Objective: To examine the developmental trajectory of fine motor ability in schoolage children with attention deficit hyperactivity disorder (ADHD) for two years, so as to provide scientific evidence to promote motor development in ADHD children. Methods: From April to June 2019, 31 children aged 6-8 years old were selected from a public elementary school. They were diagnosed with ADHD by two psychiatric professionals according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Additionally, 31 typical developmental children, matched for age, sex and IQ with the ADHD group, were recruited as the control group. Fine motor ability was assessed with tasks of hand manual dexterity in Movement Assessment Battery for Children-2 (MACB-2), and a followup assessment was conducted from April to June 2021. The development changes of fine motor ability between two groups of children were compared by using t test and repeated measures analysis of variance. Results: Between baseline and followup periods after two years, the total score of hand fine motor in the ADHD group did not show significant improvement (7.4±3.0, 8.0±3.4; t=-1.05, P>0.05), while there was a small effect size improvement in typically developing control group (9.5±2.1, 10.5±2.4; t=-2.12, effect size=0.38, P<0.05). Followup after two years, coin/peg throwing scores with dominant hand improved between ADHD group and control group (7.0±3.3, 9.5±3.2; 8.4±2.8, 11.6±1.6) (t=-3.74, -6.33, P<0.01; effect size=0.67, 1.14), with a smaller improvement in the ADHD group. The score for threading beads/threads decreased in between ADHD group and control group (7.9±2.4, 5.8±3.1; 9.2±1.1, 8.2±1.9) (t=3.89, 2.78, P<0.01; effect size=0.70, 0.50), with a greater decrease in the ADHD group. Conclusions The development speed of fine motor ability in children with ADHD aged 6-8 is slow and continues to lag behind normal developmental children. Fine motor development in children with ADHD should be closely monitored, and targeted interventions should be implemented when necessary.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Objective:To observe the clinical effect of initiating continuous blood purification (CBP) treatment at different times for patients with severe acute pancreatitis (SAP), and to explore the optimal timing for starting CBP treatment for SAP, so as to provide evidence for clinicians to start CBP treatment.Methods:A retrospective cohort study was used to select patients with SAP who received CBP treatment in People's Hospital of Hunan Province from January 2020 to December 2023. According to the timing of CBP initiation, the patients were divided into early initiation group (diagnosis of SAP to the first CBP treatment time < 24 hours) and late initiation group (diagnosis of SAP to the first CBP treatment time of 24-48 hours). The general data, acute physiology and chronic health evaluationⅡ(APACHEⅡ), bedside index for severity in acute pancreatitis (BISAP) score and laboratory indicators, local complications and systemic complications, intensive care unit (ICU) treatment time, hospital stay, treatment cost, and clinical outcome of the two groups were collected and compared.Results:A total of 130 patients with SAP who received CBP treatment were enrolled, including 90 patients in the early initiation group and 40 patients in the late initiation group. Before treatment, there were no significant differences in gender, age, APACHEⅡscore, BISAP score, etiology and laboratory examination indexes between the early initiation group and late initiation group. At 48, 72, 96 hours after treatment, the blood calcium level of the two groups was significantly higher than that before treatment, and the levels of white blood cell count (WBC), C-reactive protein (CRP), lactic acid, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), APACHEⅡscore and BISAP score were significantly lower than those before treatment. The WBC level, APACHEⅡscore and BISAP score of the late initiation group were significantly lower than those of the early initiation group at 72 hours and 96 hours after treatment [WBC (×10 9/L): 10.96 (8.68, 13.04) vs. 12.45 (8.93, 16.30) at 72 hours after treatment, and 10.18 (8.68, 12.42) vs. 11.96 (8.81, 16.87) at 96 hours after treatment; APACHEⅡscore: 9.50 (5.75, 12.00) vs. 11.00 (6.25, 14.00) at 72 hours after treatment, and 10.00 (4.00, 12.00) vs. 12.00 (7.00, 14.75) at 96 hours after treatment; BISAP score: 2.35±1.03 vs. 2.76±1.10 at 72 hours after treatment, and 2.08±1.21 vs. 2.70±1.11 at 96 hours after treatment], the differences were statistically significant (all P < 0.05). In terms of complications, the incidence of pancreatic abscess in the late initiation group was significantly lower than that in the early initiation group [5.00% (2/40) vs. 20.00% (18/90)], but the incidence of abdominal compartment syndrome was significantly higher than that in the early initiation group [42.50% (17/40) vs. 13.33% (12/90)], the differences were statistically significant (all P < 0.05). In addition, the ICU treatment time in the early initiation group was significantly shorter than that in the late initiation group [days: 11.00 (6.00, 20.00) vs. 15.00 (9.75, 25.00), P < 0.05], and there were no statistically significant differences in hospitalization costs, length of stay and mortality between the two groups. Conclusions:CBP can effectively increase the level of blood calcium and decrease the level of lactic acid and inflammatory factors. Starting CBP within 24-48 hours after diagnosis of SAP can reduce WBC level and disease severity score faster, and reduce the occurrence of pancreatic abscess. Initiation of CBP within 24 hours after diagnosis of SAP can reduce the incidence of abdominal compartment syndrome and shorten the duration of ICU treatment.

