma group and the non?stoma group. The clinical findings of two groups were analyzed, including age, sex, ostomy status, pain location, presence or absence of intestinal obstruction, pain characteristics, selection of opioid analgesic agents, treatment of side effects of analgesics. Pain was assessed using brief pain inventory (BPI) table and NRS score. Strong opioids were prescribed for patients of NRS ≥4. Patients who were intolerant to opioids required opioid titration. The titration drugs included oral or IV morphine and oxycodone. After achievement of adequate pain control, long?acting opioids were administered, which included sustained?release morphine tablets, controlled release oxycodone and transdermal fentanyl. Criteria for pain relief included NRS≤3, breakthrough pain <3 times/day and duration of adequate pain control >3 days. The χ2 test and the Wilcoxon signed rank sum test (nonparametric test) were used to analyze the clinical features of patients in the stoma and non?stomach groups. In order to find the factors associated with maintenance therapy and the use of laxatives, the variables were compared as well as in multivariate analysis with multiple regression models. For all the statistical tests, a value of P<0.05 in a two?tailed test was established as the alpha significance level. Result A total of 123 patients were enrolled in this study, including 79 males (64.2%) and 44 females (35.8%) with a median age of 51 years. Fifty?two patients were in stoma group, including 30 (24.4%) of ileostomy and 22 (17.9%) of colostomy, and 71 patients were in non?stoma group. Pain of 40 (76.9%) patients in stoma group located in abdomenopelvic site while the pain of 44 (62.0%) patients in non?stoma group located in other sites. Compared with non?stoma group, cases in stoma group complained more abdominopelvic pain (73% vs. 62.0%, P<0.001).The median NRS pain score before treatment in the stoma group and the non?stoma group was 5.7 and 5.6, respectively, without statistically significant difference (P=0.741). After analgesic management, the above scores reduced to 2.1 and 2.3, respectively, without statistically significant difference as well (P=0.092). Analgesic treatment was effective in 111 cases (90.2%), including 49 cases (94.2%) in the stoma group, and 62 cases (87.3%) in the non?stoma group, and there was no statistically significant difference between the two groups (P=0.202). There was more application of fentanyl transdermal patch [34.6%(18/52) vs. 9.8%(7/71)] in the stoma group, while more application of lactulose laxative [78.9%(56/71) vs. 61.5%(32/52)]( χ2=10.023, P=0.002) in the non?stoma group. Multivariate analysis revealed that ostomy (OR=0.290, 95%CI:0.102?0.824, P=0.009) and pain site (OR=5.691, 95%CI:1.709?18.948, P=0.005) were independent factors affecting the choice of the first line opioid sustained release agent. Of the 123 patients with maintaining analgesia, 98 had available data of laxative use, of whom 46 used laxatives to prevent or treat constipation, and the proportion of laxatives in stoma group (21.2%, 11/52) was significantly lower than that in non?stoma group (49.3%, 35/71) (χ2=6.957, P=0.008). Multivariate analysis of the application of laxative use showed that age (OR=0.281, 95% CI: 0.123?0.684, P=0.010) and ostomy (OR=2.621, 95% CI: 1.033?6.687, P=0.045) were independent factors affecting the use of lactulose laxatives. Conclusions Enterostomy may affect the analgesic pattern in advanced digestive tract cancer. Patients with stoma are more likely to use fentanyl transdermal patches and younger patients with stoma do not need prophylactic use of laxatives.

