Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

Objective:To compare the safety and efficacy of the " step-up approach" versus the " step-jump approach" in treatment of infected pancreatic necrosis (IPN).Method:The clinical data of IPN patients who underwent step-up strategy or step-jump strategy treatment at the Department of Pancreatic and Biliary Surgery of the First Affiliated Hospital of Harbin Medical University from December 2018 to November 2022 were analyzed retrospectively. Propensity score matching (PSM) was done based on the nearest neighbor matching method (1: 1 ratio). After matching the baseline data (the caliper value was 0.01), a total of 62 patients with IPN were included, including 41 males and 21 females, aged (41.1±13.1) years old. Patients who were treated with the step-up strategy were included in the step-up group, while patients who were treated with the step-jump strategy were included in the step-jump group. There were 31 patients in each group after PSM, and the treatment effect of the two groups were compared.Results:Of the 62 patients with IPN, 43 received surgical intervention, and 19 were managed successfully using symptomatic anti-inflammatory treatment or percutaneous catheter drainage. The total hospitalization cost of patients in the step-jump group was significantly higher than that in the step-up group [122 000 (73 000, 179 000) yuan vs. 88 000 (46 000, 144 000) yuan, P=0.034]. The overall cure rate of IPN patients in the step-jump group was 93.5%(29/31). The 2 patients who died had type Ⅲ IPN. In the IPN patients in the step-up group were all cured, and the overall cure rate was 100%(31/31), with no death. There were no statistical differences between the two groups in the rates of death, postoperative complications, residual infection, debridement ≥2 times, and positive bacterial culture in blood or drainage fluid (all P>0.05). A total of 19.4% (12/62) patients had postoperative complications, including 4 patients with abdominal bleeding, 3 patients with new organ dysfunction, 2 patients with gastrointestinal bleeding, 2 patients with gastrointestinal fistula, and 1 patient with venous thrombosis in both lower limbs. Conclusion:Both the step-up treatment strategy and the step-jump treatment strategy were safe and effective for treatment of IPN patients.

Objective:To evaluate the relationship of rotator cuff muscle function with shoulder abduction function after posterior superior rotator cuff tear via dynamic biomechanical study.Methods:By using the customized dynamic shoulder biomechanical testing system, seven freshly frozen cadaveric shoulders were used to stimulate shoulder abduction at 90° under four statuses: (1) intact rotator cuff with activation (normal rotator cuff group); (2) posterior superior rotator cuff tear with activation (posterior superior rotator cuff tear with activation group); (3) posterior superior rotator cuff tear with posterior superior rotator cuff deactivation (posterior superior rotator cuff tear with deactivation group); (4) none rotator cuff tissue above the geometric rotation center of the humeral head with deactivation (global tear group). The peak and stable value of middle deltoid force were used to evaluate biomechanical status in different rotator cuff tear conditions during shoulder abduction procedure. The peak subacromial pressure, average subacromial pressure, subacromial contact area, and subacromial force were used to evaluate subacromial pressed conditions under different rotator cuff tear conditions. The peak and stable ratio of glenohumeral contact force/middle deltoid force were used to evaluate shoulder stability under different rotator cuff tear conditions.Results:During dynamic abduction at 90°, the peak and stable value of middle deltoid force were (42.1±8.7)N and (29.9±7.4)N in normal rotator cuff group, (45.7±10.3)N and (30.5±7.2)N in posterior superior rotator cuff tear with activation group, and (48.4±13.4)N and (29.9±4.8)N in posterior superior rotator cuff tear with deactivation group (all P>0.05). But the peak and stable value of middle deltoid force were (69.7±9.7)N and (53.7±8.9)N in global tear group, significantly increased compared with other three groups (all P<0.05). The elevated middle deltoid force increased the subacromial contact pressure between glenohumeral head and acromion. The peak subacromial pressure, average subacromial pressure, subacromial contact area, and subacromial force were (0.40±0.05)MPa, (0.22±0.03)MPa, (7.71±5.09)mm 2, and (1.66±1.06)N respectively in normal rotator cuff group, (0.41±0.05)MPa, (0.26±0.07)MPa, (12.71±11.35)mm 2, and (2.93±2.46)N respectively in posterior superior rotator cuff tear with activation group, and (0.50±0.12)MPa, (0.26±0.07)MPa, (17.29±9.11)mm 2, and (4.09±1.46)N respectively in posterior superior rotator cuff tear with deactivation group (all P>0.05). However, the peak subacromial pressure, average subacromial pressure, subacromial contact area, and subacromial force were (3.64±1.70)MPa, (0.98±0.49)MPa, (47.63±11.91)mm 2, and (45.48±23.86)N respectively in global tear group, significantly higher than those in other three groups (all P<0.05). The peak and stable ratio of glenohumeral contact force/middle deltoid force were 2.24±0.30 and 2.46±0.13 in normal rotator cuff group, 2.21±0.19 and 2.52±0.08 in posterior superior rotator cuff tear with activation group, and 2.03±0.14 and 2.42±0.16 in posterior superior rotator cuff tear with deactivation group (all P>0.05). However, the peak and stable ratio of glenohumeral contact force/middle deltoid force were 1.40±0.14 and 1.52±0.41 in global tear group, significantly higher than those in other three groups (all P<0.05). No significant differences of the above parameters were observed in posterior superior rotator cuff tear with activation group, posterior superior rotator cuff tear with deactivation group and global tear group (all P>0.05). Conclusions:After posterior superior rotator cuff tear, rotator cuff muscle function does not affect the whole abduction function of shoulder. When the size of rotator cuff tear involves the whole superior humeral head rotation center, the normal abduction function of shoulder will be significantly impaired.

