[Objective] To study the molecular biological mechanism for a case of ABO blood group B subtype, and perform three-dimensional modeling of the mutant enzyme. [Methods] The ABO phenotype was identified by the tube method and microcolumn gel method; the ABO gene of the proband was detected by sequence-specific primer polymerase chain reaction (PCR-SSP), and the exon 6 and 7 of the ABO gene were sequenced and analyzed. Homologous modeling of Bw.03 glycosyltransferase (GT) was carried out by Modeller and analyzed by PyMOL2.5.0 software. [Results] The weakening B antigen was detected in the proband sample by forward typing, and anti-B antibody was detected by reverse typing. PCR-SSP detection showed B, O gene, and the sequencing results showed c.721 C>T mutation in exon 7 of the B gene, resulting in p. Arg 241 Trp. Compared with the wild type, the structure of Bw.03GT was partially changed, and the intermolecular force analysis showed that the original three hydrogen bonds at 241 position disappeared. [Conclusion] Blood group molecular biology examination is helpful for the accurate identification of ambiguous blood group. Homologous modeling more intuitively shows the key site for the weakening of Bw.03 GT activity. The intermolecular force analysis can explain the root cause of enzyme activity weakening.

ObjectiveTo analyze the current status, research hotspots, and development trends of transcranial ultrasound stimulation (TUS) in neurorehabilitation. MethodsRelevant literature on the application of TUS in neurological rehabilitation was retrieved from CNKI, Wanfang data, and Web of Science Core Collection, covering publications from inception to December 31, 2023. VOSviewer 1.6.20 and CiteSpace 6.2.R1 were used for visualized analysis. ResultsA total of 247 articles were included, with 124 in Chinese and 123 in English, showing an increasing trend in annual publications. The major contributors to English literature were China, the United States, Canada, France and South Korea. High-frequency Chinese keywords included transcranial ultrasound, neuromodulation, Parkinson's disease, stroke and clinical efficacy. The keyword clusters were transcranial ultrasound, neuromodulation, upper limb function and Parkinson's disease. Bursting keywords included rehabilitation, neural function, ultrasound therapy, closed-loop control and low intensity. High-frequency English keywords included focused ultrasound, deep brain stimulation, transcranial magnetic stimulation, blood-brain barrier and thalamotomy. Keyword clusters covered tissue plasminogen activator, ultrasonic imaging, transcranial magnetic stimulation, thalamotomy and ultrasound. Bursting keywords featured essential tremor, neurostimulation, direct current stimulation and transcranial ultrasound stimulation. ConclusionResearch on the application of TUS in neurorehabilitation is on the rise, focusing on its efficacy and safety in Parkinson's disease, essential tremor, and ischemic stroke. Future research needs to explore the mechanisms of TUS, optimize treatment plans, and promote the development of individualized therapies.

Phosphodiesterases(PDE)are involved in the regulation of cellular physiological processes and neurological functions,including neuronal plasticity,synapto-genesis,synaptic transmission,memory formation and cognitive functions by catalyzing the hydrolysis of intracellular cyclic adenosine monophosphate(cAMP)and cyclic guanosine monophosphate(cGMP).Many basic and clinical studies have shown that PDE4 inhibitors block or ameliorate the occurrence and development of central nervous system(CNS)diseases by inhibiting cAMP hydrolysis,increasing cAMP content and enhancing its downstream effects.PDE4 inhibitors have long-term potentiation effect,which can enhance phosphorylation of cAMP response element binding protein(CREB)and upregulate expression of memory related Arc genes in hippocampal neurons,thereby improving cognitive impairment and Alzheimer's disease-like symptoms.They can also delay the occurrence and development of Parkinson's disease by reducing the cytotoxicity induced by α-syn and increasing the effect of miR-124-3p on cell functions.Alteration of PDE4 activity is the molecular basis for psychosis and some cognitive disorders,therefore it is considered as a therapeutic target for schizophrenia.PDE4 inhibitors play a role in depression by inhibiting the advanced glycation end product receptor(RAGE),TLR4 and NLRP3 pathways in the hippocampus,reducing the activation of microglia and the production of IL-1β,down-regulating HMGB1/RAGE signaling pathway and inhibiting inflammatory factors.PDE4 inhibitor plays a role in the treatment of autism spectrum disorder by reducing the damage of cerebellar glial cells,increasing nociceptive threshold,and improving mutual learning and memory deficits.PDE4 inhibitors might be used in the treatment of fragile X syndrome by regulating the level of cAMP and affecting the expression of fragile X mental retardation protein(FMRP).PDE4 inhibitors can also promote the differentiation of oligodendrocyte progenitor cells and enhance myelination,which has potential in the treatment of multiple sclerosis.PDE4 is also related to bipolar disorder,which may be one of the therapeutic targets.At present,several PDE4 inhibitors are in clinical trials for the treatment of CNS diseases.This article reviews and discusses the progress on basic research and clinical trials of PDE4 inhibitors in CNS diseases,providing a reference for the prevention and treatment of CNS diseases and the development of new drugs.

