Distinct Thalamo-Subcortical Circuits Underlie Painful Behavior and Depression-Like Behavior Following Nerve Injury.

Clinically, chronic pain and depression often coexist in multiple diseases and reciprocally reinforce each other, which greatly escalates the difficulty of treatment. The neural circuit mechanism underlying the chronic pain/depression comorbidity remains unclear. The present study reports that two distinct subregions in the paraventricular thalamus (PVT) play different roles in this pathological process. In the first subregion PVT posterior (PVP), glutamatergic neurons (PVPGlu) send signals to GABAergic neurons (VLPAGGABA) in the ventrolateral periaqueductal gray (VLPAG), which mediates painful behavior in comorbidity. Meanwhile, in another subregion PVT anterior (PVA), glutamatergic neurons (PVAGlu) send signals to the nucleus accumbens D1-positive neurons and D2-positive neurons (NAcD1→D2), which is involved in depression-like behavior in comorbidity. This study demonstrates that the distinct thalamo-subcortical circuits PVPGlu→VLPAGGABA and PVAGlu→NAcD1→D2 mediated painful behavior and depression-like behavior following spared nerve injury (SNI), respectively, which provides the circuit-based potential targets for preventing and treating comorbidity.

Medical students' perceptions and performance in an online regional anatomy course during the Covid-19 pandemic.

The present study evaluated the students' psychological well-being, experiences, performance, and perception of learning regional anatomy remotely. A regional anatomy remote learning curriculum was designed and learning materials were delivered virtually to 120 undergraduate medical students at Jinan University, China. All the students consented and voluntarily participated in this study by completing self-administered online questionnaires including the Zung's Self-Rating Anxiety and Depression Scales at the beginning and end of the learning session. A subset participated in focus group discussions. Most of the students (90.0%) positively evaluated the current distance learning model. More than 80% were satisfied with the content arrangement and coverage. Many students preferred virtual lectures (68.2%) and videos showing dissections (70.6%) during the distance learning sessions. However, writing laboratory reports and case-based learning were the least preferred modes of learning as they were only preferred by 23.2% and 14.1% of the students, respectively. There was no significant lockdown-related anxiety or depression reported by students using depression and anxiety scales as well as feedback from focus group discussions. The surveyed students' confidence scores in distance learning were significantly higher after 5 weeks than at the beginning of the session (3.05 ± 0.83 vs. 3.70 ± 0.71, P < 0.05). Furthermore, the present results showed no significant differences between the current group's academic performance in the unit tests as well as the final overall evaluation for different parts of the course compared to that of the previous year's cohort. The findings above were congruent with focus group discussion data that the use of the online teaching platform for regional anatomy significantly improved the students' confidence in virtual and self-directed learning and did not negatively affect their academic performance.

Comparison of the median effective concentration (EC50) and effect of sevoflurane with or without remifentanil in cesarean section with supreme laryngeal mask under narcotrend monitoring: a randomized trial.

BACKGROUND: Remifentanil combined with sevoflurane is a standard protocol for obstetric general anesthesia (GA). METHODS: In this study, we performed a randomized clinical trial to evaluate whether remifentanil has an effect on the median effective concentration (EC50) of sevoflurane and compare anesthetic outcomes of them in cesarean section with Supreme™ laryngeal mask airway (SLMA) under narcotrend monitoring. Ninety parturients with singleton births undergoing elective cesarean delivery (CD) with initial inhaled 1.0 minimum alveolar concentration (MAC) sevoflurane for anesthesia maintenance were assigned to three groups randomly and evenly: Group A (0.05 µg·kg-1·min-1 remifentanil combined with sevoflurane), Group B (0.1 µg·kg-1·min-1 remifentanil combined with sevoflurane), and Group C (normal saline combined with sevoflurane). Narcotrend was used to monitor the depth of anesthesia during the operation, with the level of anesthesia depth controlled within the D-E stage. The EC50 of sevoflurane was determined by Dixon's sequential method. The Narcotrend index, amount of bleeding, neonatal Apgar score, and corresponding treatment measures in the three groups were recorded. RESULTS: The results showed that the estimated EC50 of sevoflurane for obstetric GA was 0.80 MAC (95% CI: 0.63-0.95 MAC) in group A, 0.82 MAC (95% CI: 0.63-0.96 MAC) in group B, and 0.80 MAC (95% CI: 0.63-0.95 MAC) in group C. There was no statistically significant difference in the estimated EC50 of sevoflurane, time to wakefulness, Apgar score, amount of intraoperative bleeding, and postoperative bleeding within 24 hours between the three groups (all P>0.05). CONCLUSIONS: The addition of remifentanil at 0.05-0.1 µg·kg-1·min-1 did not change the EC50 of sevoflurane and anesthetic quality. The concentration of inhaled anesthetics can be minimized with Narcotrend monitoring. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000034512.