Aneurysmal subarachnoid hemorrhage(aSAH)is one of the most damaging diseases in the brain.It is caused by multiple mechanisms and increased intracranial pressure is one of the most important.In clinical practice,it has been found that aSAH patients have a series of pathophysiological changes after increased intracranial pressure,which not only aggravates the secondary damage of brain tissue,but also becomes an unfavorable factor for the repair of damaged brain tissue.In many past studies on intracranial pressure,the application of intracranial pressure monitoring to guide the treatment of traumatic brain injury(TBI)patients has improved the prognosis of TBI patients,and intracranial pressure monitoring has become a routine clinical monitoring method.However,there are few clinical studies on intracranial pressure in aSAH patients,and it is not clear whether the research results and experience from TBI patients are applicable to the clinical practice of aSAH patients.The authors reviewed the reported clinical studies,and reviewed the change rule,application range and intervention threshold of intracranial presssure in aSAH patients.

OBJECTIVE: N6-methyladenosine (m ⁶A) is a common epigenetic modification in eukaryotes. In this study, we explore the potential impact of m ⁶A-associated single nucleotide polymorphisms (m ⁶A-SNPs) on heart failure (HF). METHODS: Data from genome-wide association studies (GWAS) investigating HF in humans and from m ⁶A-SNPs datasets were used to identify HF-associated m ⁶A-SNPs. Their functions were explored using expression quantitative trait locus (eQTL), gene expression, and gene enrichment analyses. Mediation protein quantitative trait locus (pQTL)-Mendelian randomization (MR) was used to investigate the potential mechanism between critical protein levels and risk factors for HF. RESULTS: We screened 44 HF-associated m ⁶A-SNPs, including 10 m ⁶A-SNPs that showed eQTL signals and differential expressions in HF. The SNP rs1801270 in CDKN1A showed the strongest association with HF ( P = 7.75 × 10 ^-6). Additionally, MR verified the genetic association between the CDKN1A protein and HF, as well as the mediating effect of blood pressure (BP) in this pathway. Higher circulating level of CDKN1A was associated with a lower risk of HF (odds ratio [ OR] = 0.82, 95% confidence interval [ CI]: 0.69 to 0.99). The proportions of hypertension, systolic BP, and diastolic BP were 48.10%, 28.94%, and 18.02%, respectively. Associations of PDIA6 ( P = 1.30 × 10 ^-2) and SMAD3 ( P = 4.80 × 10 ^-2) with HF were also detected. CONCLUSION Multiple HF-related m ⁶A-SNPs were identified in this study. Genetic associations of CDKN1A and other proteins with HF and its risk factors were demonstrated, providing new ideas for further exploration of the molecular mechanisms of HF.