Objective:To compare the effects of citrate and heparin anticoagulation on coagulation function and efficacy in children with septic shock undergoing continuous blood purification (CBP), and to provide guidance for CBP anticoagulation in children with septic shock.Methods:A case control study was conducted. Thirty-seven children with septic shock admitted to the pediatric intensive care unit (PICU) of the First Affiliated Hospital of Gannan Medical University from July 2019 to September 2022 were enrolled as the research subjects. The patients were divided into citrate local anticoagulation group and heparin systemic anticoagulation group according to different anticoagulation methods. The baseline data, the level of coagulation indicators [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), D-dimer] before treatment and 1 day after weaning from CBP, serum inflammatory mediators [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypersensitivity C-reactive protein (hs-CRP), procalcitonin (PCT)], bleeding complications during CBP and 7-day mortality were collected.Results:A total of 37 cases were enrolled finally, including 17 cases with citric acid local anticoagulation and 20 cases with heparin systemic anticoagulation. There was no statistically significant difference in general data such as gender, age, and body weight of children between the two groups. There were no statistically significant differences in baseline levels of coagulation indicators and inflammatory mediators before treatment of children between the two groups. One day after weaning from CBP, both groups showed varying degrees of improvement in coagulation indicators compared with those before treatment. Compared with before treatment, the PT of the heparin systemic anticoagulation group was significantly shortened after 1 day of weaning (s: 11.82±2.05 vs. 13.64±2.54), APTT and TT were significantly prolonged [APTT (s): 51.54±12.69 vs. 35.53±10.79, TT (s): 21.95±4.74 vs. 19.30±3.33], D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 4.94±3.94), with statistically significant differences (all P < 0.05). While in the citrate local anticoagulation group, only APTT was significantly prolonged after treatment compared with that before treatment (s: 49.28±10.32 vs. 34.34±10.32, P < 0.05). There were no statistically significant differences in other coagulation indicators compared with before treatment. Compared with the citric acid local anticoagulation group, the PT of the heparin systemic anticoagulation group was significantly shortened after treatment (s: 11.82±2.05 vs. 13.61±3.05, P < 0.05), and the D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 3.77±2.38, P < 0.01). The levels of inflammatory mediators in both groups were significantly reduced 1 day after CBP weaning compared with those before treatment [citric acid local anticoagulation group: hs-CRP (mg/L) was 12.53±5.44 vs. 22.65±7.27, PCT (μg/L) was 1.86±1.20 vs. 3.30±2.34, IL-6 (ng/L) was 148.48±34.83 vs. 202.32±48.62, TNF-α (ng/L) was 21.38±7.71 vs. 55.14±15.07; heparin systemic anticoagulation group: hs-CRP (mg/L) was 11.82±4.93 vs. 21.62±8.35, PCT (μg/L) was 1.90±1.08 vs. 3.18±1.97, IL-6 (ng/L) was 143.81±33.41 vs. 194.02±46.89, TNF-α (ng/L) was 22.44±8.17 vs. 56.17±16.92, all P < 0.05]. However, there was no statistically significant difference between the two groups (all P > 0.05). There was no statistically significant difference in bleeding complication during CBP and 7-day mortality in children between the citrate local anticoagulation group and the heparin systemic anticoagulation group (5.9% vs. 30.0%, 17.6% vs. 20.0%, both P > 0.05). Conclusions:Heparin for systemic anticoagulation and regional citrate anticoagulation can significantly reduce the levels of IL-6, TNF-α, hs-CRP and PCT in children with septic shock, and relieve inflammatory storm. Compared with citric acid local anticoagulation, heparin systemic anticoagulation can shorten the PT and reduce the level of D-dimer in children with septic shock, which may benefit in the prevention and treatment of disseminated intravascular coagulation (DIC).