Objective:To analysis the impact of public health emergencies on mood fluctuations of depression and the related factors in the elderly in Shanghai, in order to provide a new evidence for early psychological intervention.Methods:A cross-sectional survey was conducted among 983 elderly in the Department of Geriatrics of Xinhua Hospital Affiliated to Shanghai Jiaotong University and two communities in Changning and Hongkou Districts of Shanghai by using a self-compiled social life questionnaire and Geriatric Depression Scale(GDS-30)during corona virus disease(COVID)-19 outbreak from 1 February to 15 February 2020.The mood fluctuations of depression and the related influencing factors were analyzed by comparing the current GDS-30 scores with the scores within previous six months.Results:Of 983 questionnaires, 867 were valid.The incidence of mild fluctuations of depression was increased from 20.9%(181/867)to 27.2%(235/867)during the public health emergencies( P<0.05), with 3 cases of newly emerged severe depression.The GDS-30 scores were higher during the public health emergencies than before the emergencies(9.88±3.85 vs.7.67±3.54, P<0.05). The four risk factors inducing fluctuations of depression in the elderly were the number of coexisted chronic diseases ≥2( P=0.036), the lack of visits or communication from families( P=0.015), the family members exposing a risk to COVID-19( P<0.01), and the daily viewing of epidemic news more than 4 h( P=0.023). Linear regression analysis showed that cough, sore throat, dizziness, sleep disturbance and dyspnea were significantly related to the aggravation of depression(based on the increase of GDS-30 score)( P<0.05). Conclusions:Public health emergencies may exacerbate depression in the elderly.They are more likely to experience the aggravation of depression when they suffer from multiple chronic diseases, lack the child visits or communications, have the family members exposing a risk to COVID-19 and pay excessive attention to the epidemic.

Objective:To demonstrate the concept of planning target volume (PTV) is not suitable for intensity proton therapy (IMPT) in lung cancer, plan differences were compared based on the concept of PTV and Internal target volume (ITV), aiming to provide clinical reference.Methods:Six patients were retrospectively selected and approved by the local ethics committee. Each of the six patients received two IMPT plans based on a synchronous accelerator model, developed by SINAP team (Shanghai Institute of Applied Physics, China Academy Science University) and commercial treatment system: one with the PTV-based robust IMPT (PTV-IMPT) plan and the other with ITV-based robust IMPT (ITV-IMPT) plan. Three beams were set in all plans, and the final dose was calculated using Monte Carlo dose algorithm. The plan quality and robustness of PTV-IMPT and ITV-IMPT plans were evaluated quantitatively.Results:Compared to the PTV-IMPT plan, ITV-IMPT plan showed better target conformity index (conformability index: 0.58 vs.0.43), better homogeneity index (homogeneity index: 0.96 vs.0.92), lower V 5Gy in normal lung tissue (13.1% vs.13.5%) and maximum dose in spinal cord (8.9 Gy vs. 9.5 Gy) as well as plan monitor unit (MU: 338 vs. 401) . In addition, ITV-IMPT plan showed more robust in target coverage (0.003-0.032 vs. 0.02-0.28), and normal lung tissue was also found a bit robust in the ITV-IMPT plan ( 0.06-0.11, 0.07-0.13). Conclusions:Compared with the PTV-IMPT plan, ITV-IMPT plan has the advantages of high planning quality, well robustness and better tumor motion mitigation. Therefore, ITV concept is recommended to be applied in the IMPT plan for lung cancer.

