The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (I_h) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism* ; Hyperalgesia/metabolism* ; Cyclin-Dependent Kinase 5/metabolism* ; Neuralgia/metabolism* ; Male ; Anxiety/metabolism* ; Mice ; Potassium Channels/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Pyramidal Cells/metabolism*

Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90％confidence interval(CI)of the geometric mean ratio(GMR)were 94.11％-118.06％,99.22％-107.74％and 99.16％-107.44％for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00％-125.00％.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90％CI of GMR were 96.99％-101.19％and 97.17％-101.41％for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00％-125.00％.The 95％upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00％-125.00％.The incidence of adverse events in fasting and fed studies was 22.86％and 22.92％,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.

The current research status of different structures,driving modes and training modes of hand rehabilitation robots at home and abroad was introduced.The disadvantages of the existing hand rehabilitation robots were analyzed.It's pointed out hand rehabilitation robots in the future would involve in the combination of rigid and flexible wearing,new intelligent driving mode and multi-mode rehabilitation training.[Chinese Medical Equipment Journal,2024,45(11):88-96]

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow/pathology* ; Exons ; Humans ; Janus Kinase 2/genetics* ; Middle Aged ; Mutation ; Mutation, Missense ; Polycythemia Vera/genetics* ; Young Adult

Objective: To analyze the clinical characteristics of SARS-CoV-2 Omicron variant infected children in convalescence in Tianjin. Methods: A total of 104 pediatric patients infected by SARS-CoV-2 Omicron variant Tianjin First Central Hospital (designated hospital for SARS-CoV-2 infection in Tianjin) for convalescent treatment from January 22^nd, 2022 to February 24^th were included for a retrospective study.Clinical data including clinical typing, SARS-CoV-2 IgG and IgM test and 2019-nCoV nucleic acid test were collected.The cases were divided into 2-dose group and zero-dose group based on the doses of inactivated SARS-CoV-2 vaccine. The children were divided into repositive group and negative group, according to the nucleic acid test during hospitalization. Chi-square test was used for the comparison between the groups. Results: The age of these 104 children was 10.0 (0.3, 14.0) years on admission, 53 children were males and 51 were females, 92 cases (88.5%) had mild symptoms, 12 cases (11.5%) had common symptoms.The age and SARS-CoV-2 IgG level of zero-dose group was lower (2.0 (0.3, 10.2) vs. 10.0 (3.2, 14.0) years, 10 (2, 17) vs. 193 (157, 215), χ²=-5.57, Z=-48.76,both P<0.001) than that of 2-dose group. The zero-dose group had a high rate of transmission among family members and a high level of SARS-CoV-2 IgM level (13/14 vs. 62.2% (56/90), 0.4 (0.2, 0.8) vs. 0.4 (0.2, 1.1),χ²=5.09, Z=-48.95, both P<0.05) than the 2-dose group. Repositive group had a high rate of underlying diseases and SARS-CoV-2 IgM level was higher (2/13) vs. 1.1% (1/91), (0.6 (0.2, 1.0) vs. 0.3 (0.2, 0.7), χ²=8.29, Z=2.70, both P<0.05) than negative group. The SARS-CoV-2 IgG level of repositive group was lower than that of negative group (160 (78, 197) vs. 213 (186, 231), χ²=-3.20, P<0.05). Conclusions: Children infected with SARS-CoV-2 Omicron variant in Tianjin were mainly transmitted by family members, and most of them had mild symptoms. Two-dose group had higher IgG levels and lower IgM levels than zero-dose group.The probability of SARS-CoV-2 nucleic acid test repositivity increased in children with underlying diseases and lower IgG levels.
Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Child ; Female ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Male ; Nucleic Acids ; Retrospective Studies ; SARS-CoV-2

Abstract: - （ ） ， Work related musculoskeletal disorders WMSDs are common occupational diseases in construction workers which have a high prevalence rate and involve a large number of construction workers. WMSDs affect daily work and quality of life of ， patients leading to absenteeism and burden. The main body parts of construction workers suffering from WMSDs are lower back/ ， ， ， ， ， waist neck shoulder knee elbow and hand/wrist and most of the patients are complicated in multiple sites. The prevalence ， of WMSDs varies by site with the lower back/waist being the most common sites. The influencing factors of WMSDs in （ ， ， ， ， ， construction workers mainly include individual factors age years of work gender smoking status sleep habits physical ， ）， （ ， ， ， fitness and physical exercise etc. occupational factors work load job type working posture work organization and ， ） management working environment and social psychological factors. The incidence of WMSDs is the result of multiple factors. ， ， Therefore tertiary prevention is the key to the prevention and control of WMSDs especially the etiological prevention. Chinese ， construction industry is in the period of rapid development and the demand of construction workers is large. It is urgent to carry out epidemiological and intervention studies on WMSDs for construction workers to guide the formulation of relevant guidelines and measures for prevention and control of WMSDs.

Abstract: - （ ） ， Work related musculoskeletal disorders WMSDs are common occupational diseases in construction workers which have a high prevalence rate and involve a large number of construction workers. WMSDs affect daily work and quality of life of ， patients leading to absenteeism and burden. The main body parts of construction workers suffering from WMSDs are lower back/ ， ， ， ， ， waist neck shoulder knee elbow and hand/wrist and most of the patients are complicated in multiple sites. The prevalence ， of WMSDs varies by site with the lower back/waist being the most common sites. The influencing factors of WMSDs in （ ， ， ， ， ， construction workers mainly include individual factors age years of work gender smoking status sleep habits physical ， ）， （ ， ， ， fitness and physical exercise etc. occupational factors work load job type working posture work organization and ， ） management working environment and social psychological factors. The incidence of WMSDs is the result of multiple factors. ， ， Therefore tertiary prevention is the key to the prevention and control of WMSDs especially the etiological prevention. Chinese ， construction industry is in the period of rapid development and the demand of construction workers is large. It is urgent to carry out epidemiological and intervention studies on WMSDs for construction workers to guide the formulation of relevant guidelines and measures for prevention and control of WMSDs.

Abstract: - （ ） ， Work related musculoskeletal disorders WMSDs are common occupational diseases in construction workers which have a high prevalence rate and involve a large number of construction workers. WMSDs affect daily work and quality of life of ， patients leading to absenteeism and burden. The main body parts of construction workers suffering from WMSDs are lower back/ ， ， ， ， ， waist neck shoulder knee elbow and hand/wrist and most of the patients are complicated in multiple sites. The prevalence ， of WMSDs varies by site with the lower back/waist being the most common sites. The influencing factors of WMSDs in （ ， ， ， ， ， construction workers mainly include individual factors age years of work gender smoking status sleep habits physical ， ）， （ ， ， ， fitness and physical exercise etc. occupational factors work load job type working posture work organization and ， ） management working environment and social psychological factors. The incidence of WMSDs is the result of multiple factors. ， ， Therefore tertiary prevention is the key to the prevention and control of WMSDs especially the etiological prevention. Chinese ， construction industry is in the period of rapid development and the demand of construction workers is large. It is urgent to carry out epidemiological and intervention studies on WMSDs for construction workers to guide the formulation of relevant guidelines and measures for prevention and control of WMSDs.