Objective:To improve clinicians' understanding of congenital nephrogenital diabetes insipidus (CNDI) and to reduce missed and misdiagnosis. Methords 　Based on the literature, the clinical data and gene mutation of 2 patients with CNDI who were admitted to the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Henan University of Science and Technology on July 30, 2020 were analyzed retrospectively. Results:(1) The presentee, 4 years old, had irritable thirst, polydipsia and polyuria for more than 3 years. The sister, 2.5 years old, had irritable thirst, polydipsia and polyuria for more than 2 years. The clinical diagnosis was “CNDI”, and the symptoms improved after treatment with hydrochlorothiazide. (2) The genetic test revealed that the congenital nephrogenic uremia and her sister had a heterozygous mutation of c.170A>C (p.Q57P) and c.211G>A (p.Vl71M) in the aquaporin-2 gene, and the mother carried the AQP2 gene. c.170A>C(p.Q57P) mutation.Conclusion:CNDI is a rare disease. Early diagnosis and treatment can improve the prognosis of patients to the greatest extent, and prenatal diagnosis can guide eugenics.

Patients with hepatocellular carcinoma (HCC) and bone metastasis (BM) suffer from greatly reduced life quality and a dismal prognosis. However, BM in HCC has long been overlooked possibly due to its relatively low prevalence in previous decades. To date, no consensus or guidelines have been reached or formulated for the prevention and management of HCC BM. Our narrative review manifests the increasing incidence of HCC BM to sound the alarm for additional attention. The risk factors, diagnosis, prognosis, and therapeutic approaches of HCC BM are detailed to provide a panoramic view of this disease to clinicians and specialists. We further delineate an informative cancer bone metastatic cascade based on evidence from recent studies and point out the main factors responsible for the tumor-associated disruption of bone homeostasis and the formation of skeletal cancer lesions. We also present the advances in the pathological and molecular mechanisms of HCC BM to shed light on translational opportunities. Dilemmas and challenges in the treatment and investigation of HCC BM are outlined and discussed to encourage further endeavors in the exploration of underlying pathogenic and molecular mechanisms, as well as the development of novel effective therapies for HCC patients with BM.
Bone Neoplasms/secondary* ; Carcinoma, Hepatocellular/therapy* ; Humans ; Liver Neoplasms/therapy* ; Prognosis

Background: Autoimmune pancreatitis (AIP) is a chronic pancreatitis associated with immune factors. IgG4-related sclerosing cholangitis (IgG4-SC) is a common extrapancreatic manifestation of AIP, however, its optimal treatment still needs to be clarified. Aims: To summarize the experience in the clinical diagnosis and treatment of AIP, especially IgG4-SC. Methods: Twenty-five patients with AIP admitted from the First Affiliated Hospital of Nanchang University between January 2015 and May 2021 were recruited, and a retrospective analysis was conducted on the clinical symptoms, laboratory and imaging findings, pathological results, as well as the treatment regimens and clinical outcomes. Results: All the patients were diagnosed as type 1 AIP (84.0% male, mean age 63.5 years). Obstructive jaundice (56.0%) and epigastric pain (44.0%) were the main clinical symptoms. The main imaging findings were diffuse enlargement of the pancreas, capsule-like rim, and distal biliary stricture associated with intra- and extra-hepatic duct dilation. The serum IgG4 elevated significantly. In 14 patients with IgG4-SC, the total bilirubin was between 1-2 upper limit of normal (ULN) in 3 cases, between 2-5 ULN in 3 cases, and > 5×ULN in 8 cases. Fifteen (83.3%) patients obtained pathological diagnosis by endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA). Six IgG4-SC patients were treated with steroids alone, and 6 received biliary stenting with or without steroids, no differences in liver function tests were existed between the two groups prior to treatment (all P> 0.05). Liver function tests in most of these patients were normalized after treatment. Conclusions: AIP is a rare disease in clinical practice, and is more frequently seen in elderly male patients. Biliary involvement (IgG4-SC) is common and often presents initially as obstructive jaundice, which can be effectively managed with steroids alone, without the need for biliary stenting.

