Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca²⁺ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca²⁺ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca²⁺ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.
Mice ; Animals ; Primary Visual Cortex ; Extinction, Psychological/physiology* ; Learning/physiology* ; Fear/physiology* ; Hippocampus/physiology*

Objective:To investigate the correlation between pulmonary arteriovenous fistula (PAVF) and ischemic stroke, and to improve the diagnosis and treatment of embolic strokes of undetermined source.Methods:Five patients with ischemic stroke caused by PAVF admitted to Xiangya Hospital of Central South University from January 2017 to December 2020 were collected. The diagnosis, treatment and prognosis of stroke caused by PAVF were summarized based on literature review.Results:Among the 5 patients, 1 is male and 4 are females, with age of (34.4±9.3) years. Weakness of unilateral limb, slurred speech, vision changes, drooping eyelids, etc., were the first manifestations of stroke. The location of cerebral infarction was indefinite. In this study, 5 patients were all isolated PAVF, including 3 cases of left lower lung, 1 case of left upper lung and 1 case of right lower lung. All 5 patients underwent interventional therapy, were followed-up for 6 months and 12 months after surgery, and none of them had a new stroke attack, and only 1 case had recanalization of PAVF.Conclusions:PAVF is a rare vascular lesion, stroke caused by which is even rarer, with a lack of specificity in clinical manifestations. For young patients with unexplained embolic stroke, if the stroke has a sudden onset, the anterior and posterior circulation can be involved, and multiple vascular distribution regions are often involved, and it is difficult to find a clear emboli basis, with manifestations such as hypoxemia, PAVF should be considered. Percutaneous catheter intervention for PAVF is safe and effective, and is the preferred method for the treatment of PAVF.

Objective:To investigate the effects of airway humidification therapy on pertussis in infants.Methods:Sixty children with pertussis who received treatment in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2020 to September 2021 were included in this study. They were randomly divided into study and control groups, with 30 infants per group. The control group was treated with conventional drugs. The study group was subjected to airway humidification therapy based on conventional drug treatment. Clinical efficacy was evaluated in each group. Time to an improvement in clinical symptoms and length of hospital stay were recorded. Lung function indicators and serum inflammatory factor levels were determined before and after treatment. Pertussis-related complications were recorded.Results:The overall response rate in the study group was significantly higher than that in the control group (100.00% vs. 76.7%, χ2 = 5.82, P = 0.016). Time to disappearance of spastic cough, time to resolution of cyanosis, time to disappearance of pulmonary rales, and length of hospital stay in the study group were (3.10 ± 0.67) days, (1.53 ± 0.68) days, (4.27 ± 0.58) days, and (11.57 ± 0.73) days, respectively, which were significantly shorter than (4.23 ± 1.99) days, (2.67 ± 1.77) days, (5.63 ± 2.38) days, (13.33 ± 2.40) days ( t = 2.93, 3.27, 3.04, 3.86; P = 0.005, 0.002, 0.003, P < 0.001). Respiratory rate in the study group was significantly lower than that in the control group [(21.83 ± 1.15) breaths/minute vs. (24.23 ± 3.12) breaths/minute, t = 3.94, P = 0.002]. Tidal volume/kg body weight, the ratio of time to peak expiratory flow to total expiratory time and the ratio of volume to peak expiratory flow to total expiratory volume in the study group were (10.70 ± 0.81) mL/kg, (41.60 ± 1.57)%, (42.89 ± 1.44)%, respectively, which were significantly higher than (9.78 ± 1.34) mL/kg, (39.18 ± 3.37)%, (40.20 ± 3.05)% in the control group ( t = 3.21, 3.56, 4.36; P < 0.001, P = 0.001, P < 0.001). Serum tumor necrosis alpha (TNF-α), interleukin-6 and interleukin-8 levels in the study group were (62.44 ± 2.96) ng/L, (46.59 ± 1.96) ng/L, (54.63 ± 3.27) ng/L, respectively, which were significantly lower than (79.86 ± 3.30) ng/L, (58.20 ± 2.10) ng/L, (63.31 ± 3.86) ng/L in the control group ( t =21.53, 22.13, 9.38, all P < 0.001). The overall incidence of pertussis in the study group was significantly lower than that in the control group (3.3% vs. 26.7%, χ2 = 4.71, P = 0.030). Conclusion:Airway humidification therapy can shorten the time to reduction of symptoms of spasmodic pertussis, improve clinical efficacy, strengthen pulmonary ventilation function, lower respiratory tract inflammatory responses and reduce the risk of pertussis-related complications.

