OBJECTIVES: To investigate the role of a neural pathway from oxytocin (OXT) neurons in the paraventricular hypothalamic nucleus (PVN) to γ-aminobutyric acid (GABA) neurons (GABAergic neurons) in the trigeminal nucleus caudalis (TNC) in regulating pain sensitization in a mouse model of chronic migraine and to explore the underlying mechanisms. METHODS: A chronic migraine mouse model was established by intraperitoneal injection of nitroglycerin (NTG, 1 mg/mL, 10 mg/kg) on days 1, 3, 5, 7, and 9. The study consisted of four parts: PartⅠ: 24 male wild-type C57BL/6J mice were divided into four groups (n=6 in each), receiving single or repeated injection of NTG or saline, respectively. Immunofluorescence was used to detect c-Fos and OXT expression in the PVN. Part Ⅱ: 6 male OXT-Cre transgenic C57BL/6J mice were used for anterograde monosynaptic tracing combined with RNAscope and immunofluorescence to identify neural projections from PVN OXT neurons to TNC GABAergic neurons. Part Ⅲ: 30 male OXT-Cre transgenic C57BL/6J mice were bilaterally injected Cre-dependent chemogenetic activation virus into the PVN. These mice were randomly divided into five groups, with six mice in each group. Mice in the clozapine N-oxide (CNO) group and the control group were intra-peritoneally injected with 0.1 mg/mL of CNO solution (1 mg/kg) and the same volume of isotonic normal saline, respectively. 3 hours after the injection, the brain tissues were harvest and c-Fos immunofluorescence staining was performed to verify the efficiency of chemogenetic activation virus. Mice in the model control group and the CNO activated model group were subjected to chronic migraine modeling, with bilateral TNC injection of isotonic normal saline and CNO, respectively, on day 10. The mice in the negative control group were bilaterally intra-TNC injected with isotonic normal saline. After 30 minutes, the Von-Frey filament and acetone tests were used to assess the mechanical pain threshold and cold pain response time in the periorbital region of the mice in these three groups. Part Ⅳ: 24 male OXT-Cre transgenic C57BL/6J mice were bilaterally injected with the Cre-dependent chemogenetic activation virus into the PVN. These mice were randomly divided into four groups, with six mice in each group. Mice in the model control group, the CNO activated model group and the atosiban group were subjected to chronic migraine modeling. On day 10, mice in the negative control group and the model control group were intraperitoneally injected with isotonic normal saline, while mice in the CNO activated model group and the atosiban group were intraperitoneally injected with CNO. After 15 minutes, mice in the atosiban group were bilaterally intra-TNC injected with atosiban, while mice in other three groups were bilaterally intra-TNC injected with isotonic normal saline containing 1% dimethyl sulfoxide. After 15 minutes, the Von-Frey filament and acetone tests were used to assess the mechanical pain threshold and cold pain response time in the periorbital region of the mice. The GABA content in the bilateral TNC was detected by high-performance liquid chromatography (HPLC). RESULTS: Mice with chronic migraine models exhibited reduced periorbital mechanical pain thresholds and increased periorbital cold pain reaction time, accompanied by an increase in both the number of c-Fos⁺ neurons and the percentage of c-Fos⁺ OXT neurons in the PVN (all P<0.05). The anterograde tracing virus and RNAscope combined with immunofluorescence staining showed that PVN OXT neurons projected to TNC GABAergic neurons. Immuno-fluorescence staining demonstrated that compared with the control group, the percentage of c-Fos⁺ OXT neurons in the PVN of CNO group increased (P<0.05). In bilateral intra-TNC drug administration experiments, compared with the model control group, the periorbital mechanical pain threshold increased, and the periorbital cold pain reaction time decreased in the CNO activated model group (both P<0.05). In intraperitoneal drug administration experiments, compared with the CNO activate model group, the periorbital mechanical pain threshold decreased, and the periorbital cold pain reaction time increased in the atosiban group (both P<0.05). HPLC analysis showed that, compared with the negative control group, the model control group and the atosiban group, GABA level of TNC in the CNO activated model group increased (all P<0.05). CONCLUSIONS PVN OXT neurons exert a descending facilitatory effect on GABAergic neurons in the TNC via OXT release, thereby ameliorating pain sensitization in chronic migraine.
Animals ; Paraventricular Hypothalamic Nucleus/physiopathology* ; Male ; Mice, Inbred C57BL ; Migraine Disorders/physiopathology* ; Mice ; GABAergic Neurons/physiology* ; Oxytocin/physiology* ; Disease Models, Animal ; Neurons/physiology* ; Mice, Transgenic ; Neural Pathways ; Chronic Disease