SUMOylation of spastin promotes the internalization of GluA1 and regulates dendritic spine morphology by targeting microtubule dynamics.

Dendritic spines are specialized structures involved in neuronal processes on which excitatory synaptic contact occurs. The microtubule cytoskeleton is vital for maintaining spine morphology and mature synapses. Spastin is related to microtubule-severing proteases and is involved in synaptic bouton formation. However, it is not yet known if spastin can be modified by Small Ubiquitin-like Modifier (SUMO) or how this modification regulates dendritic spines. Spastin was shown to be SUMOylated at K427, and its deSUMOylation promoted microtubule stability. In addition, SUMOylation of spastin was shown to affect signalling pathways associated with long term synaptic depression. SUMOylated spastin promoted the development of dendrites and dendritic spines. Moreover, SUMOylated spastin regulated endocytosis and affected the transport of the AMPA receptor, GluA1. Our findings suggest that SUMOylation of spastin promotes GluA1 internalization and regulates dendritic spine morphology through targeting of microtubule dynamics.

Supplementary Regional Anatomy Teaching by Surgeons Enhances Medical Students Mastery of Anatomical Knowledge and Positively Impacts Their Choice of Future Career.

BACKGROUND: Anatomy is fundamental to the practice of medicine and surgery. Anatomy is also increasingly being taught by basic medical scientists or postclinical practice surgeons, thereby potentially detaching it from ongoing clinical realities. OBJECTIVE: To evaluate whether supplementing regional anatomy teaching using surgeons enhances medical students' mastery of anatomical knowledge and how it impacts their choice of a future career. DESIGN: This was a descriptive study. SETTING: An integrated tuition model in which basic regional anatomy was supplemented with clinical correlates taught by surgeons was devised and implemented at Jinan University Medical School. PARTICIPANTS: Soon after the third-year medical students finished dissecting each region (e.g., head and neck, limbs, etc.) of the human body, the surgeons from relevant specialties and sub-specialties were invited to give clinical application lectures. A self-administered questionnaire was used to evaluate all the students' perceptions of the integrated teaching model, perceived mastery of anatomical knowledge and determinants of future career choice. RESULTS: More than half of the students believe that regional anatomy is more closely related to surgery than systemic anatomy. Over 70% of the students have a positive attitude towards this teaching model where surgeons supplement regional anatomy with clinical correlates, and 98% of the students are in favor of integrating human body structural knowledge into clinical problems to learn anatomy. In addition, 78% of the students believe that the surgeons' participation in the teaching of regional anatomy helps them better understand human body structures and their clinical significance. However, some of their responses point towards the clinical correlate disconnection from the basic anatomy content. Furthermore, the majority of the students plan to become clinical doctors. After studying regional anatomy, the proportion of students who elected to be surgeons decreased slightly. However, the number of students who affirmatively planned to become surgeons in the future increased slightly, and 90% of these students were able to specify a chosen and preferred subspecialty of surgery. CONCLUSIONS: Surgeons' involvement in regional anatomy is of major benefit to students in understanding the human anatomy and its clinical significance, as well as positively impact on the decision to pursue a career in surgery.

A convolutional neural network-based linguistic steganalysis for synonym substitution steganography.