Objective:To investigate the changes and clinical significance of white blood cell (WBC) count and polymorphonuclear cells (PMN) proportion of synovial fluid after primary total knee arthroplasty (TKA).Methods:A total of 59 patients (92 knees) who underwent TKA from April 2021 to July 2021 were included, including 13 males (20 knees) and 46 females (72 knees). The patients were with average age 65.17±7.49 years old (range 48-79) and with body mass index (BMI) 27.64±3.74 kg/m 2 (range 17-36 kg/m 2). There were 26 cases involved lateral knee and 33 cases bilateral knees. The left knee was involved in 46 knees, while other 46 were involved in right side. There were 54 patients diagnosed as osteoarthritis (84 knees) and 5 as rheumatoid arthritis (8 knees). None of the patients received antibiotics after hospitalization. Antibiotics were used prophylactically 30 min before surgery and after surgery. The synovial fluid WBC count and PMN proportion were detected during operation (It reflects the normal preoperative level) and on the 2nd, 5th and 35th day after operation. The changes of these indexes were analyzed. The unmixed synovial fluid was collected after the incision of the joint capsule during the operation. The outer upper edge of the patella was taken as the puncture point to extract the synovial fluid on the 2nd, 5th and 35th days after the operation. The final follow-up end point was a diagnosis of acute periprothetic joint infection (PJI) or 90 days of follow-up for patients without PJI. Results:After operation, the synovial fluid WBC count and PMN proportion showed a trend of increasing and then decreasing. The synovial fluid WBC count were 0.222(0.100, 0.567)×10 9/L, 20.011(14.573, 29.129)×10 9/L, 6.080(3.676, 8.797)×10 9/L, 0.533(0.394, 0.749)×10 9/L before surgery and at 2nd, 5th and 35th day after surgery respectively. The difference before and after operation was statistically significant (χ 2=247.343, P<0.001). The synovial fluid PMN proportion were 19.9%(15.0%, 30.0%), 96.0%(95.0%, 97.0%), 91.0%(89.0%, 93.0%) and 20.5%(15.6%, 26.9%) respectively and with significant difference (χ 2=242.521, P<0.001). Pairwise comparison of synovial fluid WBC count and PMN proportion before and on day 35 indicated no statistical significance ( P>0.05). However, the differences compared with that at other time points were statistically significant ( P<0.05). Conclusion:The synovial fluid WBC count and PMN proportion increased rapidly in the short term after TKA and then decreased to the preoperative level at varied rates. Referring to the Musculoskeletal Infection Society (MSIS) recommended threshold for diagnosing infection during the acute stress period (within 5 d postoperatively) can result in false positives. Recovery to preoperative levels at 35th days postoperatively can be used as a basis for ruling out early infection. Thus, early joint fluid PMN proportion may have more diagnostic value than WBC counts.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

Based on the latest results of international researches, combining with the experiences of our team in the simulation of acute dyspnea, Xiangya Hospital Central South University has summarized 7 characteristics, procedures and methods of debriefing, including that immediate feedback happens after simulation; feedback is provided by a trained instructor with clinical experience; feedback time is at least longer than the simulation time; various international methods of feedback can be used; the content of feedback is the learning objective; oral feedback is preferred; video can be used to review the details. The study aims to provide a theoretical basis for debriefing in domestic scenario stimulation teaching, and finally improve the effectiveness of the scenario stimulation teaching.

Baylisascaris schroederi,a roundworm(ascaridoid)parasite specific to the bamboo-feeding giant panda(Ailuropoda melanoleuca),represents a leading cause of mortality in wild giant panda populations.Here,we present a 293-megabase chromosome-level genome assembly of B.schroederi to infer its biology,including host adaptations.Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations,suggesting their potential for transmission and rapid adaptation to new hosts.Genomic and anatomical lines of evidence,including expansion and positive selection of genes related to the cuticle and basal metabolisms,indicate that B.schroederi undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut parasitism.Additionally,we characterized the secretome of B.schroederi and predicted potential drug and vaccine targets for new control strategies.Overall,this genome resource provides new insights into the host adaptation of B.schroederi to the giant panda as well as the host-shift events in ascaridoid parasite lineages.Our findings on the unique biology of B.schroederi will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism.

Diagnostics is one of the most important bridge courses for medical students from basic to clinical. Doctor-patient communication runs through the whole process of patient diagnosis and treatment. How to improve medical students' ability of doctor-patient communication? Our teaching team has carried out continuous reform and explored the scientific effective teaching mode. Recently, through the construction of "doctor-patient communication skills" quality online course, efforts have made to build an online and offline blended learning mode, which has gradually realize the integration with diagnostics teaching, and has achieved remarkable results. It also provides a scientific practical basis for the integration of doctor-patient communication and other clinical courses, which is worthy of promotion.