Objective:To investigate the effect of Early infarct growth rate(EIGR) on the prognosis of patients with acute large vessel occlusive ischemic stroke.Methods:A total of 164 patients with acute large vessel occlusive ischemic stroke were enrolled in the emergency department of the First Affiliated Hospital of Nanjing Medical University from January 1, 2020 to December 31, 2022.According to the change of the National Institutes of Health Stroke Scale (NIHSS) score at admission and 72 h after treatment, the patients were divided into good prognosis group and poor prognosis group. The basic clinical data of the two groups were observed and compared. The risk factors of poor prognosis were analyzed by univariate regression. The effect of EIGR on prognosis after age stratification was further analyzed.Results:Comparing the clinical data of the two groups, there was no difference in EIGR (mL/h) (7.67 vs. 8.24, P=0.211) between the two groups. The product between EIGR and age was included as the interaction term, and the result of the interaction term in the model was statistically significant ( OR=1.002, 95% CI: 1.000-1.003, P=0.032) .Moreover, the result was still statistically significant after adjusting for relevant variables (gender, history of hypertension, history of atrial fibrillation, history of diabetes, history of coronary heart disease, and history of stroke) ( OR=1.002, 95% CI:1.000-1.003, P=0.027). Subgroup analysis was performed according to the median age (71 years). In the elderly group, the proportion of poor prognosis was higher with fast core infarction growth rate defined by 25 mL/h and 15 mL/h ( P < 0.05).In the younger age group, there was no significant difference in the proportion of poor prognosis in the fast core infarction growth rate compared with the slow type ( P > 0.05). Conclusions:EIGR can predict the early clinical outcome early in elderly patients with large vessel occlusive ischemic stroke.

Objective:To study the standardization path of medical ultrasound equipment management based on total quality management,and to improve the service level of medical ultrasound equipment in clinical diagnosis and treatment activities.Methods:According to the process of medical ultrasound equipment use,the risk nodes were determined,the formation path and damage probability of equipment use risk were analyzed by probabilistic graphical model,and the standardized path of medical ultrasound equipment use was formulated based on time control and standardized use mode.35 medical ultrasound equipment in clinical use in The People's Hospital of Jianyang from 2022 to 2023 were selected,the use and management of 33 medical ultrasound equipment in 2022 were managed in the conventional management mode(33 units),and the use and management of 35 medical ultrasound equipment in 2023(2 new units)were adopted in the total quality management mode.The difference in equipment operation quality,risk ratio and service effect under different modes were compared.Results:The failure rates of medical ultrasound diagnostic equipment,medical ultrasound treatment equipment and other medical ultrasound equipment using the total quality management model were(0.763±0.68)%,(0.833±0.65)%and(0.969±0.64)%,respectively,which were lower than those of the conventional management mode,the difference was statistically significant(t=3.331,5.348,5.940,P<0.05).The proportion of risk problems such as component damage,delayed diagnosis and treatment,resource waste and social impact of medical ultrasound equipment using total quality management mode were(2.023±0.99)‰,(1.569±0.89)‰,(2.541±1.05)‰ and(1.238±0.63)‰,respectively,which were lower than those of the conventional management mode,the difference was statistically significant(t=3.935,3.676,5.699,3.189,P<0.05).The scores of clinicians,nurses,operating technicians,equipment engineers and management personnel involved in the use and management of medical ultrasound equipment were for the service effect of the total quality management model were(95.797±2.13)points,(93.880±2.12)points,(94.605±1.91)points,(91.387±3.20)points and(96.275±1.82)points,respectively,which were higher than those of the conventional management mode,the difference was statistically significant(t=4.536,5.477,6.869,2.943,4.673,P<0.05).Conclusion:The standardized path of medical ultrasound equipment management based on total quality management can improve the operation quality of equipment,reduce the incidence of clinical use risk,and enhance the level of clinical service.

Objective:To evaluate the safety and effectiveness of the model repair strategy for preputial defect in hypospadias surgery.Methods:From February 2017 to December 2022, 59 children in our hospital with an average age of (6.9±3.2) years were retrospectively analyzed. All of them were children with multiple failed hypospadias operations. According to the condition of penile scrotum skin, different methods of penile skin reconstruction were selected. Among them, 20 patients underwent penile skin flap reconstruction with simple foreskin and multiple small incision reduction, 22 patients with penile and scrotal transposition underwent penile lateral scrotum flap to complete ventral penis coverage, and 12 patients underwent middle scrotum flap with pedicled flap to cover ventral urethra. The penis was covered by inferior epigastric artery perforator flap in 5 patients.Results:The wound healed completely one week after the operation and no obvious scar formation was observed. The ventral flap of the penis was covered by the lateral scrotal flap of the penis, and no flap necrosis and wound infection were observed. The ventral urethra was covered with pedicled skin flap in the middle scrotal suture. The flap survived without scrotal hematoma. The inferior epigastric artery perforator flap was used to cover the patients with penile defect, all the flaps survived, and no complications such as wound infection and abdominal hernia occurred. No urethral fistula or urethral diverticulum was reported in all the patients. Urethral stricture occurred in 1 case of scrotal suture pedicled flap group and 1 case of lateral penis scrotal flap group, which was cured after expansion. One case with small incision and one case with lateral scrotal skin were cured after secondary repair by Mathieu method.Conclusions:For children with a history of multiple hypospadias operations, coverage of ventral skin defects of the penis is essential to reduce complications and obtain good appearance. This study summarized four effective strategies for covering penile defect from simple to complex. The small incision was used to reduce the expansion of all flaps. The lateral penile scrotal flap is more suitable for patients with penile scrotal transposition. The pedicled flap of scrotal suture and inferior superficial artery perforator flap are suitable for the repair of larger defect area.