Objective:To study the changes of left atrial volume and function in patients with acute myocardial infarction (AMI) by three-dimensional echocardiography (3DE) and magnetic resonance imaging (MRI).Methods:Thirty-one patients with AMI in Henan People′s Hospital from March to October 2020 were selected as AMI group and 30 healthy subjects were selected as control group.The left atrial maximum volume (LAVmax), minimum volume (LAVmin), presystolic volume (LAVpre), volume index(LAVI), emptying volume (LAEV), ejection fraction (LAEF), long axis and circumferential strain (LASr, LASr-c; LAScd, LAScd-c; LASct, LASct-c) were measured by two-dimensional echocardiography (2DE), 3DE left atrial automatic quantitative technique and CMR.The differences of left atrial indices between two groups and among 2DE, 3DE left atrial automatic quantitative and CMR techniques were compared. Pearson correlation coefficient and Bland-Altman analysis were used to compare 2DE, 3DE left atrial automatic quantitative and CMR. Intra-observer and inter-observer repeatability of 2DE, 3DE left atrial automatic quantitative technique and CMR were evaluated by intra-group correlation coefficient (ICC).Results:①Compared with the control group: LAVmax, LAVmin, LAVpre, LAVI, LASct and LASct-c by 3DE left atrial automatic quantitative increased, while LAEV, LAEF, LASr, LASr-c, LAScd and LAScd-c by 3DE left atrial automatic quantitative technique decreased in AMI group (all P<0.05). ②LAVmax, LAVmin, LAVpre, LASr, LAScd, LASct measured by 3DE left atrial automatic quantitative were more strongly related to CMR than that measured by 2DE(all P<0.05). Compared with CMR, 2DE underestimated LAVmax, LAVmin, LAVpre, LASr, LAScd, LASct by (8.01±4.01)ml, (9.03±4.15)ml, (7.26±2.09 )ml, (7.26±1.23)%, (5.02±1.08)%, (6.24±0.43)%(all P<0.05); 3DE left atrial automatic quantitative technique underestimated LAVmax, LAVmin, LAVpre, LASr, LAScd, LASct by (1.67±0.62)ml, (1.95±0.90)ml, (2.52±0.76)ml, (1.97±0.59)%, (2.03±0.39)%, (1.02±0.30)% (all P>0.05); The time-consuming of 2DE and 3DE left atrial automatic quantitative technique was reduced, and the time-consuming of 3DE left atrial automatic quantitative technique was less than 2DE [(12.18±3.24)s vs (73.34±10.37)s]. ③The reproducibility of 2DE, 3DE left atrial automatic quantitative technique and CMR measurement within and between observers were good. Conclusions:3DE left atrial automatic quantitative technique can effectively evaluate the changes of left atrial volume and function in patients with AMI. Compared with 2DE and CMR, it is simple, rapid, accurate and repeatable, which provides a new and effective method for clinical study of cardiovascular diseases.

Objective:To systematically evaluate the effect of hydrocortisone combined with vitamin C and vitamin B1 on the efficacy of patients with sepsis or septic shock.Methods:Databases including CNKI, Sino Med, VIP, Wanfang, PubMed, the Cochrane Library, and Embase were searched from inception to January 2021 for the randomized controlled trial (RCT) about hydrocortisone combined with vitamin C and vitamin B1 to treat sepsis or septic shock. The experimental group was given intravenous injection of hydrocortisone, vitamin B1 and vitamin C based on conventional treatment; the control group was given conventional treatment or placebo/hydrocortisone/hydrocortisone+vitamin B1 based on conventional treatment. Outcome indicators included sequential organ failure assessment (SOFA), mortality, the duration of vasoactive drugs, new acute kidney injury (AKI) patients, length of stay in intensive care unit (ICU) and in hospital. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. RevMan 5.3 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias.Results:A total of 6 articles involving 816 patients were included, with 411 patients in the experimental group and 405 patients in the control group. The Meta-analysis results showed that the duration of vasoactive drugs in the experimental group was significantly shorter than that in the control group [mean difference ( MD) = -24.02, 95% confidence interval (95% CI) was -32.36 to -15.68, P < 0.000 01]. However, there were no significant differences in SOFA, mortality, new AKI patients, the length of ICU stay and hospital stay between the two groups [SOFA: MD = -0.14, 95% CI was -1.15 to 0.87, P = 0.79; mortality: relative risk ( RR) = 0.99, 95% CI was 0.81 to 1.21, P = 0.92; new AKI patients: RR = 1.10, 95% CI was 0.42 to 2.87, P = 0.84; length of ICU stay: MD = 1.33, 95% CI was -2.22 to 4.89, P = 0.46; length of hospital stay: MD = 1.02, 95% CI was -0.66 to 2.69, P = 0.23]. The funnel plot showed that most of the points were symmetrical and showed an inverted funnel shape, suggesting that the publication bias among the studies was small. There was no significant publication bias on this Meta-analysis. Conclusions:Hydrocortisone combined with vitamin C and vitamin B1 can shorten the duration of vasoactive drugs in patients with sepsis or septic shock, but it cannot effectively reduce the SOFA score, mortality, new AKI patients, length of stay in ICU and in hospital. Limited by the number and quality of the included studies, further large-scale, multi-center, blinded, RCT are still needed for verification.