Humans ; Polymorphism, Single Nucleotide ; Heart Failure/genetics* ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Cyclin-Dependent Kinase Inhibitor p21/metabolism* ; Quantitative Trait Loci ; Adenosine/metabolism* ; Male ; Female ; Genetic Predisposition to Disease

OBJECTIVE: To investigate the efficacy of arterial partial pressure of oxygen (PaO₂), procalcitonin (PCT) combined with ROX index in predicting the timing of tracheal intubation in patients with acute severe pancreatitis (SAP). METHODS: A case-control study was conducted. A total of 148 patients with SAP admitted to Hunan Provincial People's Hospital from January 2019 to December 2022 were selected as the research objects. According to whether endotracheal intubation was used after admission during hospitalization, the patients were divided into the intubation group (102 cases) and non-intubation group (46 cases). Gender, age, white blood cell count (WBC), lymphocyte count (LYM), platelet count (PLT), C-reactive protein (CRP), hemoglobin (Hb), PCT, PaO₂, arterial partial pressure of carbon dioxide (PaCO₂), arterial bicarbonate ion (HCO₃^-) 1 day after admission, arterial lactic acid (Lac), lactate dehydrogenase (LDH), heart rate (HR), respiratory rate (RR), pulse oxygen saturation (SpO₂), oxygenation index (PaO₂/FiO₂), blood pressure, worst ROX index (ROX index = SpO₂/FiO₂/RR) within 30 minutes of admission and 30 minutes before intubation of the two groups were measured. Multivariate Logistic regression was used to analyze the independent risk factors for the timing of endotracheal intubation in patients with SAP. The receiver operator characteristic curve (ROC curve) was used to determine the optimal predictive cut-off value for endotracheal intubation. RESULTS: There were no significant differences in age, gender, WBC, LYM, CRP, Hb, LDH, HR and blood pressure at admission between the two groups. The PLT, Lac, PCT and RR in the intubation group were significantly higher than those in the un-intubation group, and HCO₃^-, PaO₂, SpO₂, PaO₂/FiO₂, the worst ROX index within 30 minutes after admission and 30 minutes before intubation were significantly lower than those in the non-intubation group (all P < 0.05). Logistic regression analysis showed that the worst ROX index within 30 minutes before intubation was the largest negative influencing factor for the timing of tracheal intubation in SAP patients [odds ratio (OR) = 0.723, 95% confidence interval (95%CI) was 0.568-0.896, P = 0.000], followed by PaO₂ (OR = 0.872, 95%CI was 0.677-1.105, P < 0.001). PCT was the positive influencing factor (OR = 1.605, 95%CI was 1.240-2.089, P < 0.001). ROC curve analysis showed that the area under the ROC curve (AUC) of PaO₂, PCT, the worst ROX index within 30 minutes before intubation and the combination to evaluate the tracheal intubation time of patients with SAP were 0.715, 0.702, 0.722 and 0.808, the sensitivity was 78.1%, 75.0%, 81.5% and 89.3%, the specificity was 66.7%, 59.0%, 73.2% and 86.4%, and the best cut-off value was 60.23 mmHg (1 mmHg ≈ 0.133 kPa), 2.72 μg/L, 4.85, and 0.58, respectively. The AUC of the combination of PaO₂, PCT and the worst ROX index within 30 minutes before intubation predicted the timing of tracheal intubation in patients with SAP was significantly greater than using each index alone (all P < 0.01). CONCLUSIONS The worst ROX index within 30 minutes before intubation combined with PaO₂ and PCT is helpful for clinicians to make a decision for tracheal intubation in patients with SAP.
Humans ; Procalcitonin ; Oxygen ; Case-Control Studies ; Partial Pressure ; Retrospective Studies ; Pancreatitis/therapy* ; Intubation, Intratracheal ; Prognosis ; ROC Curve

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Objective To analyze the NBS-LRR disease resistance gene family of Codonopsis pilosula(Franch.)Nannf.and explore the disease resistance mechanism,so as to solve the problem of root rot disease of C.pilosula and promote the breeding and industrial development of C.pilosula.Methods Based on the transcriptome data of C.pilosula in response to root rot pathogen,gene structure,phylogeny,gene interaction and expression pattern of C.pilosula NBS-LRR family genes were analyzed by using bioinformatics methods.Results 88 NBS-LRR family genes were successfully identified.Including N,NL,CN,CNL,TN,TNL and PN,there are 50,14,1,14,4,3 and 2 genes respectively.Their physical and chemical properties,gene structure,phylogeny,gene interaction and expression pattern were analyzed.The results showed that CNL subfamily genes of C.pilosula were amplified during evolution;CNL and TNL gene structures ar-relatively conservative;Expression pattern analysis showed that there were differences in temporal expression patterns of C.pilosula NBS-LRR family genes under F.oxysporum infection.The highly expressed genes DN64786c1g6,DN64786c1g5,DN48234c0g2,DN54844c1g2,DN59747c0g3,DN56071c1g8,DN64591c1g1,DN48464c1g1,DN59886c0g1 play an important role in regulating the disease resistance of C.pilosula.The DN54844c1g2 may interact with GLR family,and then participate in immune regulation by regulating Ca2+ influx;DN64786c1g5 may interact with cytc-1 and cytc-2,and then participate in the response of C.pilosula to root rot by participating in redox reaction;DN59747c0g3 may interact with MPK3 and play an important role in the response of C.pilosula to root rot by participating in map signal cascade,phosphorylating WRKY transcription factor and participating in hypersensitivity reaction(HR).Conclusion The identification and expression analysis of NBS-LRR family genes of C.pilosula is of great significance to explore the mechanism of root rot resistance and gene function of C.pilosula..