Objective:Early identification of ischemic stroke patients with large vessel occlusion can improve referral efficiency and shorten reperfusion time. The purpose of this study was to analyze the characteristics of patients with large vessel occlusion and identify factors that could predict large vessel occlusion.Methods:The clinical data of 432 patients with ischemic stroke treated through emergency green channel were retrospectively analyzed, and the differences between the large vessel occlusion group (LVO group) and the non-large vessel occlusion group (non-LVO group) were compared, and two independent risk factors of the LVO group were screened out by logistics regression analysis: baseline NIHSS score and D-dimer value. The predicted cutoff values of NIHSS score and D-dimer were further determined by the receiver operating characteristic (ROC) curve.Results:A total of 432 patients with ischemic stroke had complete imaging data, with a mean age of 68.5±12.4 years, including 275 (63.7%) males, and 245 (56.7%) in the LVO group and 187 (43.3%) in the non-LVO group. Age, hemorrhagic transformation, thrombolytic therapy, endovascular treatment, atrial fibrillation, baseline NIHSS score [14.0 (6.0-20.0) vs. 3.0 (1.0-6.0), P<0.05], and D-dimer value at admission [0.9(0.4-2.3) mg/L vs. 0.3 (0.2-0.5)mg/L, P<0.05] were statistically significant different between the two groups. Multivariate Logistic regression analysis showed that higher baseline NIHSS score( OR=1.22,95% CI: 1.17-1.27)and higher D-dimer value( OR=3.10,95% CI: 2.14-4.47)were independent risk factors for large vessel occlusion. Baseline NIHSS score combined with D-dimer value was a good predictor of large vessel occlusion(AUC 0.85 [0.81-0.89]). ROC curve suggested that NIHSS score >6.5 and D-dimer >0.57 mg/L were the cutoff values for predicting large vessel occlusion. Conclusions:Higher baseline NIHSS score and D-dimer value are valuable for early prediction of large vessel occlusion, patients with NIHSS score >6.5 points and D-dimer >0.57 mg/L should be promptly transported to an advanced stroke center for treatment.

ObjectiveTo analyze the epidemic intensity and characteristics of influenza in Changzhou City， Jiangsu Province from 2019 to 2023， and to provide scientific evidence for the formulation of influenza prevention and control strategies. MethodsThe surveillance data of influenza surveillance sentinel hospitals in Changzhou City from April 2019 to March 2023 were collected through the China influenza surveillance information system. Influenza-like illness （ILI） cases before and after the pandemic of COVID-19 in Changzhou City were analyzed， and the differences among qualitative data were compared by using χ^² test. ResultsFrom April 2019 to March 2023 the percentages of ILI cases’ medical visits in the four-influenza surveillance year were 2.57%， 1.84%， 5.38%， and 3.66%， respectively， and the positive detection rates of influenza virus were 25.71%， 0.44%， 22.78%， and 24.32%， respectively. The number of influenza outbreaks was 61， 1， 23， and 128， respectively. ILI cases were mainly among adolescent children aged 5‒14 years. The percentage of ILI cases in 2020‒2021 after the pandemic of COVID-19 was significantly lower than that in 2019‒2020 （χ²=737.342， P<0.001）， and the percentage of ILI cases in 2021‒2023 was higher than that in 2019‒2020. Influenza viruses in 2019‒2021 were dominated by type B Victoria， and influenza A virus was the dominant strain in positive influenza virus detections in 2022‒2023. The number of influenza outbreaks in 2021‒2023 was significantly lower than that in 2019‒2020 （χ²=185.662， P<0.001）. ConclusionThe epidemiological characteristics of influenza are different in different stages of COVID-19 prevention and control during 2019‒2023. In the dynamic clearance phase of COVID-19， ILI case’s medical visits showed low-level fluctuations without obvious seasonal fluctuations， and influenza virus was dominated by type B. In the high-intensity phase of the pandemic， the level of ILI case’s medical visits has reached the peak of the calendar year， and the positive detection of influenza virus was dominated by type A H3N2. In the "Category B B control" phase， the level of ILI case’s medical visits increased after a rapid decline， and the positive detection of influenza virus was dominated by type A H1N1. It is necessary to further strengthen the monitoring of influenza cases， pay close attention to the changes in influenza strains， actively promote influenza vaccination for key population group， and promote health behavior changes for the whole population.