Objective:To compare the minimally invasive transforaminal lumbar interbody fusion (MTLIF) with open transforaminal lumbar interbody fusion (OTLIF) in treatment of lumbar degenerative disease.Methods:Clinical data of 63 patients with single segment lumbar degenerative disease treated in Department of Orthopedics of Beijing Hospital from November 2015 to September 2016 were retrospectively analyzed, among whom 30 cases received MTLIF and 33 cases received OTLIF. The operative time, intraoperative X-ray exposure times, intraoperative blood lose, postoperative drainage,perioperative fever, adjacent segment degeneration, loosening of internal fixation and cage collapse were observed in two groups 4 years after operation, and the visual analog scale (VAS) score of the lower back and the leg, the Oswestry disability index (ODI) score were compared between two groups.Results:The operation time [(191.6±50.5) min] and radiation exposure times [(15.5±6.4) times] in MTLIF group were significantly more than those in OTLIF group [(105.8±23.1) min, (7.2±1.4)times, t=17.210, t=10.850,all P<0.01]. The intraoperative blood loss [(150.4±70.4) ml], postoperative drainage [(90.4±30.7)ml], VAS score (2.4±0.7) and ODI score (24.5±3.7) 2 weeks after surgery in MTLIF group were significantly lower than those in OTLIF group [(250.7±43.9)ml,(216.3±67.8)ml,(4.5±1.6),(30.6±4.6), t=-12.830, t=-14.070, t=-6.890, t=-5.805,all P<0.01]. There were no significant differences in the incidence of fever [1 case(3.3%) vs. 4 cases(12.1%),χ2=-1.661, P=0.20], VAS score[(1.2±0.7) vs. (1.3±0.6), t=-0.628, P=0.53], ODI score[(14.2±2.7) vs. (14.7±2.5), t=-0.756, P=0.45], fusion rate of Bridwell grade Ⅰ [86.7%(26/30) vs. 84.8%(28/33),χ2=0.042, P=0.84] 1 year after surgery; and the adjacent segment degeneration [0 case(0) vs. 1 case(3.0%),χ2=0.924, P=0.34], internal fixation loosening [1 case(3.3%) vs. 1 case(3.0%),χ2=0.005, P= 0.95] and cage collapse 4 years after surgery [1 case(3.3%) vs. 1case(3.0%),χ2=0.005, P=0.95] between MTLIF group and OTLIF group. Conclusion:Compared with OTLIF, MTLIF has longer operation time and more radiation exposure, but it can achieve full decompression, the same fusion rate, less bleeding, less trauma, faster recovery, fewer complications and satisfactory long-term effect.

ObjectiveTo investigate the correlation between systemic immune-inflammation index (SII) and prognosis in patients with hepatic alveolar echinococcosis. MethodsA retrospective analysis was performed for the clinical data of 242 patients who were admitted to Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, from January 2015 to December 2018 and underwent surgery for hepatic alveolar echinococcosis, and SII was calculated. The chi-square test was used for comparison of categorical data between two groups, and a Spearman correlation analysis was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of SII; the Kaplan-Meier method was used to plot survival curves and analyze overall survival time in the two groups, and the log-rank test was used for comparison of survival rates between the two groups; univariate and multivariate Cox regression analyses were used to identify the influencing factors for the prognosis of patients with hepatic alveolar echinococcosis. ResultsThe Spearman correlation analysis showed that SII was positively correlated with the postoperative fatality rate of patients with hepatic alveolar echinococcosis (r=0.267, P＜0.001). The ROC curve showed that the optimal cut-off value of SII before surgery was 758.92, and based on this, 242 patients with hepatic alveolar echinococcosis were divided into low SII (SII ≤758.92) group with 126 patients and high SII (SII ＞758.92) group with 116 patients. The low SII group had 1-, 3-, and 5-year survival rates of 98.20%, 88.47%, and 6610%, respectively, and the high SII group had 1-, 3-, and 5-year survival rates of 90.80%, 53.05%, and 27.40%, respectively. The low SII group had a cumulative survival rate of ＞50% and a mean survival time of 55.584 months (95% confidence interval［CI］: 53550-57.617), while the high SII group had a cumulative survival rate of ＜50%, a mean survival time of 39.384 months (95% CI: 35.070-43.698), and a median survival time of 43 months (95% CI: 34.694-51.306). The low SII group had a significantly better survival rate than the high SII group, and there was a significant difference in overall survival rate between the two groups (χ2=46.979, P＜005). The univariate analysis showed that SII ＞758.92 (hazard ratio ［HR］=5.907, 95% CI: 3.386-10.306, P=0.001) was an influencing factor for the overall survival time of patients with hepatic alveolar echinococcosis, and the multivariate Cox regression analysis showed that preoperative peripheral blood SII (HR=3.507, 95% CI: 1.911-6.435, P=0.001) was an independent risk factor for the overall survival rate of patients with hepatic alveolar echinococcosis. ConclusionPreoperative SII level is clearly correlated with the prognosis of patients with hepatic alveolar echinococcosis and can thus be used as a clinical indicator to evaluate the prognosis of patients. The higher the peripheral blood SII before surgery, the worse the prognosis of patients.