Objective To observe the electromyography characteristics of children's handwriting with attention deficit hyperactivity disorder(ADHD),and explore its electrophysiological mechanism,so as to provide an objective basis for developing non-pharmacological treatment for such children.Methods Between September 2021 and April 2022,29 ADHD children were recruited from an ordinary public primary school and the psychiatric clinic of a class-3 grade-A hospital in Beijing.Among them,25 were boys and 4 were girls,with an average age of 8.21±1.78 years.Meanwhile,23 male and 5 fe-male healthy counterparts were selected with the age gap no more than 6 months.The Delsys wireless surface EMG system was used to collect the electromyographic signals of the abductor pollicis breve,the first dorsal interosseous muscle,the flexor radial carpi motor and the extensor finger muscles dur-ing their writing tasks such as tracing trajectories,writing Arabic numerals 0-9,26 small and capital English letters,Chinese characters one to ten and"Yong".The percentage of the averaged electromyog-raphy(AEMG)of a muscle in the sum value of all measured muscles,and the coefficient of differ-ence were selected to evaluate the muscle contribution rate and the consistency of exertion,respective-ly.Moreover,the independent sample t-test was employed to compare the two different groups with the significance set at α=0.05.Results There was a significant difference in the muscle contribution of abductor pollicis breve and first dorsal interosseous muscles when writing Arabic numerals and that of abductor pollicis breve muscles when writing Chinese characters between ADHD children(27.29%,25.58%and 27.53%)and their healthy counterparts(42.87%,19.96%and 37.13%)(P<0.05).Most muscle differentiation coefficients of ADHD children were higher than 100%,with that of the domi-nant hand radial wrist flexor muscle reaching 270%in the trajectory tracing task.Conclusion Accord-ing to the characteristics of EMG signals,school-age ADHD children show an immature writing pat-tern,including poor stability of writing-related muscles,insufficient control of small finger muscle groups,poor control of hand coordination,and insufficient muscle inhibition of non-dominant hand.It is recommended to conduct the electromyoelectric assessment of handwriting movements in ADHD chil-dren,so as to carry out targeted intervention at an early stage.

Objective:To analyze the effect of high-flow nasal cannula (HFNC) oxygen therapy in patients with acute respiratory failure, and investigate the indicators that predict the failure of HFNC.Methods:The clinical data of 174 patients with acute respiratory failure were retrospectively analyzed. The patients were treated with HFNC in the Emergency Department of Hunan Provincial People′s Hospital from January 2018 to September 2020. The vital signs, blood gas analysis, Borg score and ROX index of patients before and one hour after HFNC application were compared, and the application effect of HFNC was judged. The HFNC failure group was defined as patients with respiratory support upgraded to non-invasive ventilation, endotracheal intubation or death within 48 h, and the indicators for predicting the HFNC failure were analyzed.Results:The failure rate of HFNC was 24.13%(42/174). There were significant differences in the heart rate, SpO 2, systolic blood pressure, diastolic blood pressure and PaO 2 of successfal group before and after the use of HFNC, t values were -8.12-4.60, all P<0.05. Multivariate Logistic regression analysis showed that the change value of systolic blood pressure was a protective factor of the failure of HFNC ( OR=0.967, 95% CI were 0.949-0.985, P<0.05). Conclusions:The application of HFNC in patients with acute respiratory failure is feasible and effective, and the change value of systolic blood pressure is an indicator to predict the failure of HFNC.