[Abstrect] Objective To explore the effect of enterostomy on analgesic pattern in advanced digestive tract cancer. Methods A retrospective cohort study was carried out, which was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat?sen University (E2018026). Inclusion criteria were as follows: (1)age and gender were not limited; (2) all the gastrointestinal malignancies were confirmed histologically, and local recurrence or metastasis were confirmed by CT or MR; (3) numerical rating scale (NRS) ≥4 points, opioid analgesic drugs were required; (4) informed consents were signed by patients of their own. Exclusion criteria were as follows: (1) malignancies of early stage; (2) suspicious adverse mental states which might lead to poor administration compliance; (3) hypersensitivity or allergic reactions to opioids. Clinical data of patients with advanced gastrointestinal cancer receiving comprehensive treatment at the Medical Oncology Department of the Sixth Affiliated Hospital of Sun Yat?sen University from September 2016 to April 2017 were retrospectively collected. The patients were divided into the stoma group and the non?stoma group. The clinical findings of two groups were analyzed, including age, sex, ostomy status, pain location, presence or absence of intestinal obstruction, pain characteristics, selection of opioid analgesic agents, treatment of side effects of analgesics. Pain was assessed using brief pain inventory (BPI) table and NRS score. Strong opioids were prescribed for patients of NRS ≥4. Patients who were intolerant to opioids required opioid titration. The titration drugs included oral or IV morphine and oxycodone. After achievement of adequate pain control, long?acting opioids were administered, which included sustained?release morphine tablets, controlled release oxycodone and transdermal fentanyl. Criteria for pain relief included NRS≤3, breakthrough pain <3 times/day and duration of adequate pain control >3 days. The χ2 test and the Wilcoxon signed rank sum test (nonparametric test) were used to analyze the clinical features of patients in the stoma and non?stomach groups. In order to find the factors associated with maintenance therapy and the use of laxatives, the variables were compared as well as in multivariate analysis with multiple regression models. For all the statistical tests, a value of P<0.05 in a two?tailed test was established as the alpha significance level. Result A total of 123 patients were enrolled in this study, including 79 males (64.2%) and 44 females (35.8%) with a median age of 51 years. Fifty?two patients were in stoma group, including 30 (24.4%) of ileostomy and 22 (17.9%) of colostomy, and 71 patients were in non?stoma group. Pain of 40 (76.9%) patients in stoma group located in abdomenopelvic site while the pain of 44 (62.0%) patients in non?stoma group located in other sites. Compared with non?stoma group, cases in stoma group complained more abdominopelvic pain (73% vs. 62.0%, P<0.001).The median NRS pain score before treatment in the stoma group and the non?stoma group was 5.7 and 5.6, respectively, without statistically significant difference (P=0.741). After analgesic management, the above scores reduced to 2.1 and 2.3, respectively, without statistically significant difference as well (P=0.092). Analgesic treatment was effective in 111 cases (90.2%), including 49 cases (94.2%) in the stoma group, and 62 cases (87.3%) in the non?stoma group, and there was no statistically significant difference between the two groups (P=0.202). There was more application of fentanyl transdermal patch [34.6%(18/52) vs. 9.8%(7/71)] in the stoma group, while more application of lactulose laxative [78.9%(56/71) vs. 61.5%(32/52)]( χ2=10.023, P=0.002) in the non?stoma group. Multivariate analysis revealed that ostomy (OR=0.290, 95%CI:0.102?0.824, P=0.009) and pain site (OR=5.691, 95%CI:1.709?18.948, P=0.005) were independent factors affecting the choice of the first line opioid sustained release agent. Of the 123 patients with maintaining analgesia, 98 had available data of laxative use, of whom 46 used laxatives to prevent or treat constipation, and the proportion of laxatives in stoma group (21.2%, 11/52) was significantly lower than that in non?stoma group (49.3%, 35/71) (χ2=6.957, P=0.008). Multivariate analysis of the application of laxative use showed that age (OR=0.281, 95% CI: 0.123?0.684, P=0.010) and ostomy (OR=2.621, 95% CI: 1.033?6.687, P=0.045) were independent factors affecting the use of lactulose laxatives. Conclusions Enterostomy may affect the analgesic pattern in advanced digestive tract cancer. Patients with stoma are more likely to use fentanyl transdermal patches and younger patients with stoma do not need prophylactic use of laxatives.