In this paper, a linguistic steganalysis method based on two-level cascaded convolutional neural networks (CNNs) is proposed to improve the system's ability to detect stego texts, which are generated via synonym substitutions. The first-level network, sentence-level CNN, consists of one convolutional layer with multiple convolutional kernels in different window sizes, one pooling layer to deal with variable sentence lengths, and one fully connected layer with dropout as well as a softmax output, such that two final steganographic features are obtained for each sentence. The unmodified and modified sentences, along with their words, are represented in the form of pre-trained dense word embeddings, which serve as the input of the network. Sentence-level CNN provides the representation of a sentence, and can thus be utilized to predict whether a sentence is unmodified or has been modified by synonym substitutions. In the second level, a text-level CNN exploits the predicted representations of sentences obtained from the sentence-level CNN to determine whether the detected text is a stego text or cover text. Experimental results indicate that the proposed sentence-level CNN can effectively extract sentence features for sentence-level steganalysis tasks and reaches an average accuracy of 82.245%. Moreover, the proposed steganalysis method achieves greatly improved detection performance when distinguishing stego texts from cover texts.

Effect of methylprednisolone on the activities of caspase-3, -6, -8 and -9 in rabbits with acute spinal cord injury.

The present study aimed to investigate the effect of methylprednisolone (MP) on the activities of caspase-3, -6, -8 and -9 in rabbits with acute spinal cord injury (ASCI) and to explore the mechanism underlying the antiapoptotic effect of MP on ASCI. Modified Allen's method was employed to establish the ASCI animal model. The animals were randomly divided into a sham (S; n=12), ASCI (C; n=36) and MP group (T; n=36). At 8, 24 and 72 h and 7, 14 and 28 days after ASCI, the animals were sacrificed and the spinal cord was collected. The absorbance (A) was measured with a microplate reader and the activities of caspase-3, -6, -8 and -9 were calculated followed by comparisons among the groups. In the S group, the activities of the four caspases were low. In the C and T groups, the caspase activities increased at 8 h after injury, peaked at 24 h and remained at a high level 3 days after injury. However, the caspase activities began to decrease at 7 days after injury and were significantly reduced at 14 and 28 days after ASCI. Furthermore, the caspase activities in the T group were markedly lower than those in the C group at 8 and 24 h and 3 and 7 days after surgery (P<0.05), but significant differences were not observed at 14 and 28 days after injury (P>0.05). In conclusion, MP exerted an antiapoptotic effect via inhibition of the activities of caspase-3, -6, -8 and -9 in an animal model of ASCI.

[A clinical study of tension-free inguinal hernioplasty in patients with different ages].

OBJECTIVE: To study the application of mesh and hernia ring for tension-free hernia repair in inguinal hernioplasty in patients with different ages. METHODS: A total of 190 patients with inguinal hernia undergoing tension-free hernia repair were divided into two groups with age above and below 60 years, and the surgical effect and complications were compared. RESULTS: Tension-free hernia repair with mesh and hernia ring was superior to conventional hernia repair in terms of operative time, mean time for exercise and pain in patients above 60 years, but not in patients below 60 years. CONCLUSION: Surgical repair of inguinal hernia should be performed with individualized surgical plans.

[Studies on antiproliferative effect of flavones compounds isolated from Yao herb medicines].

OBJECTIVE: To detect the cytotoxicity and in vitro antiproliferative effects of the flavones compounds isolated from some Yao herbal medicines, and analyze the basic structure-activity relationship. METHODS: The cytotoxicity on normal cells and antiproliferative effect on tumor cells were tested by MTT reduction assay respectively. RESULTS: Among the 6 flavones, the Eriodictyol-7-O-a-D-glucoside, Naringenin-7-O-beta-D-glucoside, quercetin and quercetin-3-O-beta-D-glucoside showed very low cytotoxicity to the two normal cells, Vero and MC cells, while the naringenin was high toxic to both of them. The eriodictyol was no toxic to Vero Cell but could affect MC cell at low concentration. The naringenin exhibited a wide-spectrum antiproliferative effect on all of the 7 tested cancer cell lines especially on the MCF-7 with low IC50 about 50 microg/ml. Among these cancer cells, the MCF-7 and HepG2 were more sensitive to the flavones compounds than the others. Both of them were inhibited by eriodictyol, quercetin and naringenin even at low test concentration. Furthermore, the antiproliferative effects of these compounds were concentration-related. CONCLUSION: Some of flavones compounds isolated from some Yao herb medicines showed high antiproliferative effect on cancer cells with low cytotoxicity on normal cells.