In recent years, the prevalence of metabolic diseases, including obesity, diabetes, nonalcoholic fatty liver disease, and metabolic syndrome, increased significantly. Fatigue is common in metabolic diseases and may lead to functional disability. This complicated feeling imposes a huge influence on patients with metabolic diseases physically and psychologically, which seriously affects the quality of life and brings serious burden to the social economy. There were an increasing number of researches on fatigue and metabolic diseases. This article reviews the evidences of the linkages between fatigue and metabolic diseases.

Objective: To investigate neglect among preschool children in two-child families in southwest Shandong Province, and to provide reference is for improving nursing parenting quality of two-child families. Methods: A questionnaire survey was conducted among 2 646 parents of two-child families and 2 074 parents of one-child families from 16 kindergartens in southwest Shandong Province. Results: The total neglect rate of two-child family preschool children in southwest Shandong Province was 27.37%, and the degree score of neglect was(40.15±5.51). The physical neglect rate(10.39%), emotional neglect rate(40.15±5.51), total neglect (38.15±4.88) and emotional neglect (46.12±6.91) of boys were higher than those of girls, and the difference was statistically significant(χ2/t=4.57, 6.65, 4.58, 4.72, P<0.05); No significant frequencies were found in total neglect rate, total neglect, neglect rate and neglect at all levels among all age groups(P>0.05); Among preschool children with siblings aged 7-<13, ≥13, total neglect rate(30.44%, 32.77%), emotional neglect rate(10.20%,12.00%), total neglect degree (44.71±5.98, 45.33±5.20) and emotional neglect degree (45.95±7.12, 48.86±4.97) of preschool children in two-child families have higher than those in onechild families, and the differences were of statistical significance(χ2/t=31.10, 4.55, 27.92, 24.13, 19.83, P<0.05); the total neglect rate(27.37%), emotional neglect rate(23.47%), emotional neglect (43.68±6.83) of twochild families and the total neglect (40.15±5.51) were higher than those of one-child families, and the differences were of statistical significance(χ2/t=4.98, 4.96, 3.76, 8.53, P<0.05). The age of siblings(OR=0.58), the education level of mothers(OR=0.64), and the main executor of family education (OR=1.54) were main factors to influence the child neglect of preschool children in two-child families(P<0.05). Conclusion Neglect of preschool children in two-child families is higher than that in one-child families in southwest Shandong, especially among those preschool boys and preschool children whose siblings were of school age.

In the original publication the grant number is incorrectly published. The correct grant number should be read as "17140901600". The corrected contents are provided in this correction article. This work was partially supported by grants from the National Natural Science Foundation of China (Nos. 81670470 and 81600149), a grant from the Shanghai Municipal Commission for Science and Technology (17140901600, 18411953500 and 15JC1400201) and a grant from National Key Research and Development Program (2016YFC0905100).

Adenosine ; genetics ; Adenosine Deaminase ; genetics ; metabolism ; Animals ; CRISPR-Associated Protein 9 ; genetics ; metabolism ; CRISPR-Cas Systems ; genetics ; Embryo, Mammalian ; metabolism ; Gene Editing ; Genetic Variation ; genetics ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Sprague-Dawley

This study aimed to elucidate the effect of tryptophan (Trp) on gut hormone secretion as well as the roles of the calcium-sensing receptor (CaSR) and its downstream signaling pathway in gut hormone secretion by assessing swine duodenal perfusion in vitro. Swine duodenum was perfused with Krebs-Henseleit buffer as a basal solution. Various concentrations (0, 10, and 20 mM) of Trp were applied to investigate its effect on gut hormone secretion. A CaSR antagonist was used to detect the involvement of CaSR and its signal molecules. The 20 mM Trp concentration promoted the secretion of cholecystokinin (CCK) and glucose-dependent insulinotropic peptide (GIP), elevated the mRNA level of CaSR, and upregulated the protein levels of CaSR, protein kinase C (PKC), and inositol trisphosphate receptor (IP3R). However, NPS 2143, an inhibitor of CaSR, attenuated the CCK and GIP release, reduced the mRNA level of CaSR, and decreased the protein levels of CaSR, PKC, and IP3R with 20 mM Trp perfusion. The results indicate that CCK and GIP secretion can be induced by Trp in swine duodenum in vitro, and the effect is mediated by CaSR and its downstream signal molecules PKC and IP3R.
Cholecystokinin ; Duodenum ; Gastric Inhibitory Polypeptide ; In Vitro Techniques ; Inositol ; Perfusion ; Protein Kinase C ; Receptors, Calcium-Sensing ; RNA, Messenger ; Swine ; Tryptophan