OBJECTIVE: To study the genetic variants of a child with Autism Spectrum Disorder (ASD) combined with epilepsy, and explore its possible pathogenic mechanism. METHODS: Clinical data of the child were collected and evaluated, whole-exome sequencing (WES) technology was used to explore the genetic variants sites of the child and his parents and candidate genes were filtered out. Sanger sequencing were performed to verify the variants identified by WES and PolyPhen2 was utilized to predict the function of these variants. qPCR was carry out to determine the expression of the variant gene. RESULTS: The proband carried a compound heterozygous mutation in the SIK3 gene (Chr11 q23.3, NM_025164.6), which contains a missense mutation c.1295A>G (p.N432S) inherited from the father and a deletion [c.2389_2391del(p.797del)] inherited from the mother. Both mutation sites are highly conservative, and PolyPhen2 predicted (c.1295A>G [p.N432S]) to be harmful. Compared to the mother, expression of SIK3in mRNA level in the peripheral blood of the proband and his father were both significantly decreased; compared to normal child, SIK3 expression in the peripheral blood of the proband and two other children with ASD were all decreased significantly too. In addition, studies on mice found that Sik3 gene has a marked higher level of expression in the brain. CONCLUSION The SIK3 gene variants may probably be associated with ASD. The detailed mechanism needs to be studied further, which may involve lipid metabolism dysfunction in the brain.
Animals ; Autism Spectrum Disorder/genetics* ; Epilepsy/genetics* ; Male ; Mice ; Mutation ; Mutation, Missense ; Protein Kinases ; Protein Serine-Threonine Kinases/genetics* ; Whole Exome Sequencing

ObjectiveTo explore the related factors of troublemaking behaviors among patients with mental disorders induced by amphetamine-type stimulants （ATS）， and to provide references for the formulation of relevant intervention measures for ATS-induced mental disorders. MethodsA total of 105 patients who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） for ATS-induced mental disorders were included， and classified into troublemaking group and non-troublemaking group. The general demographic data and clinical data of the selected individuals were collected， and all patients were assessed using Social Support Rating Scale （SSRS）. Then univariate analysis and multivariate Logistic regression model were used to screen the related factors of troublemaking behaviors. ResultsThe scores of SSRS， objective support dimension and social support utilization dimension were significantly lower in troublemaking group than those in non-troublemaking group， with statistical differences ［（24.10±6.59） vs. （28.94±5.59）， t=3.364， P=0.001； （5.50±1.96） vs. （8.20±2.13）， t=5.183， P<0.01； （4.60±2.26） vs. （6.28±1.90）， t=3.435， P=0.001］. Multivariate Logistic regression analysis showed that male （OR=6.061， P=0.014） was a risk factor， while high social support level （OR=0.873， P=0.018） was the protective factor for troublemaking behaviors among patients with ATS-induced mental disorders. ConclusionPatients with ATS-induced mental disorders of the males and with low social support level are at high risk of troublemaking behaviors.

Unicompartmental knee arthroplasty(UKA) is an important surgical technique for the treatment of end-stage knee osteoarthritis, which has high requirement for the position and angle of the prosthesis. The application of three-dimensional(3D) printed in UKA reflects several characteristics such as accuracy,efficiency and safety,but the current research results show that there is still lack of consistency in the design of 3D printed guides and the standard of prosthetic position parameters. This article reviews the history, manufacturing requirements and process of 3D printed guides during UKA surgery, as well as the results of current clinical research. Whether 3D printed guides can safely and effectively improve the placement accuracy of inexperienced doctors during UKA surgery,and whether the long-term results are worthy of clinical promotion need further verification.

Unicompartmental knee arthroplasty(UKA) is an important surgical technique for the treatment of end-stage knee osteoarthritis, which has high requirement for the position and angle of the prosthesis. The application of three-dimensional(3D) printed in UKA reflects several characteristics such as accuracy,efficiency and safety,but the current research results show that there is still lack of consistency in the design of 3D printed guides and the standard of prosthetic position parameters. This article reviews the history, manufacturing requirements and process of 3D printed guides during UKA surgery, as well as the results of current clinical research. Whether 3D printed guides can safely and effectively improve the placement accuracy of inexperienced doctors during UKA surgery,and whether the long-term results are worthy of clinical promotion need further verification.