[Distribution of neuronal nitric oxide synthase-immunopositive neurons in rat corpus striatum and their ultrastructures].

OBJECTIVE: To observe the distribution of neuronal nitric oxide synthase (nNOS)-immunopositive neurons in rat corpus striatum and their ultrastructural features. METHODS: Brain tissue specimens were obtained from normal SD rats, in which nNOS-immunopositive neurons were visualized by ABC immunocytochemistry and observed under immunoelectron microscope with pre-embedding staining. RESULTS: Under light microscope, nNOS-immunopositive neurons appeared brown with distinct profiles of the cell body and processes. These neurons, mostly medium-sized and small cells, were located mainly in the lateral region of the corpus striatum. Only a few immunopositive neurons were detected in the medial region of the corpus striatum. Immunohistochemistry and transmission electron microscopy identified the nNOS-immunopositive neurons as interneurons possessing large nuclei with small amount of cytoplasma. The immunopositive granules were visualized as black plaques, and the larger ones distributed mainly in the cell bodies, some with monolayer membrane encapsulation. The small granules did not have the encapsulation, scattering in perinuclear regions and under the cell membrane, but not in the cell body. The immunopositive granules were also found in the axons and dendrites, but not in the vesicles of the synapses. In addition, many immunopositive terminals were found close to the blood vessels. CONCLUSIONS: nNOS-immunopositive neurons in rat corpus striatum are mainly medium-sized and small cells as is typical of the interneurons. The immunopositive granules locate in the cytoplasma, axons and dendrites, and larger granules have membrane coating while small ones do not, possibly in relation to their functions.

[Changes of neuronal nitric oxide synthase-immunopositive neurons in the central amygdaloid nucleus of spontaneously hypertensive rats].

OBJECTIVE: To observe the changes of neuronal nitric oxide synthase (nNOS)-immunopositive neurons in the central amygdaloid nucleus of spontaneously hypertensive rats (SHRs). METHODS: Thirty SHRs and 30 Wistar-Koyto rats (WKYs) were sacrificed at the ages of 90, 180, and 360 days respectively to observe the changes of nNOS-immunopositive neurons with ABC immunocytochemical assay. RESULTS: No significant changes were observed in the blood pressure of WKY rats at the specified time points, when SHRs maintained significantly higher blood pressures from 20.8+/-1.1 and 26.3+/-1.0 kPa (P<0.05), gradually increasing during the development of hypertension. The nNOS-immunopositive neurons in the central amygdaloid nucleus were of moderate sizes with long intersected nerve fibers. No significant changes were found in WKY rats. The number of the positive neurons decreased with age in SHRs, especially obvious at 360 days (P<0.05), which was significantly different from that in the WKYs (P<0.05). CONCLUSION: The reduction of nNOS-immunopositive neurons in the central amygdaloid nucleus of SHRs might accelerate the development of hypertension by modulating the cardiovascular function and sensory transmission.

Changes of neuronal nitric oxide synthase-immunoreactive neurons in the paraventricular hypothalamic nucleus of diabetic rats.

OBJECTIVE: To explore the role of nitric oxide in the development of diabetes mellitus by observing the changes of neuronal nitric oxide synthase (nNOS)-immunoreactive (nNOS-ir) neurons in the paraventricular hypothalamic nucleus (PVN) of diabetic rats. METHODS: Diabetic rat models were established by means of intraperitoneal streptozotocin injections. At the end of 2, 7 and 12 weeks after model establishment, tissue sampling was performed and the number of nNOS-ir neurons in PVN were counted and quantitatively analyzed. RESULTS: The number of nNOS-ir neurons in PVN of diabetic rats remained normal 2 weeks after model establishment (P >0.05) but was significantly increased by the time of 7 weeks (P <0.05); at the 12th weeks, the number of nNOS-ir neurons of diabetic group was still greater than that of the control group (P <0.05). CONCLUSION: The number of nNOS-ir neurons in PVN increases significantly in middle and advanced stages of diabetes, suggesting the possible relations between the nNOS activity changes in PVN and the changes in cerebral neuroendocrine and adrenal activity in diabetic condition.