Deciphering the role of wound healing genes in skin cutaneous melanoma: Insights into expression, methylation, mutations, and therapeutic implications.

Skin Cutaneous Melanoma (SKCM) is a form of cancer that originates in the pigment-producing cells, known as melanocytes, of the skin. Delay wound healing is often correlated with the occurrence of and progression of SKCM. In this comprehensive study, we investigated the intricate roles of two important wound healing genes in SKCM, including Matrix Metalloproteinase-2 (MMP2) and Matrix Metalloproteinase-9 (MMP9). Through a multi-faceted approach, we collected clinical samples, conducted molecular experiments, including RT-qPCR, bisulphite sequencing, cell culture, cell Counting Kit-8, colony formation, and wound healing assays. Beside this, we also used various other databases/tools/approaches for additional analysis including, UALCAN, GEPIA, HPA, MEXPRESS, cBioPortal, KM plotter, DrugBank, and molecular docking. Our results revealed a significant up-regulation of MMP2 and MMP9 in SKCM tissues compared to normal counterparts. Moreover, promoter methylation analysis suggested an epigenetic regulatory mechanism. Validations using TCGA datasets and immunohistochemistry emphasized the clinical relevance of MMP2 and MMP9 dysregulation. Functional assays demonstrated their synergistic impact on proliferation and migration in SKCM cells. Furthermore, we identified potential therapeutic candidates, Estradiol and Calcitriol, through drug prediction and molecular docking analyses. These compounds exhibited binding affinities, suggesting their potential as MMP2/MMP9 inhibitors. Overall, our study elucidates the diagnostic, prognostic, and therapeutic implications of MMP2 and MMP9 in SKCM, shedding light on their complex interplay in SKCM occurrence and progression.

Role of HCN channels in the functions of basal ganglia and Parkinson's disease.

Parkinson's disease (PD) is a motor disorder resulting from dopaminergic neuron degeneration in the substantia nigra caused by age, genetics, and environment. The disease severely impacts a patient's quality of life and can even be life-threatening. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a member of the HCN1-4 gene family and is widely expressed in basal ganglia nuclei. The hyperpolarization-activated current mediated by the HCN channel has a distinct impact on neuronal excitability and rhythmic activity associated with PD pathogenesis, as it affects the firing activity, including both firing rate and firing pattern, of neurons in the basal ganglia nuclei. This review aims to comprehensively understand the characteristics of HCN channels by summarizing their regulatory role in neuronal firing activity of the basal ganglia nuclei. Furthermore, the distribution and characteristics of HCN channels in each nucleus of the basal ganglia group and their effect on PD symptoms through modulating neuronal electrical activity are discussed. Since the roles of the substantia nigra pars compacta and reticulata, as well as globus pallidus externus and internus, are distinct in the basal ganglia circuit, they are individually described. Lastly, this investigation briefly highlights that the HCN channel expressed on microglia plays a role in the pathological process of PD by affecting the neuroinflammatory response.

[Application of multiomics mass spectrometry in the research of chemical exposome].

Environmental factors, such as environmental pollutants, behaviors, and lifestyles, are the leading causes of chronic noncommunicable diseases. Estimates indicate that approximately 50% of all deaths worldwide can be attributed to environmental factors. The exposome is defined as the totality of human environmental (i.e., all nongenetic) exposures from conception, including general external exposure (e.g., climate, education, and urban environment), specific external exposure (e.g., pollution, physical activity, and diet), and internal exposure (e.g., metabolic factors, oxidative stress, inflammation, and protein modification). As a new paradigm, this concept aims to comprehensively understand the link between human health and environmental factors. Therefore, a comprehensive measurement of the exposome, including accurate and reliable measurements of exposure to the external environment and a wide range of biological responses to the internal environment, is of great significance. The measurement of the general external exposome depends on advances in environmental sensors, personal-sensing technologies, and geographical information systems. The determination of exogenous chemicals to which individuals are exposed and endogenous chemicals that are produced or modified by external stressors relies on improvements in methodology and the development of instrumental approaches, including colorimetric, chromatographic, spectral, and mass-spectrometric methods. This article reviews the research strategies for chemical exposomes and summarizes existing exposome-measurement methods, focusing on mass spectrometry (MS)-based methods. The top-down and bottom-up approaches are commonly used in exposome studies. The bottom-up approach focuses on the identification of chemicals in the external environment (e.g., soil, water, diet, and air), whereas the top-down approach focuses on the evaluation of endogenous chemicals and biological processes in biological samples (e.g., blood, urine, and serum). Low- and high-resolution MS (LRMS and HRMS, respectively) have become the most popular methods for the direct measurement of exogenous and endogenous chemicals owing to their superior sensitivity, specificity, and dynamic range. LRMS has been widely applied in the targeted analysis of expected chemicals, whereas HRMS is a promising technique for the suspect and unknown screening of unexpected chemicals. The development of MS-based multiomics, including proteomics, metabolomics, epigenomics, and spatial omics, provides new opportunities to understand the effects of environmental exposure on human health. Metabolomics involves the sum of all low-molecular-weight metabolites in a living system. Nontargeted metabolomics can measure both endogenous and exogenous chemicals, which would directly link exposure to biological effects, internal dose, and disease pathobiology, whereas proteomics could play an important role in predicting potential adverse health outcomes and uncovering molecular mechanisms. MS imaging (MSI) is an emerging technique that provides unlabeled in-depth measurements of endogenous and exogenous molecules directly from tissue and cell sections without changing their spatial information. MSI-based spatial omics, which has been widely applied in biomarker discovery for clinical diagnosis, as well as drug and pollutant monitoring, is expected to become an effective method for exposome measurement. Integrating these response measurements from metabolomics, proteomics, spatial omics, and epigenomics will enable the generation of new hypotheses to discover the etiology of diseases caused by chemical exposure. Finally, we highlight the major challenges in achieving chemical exposome measurements.

Ameliorating parkinsonian motor dysfunction by targeting histamine receptors in entopeduncular nucleus-thalamus circuitry.

In Parkinson's disease (PD), reduced dopamine levels in the basal ganglia have been associated with altered neuronal firing and motor dysfunction. It remains unclear whether the altered firing rate or pattern of basal ganglia neurons leads to parkinsonism-associated motor dysfunction. In the present study, we show that increased histaminergic innervation of the entopeduncular nucleus (EPN) in the mouse model of PD leads to activation of EPN parvalbumin (PV) neurons projecting to the thalamic motor nucleus via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to postsynaptic H2R. Simultaneously, this effect is negatively regulated by presynaptic H3R activation in subthalamic nucleus (STN) glutamatergic neurons projecting to the EPN. Notably, the activation of both types of receptors ameliorates parkinsonism-associated motor dysfunction. Pharmacological activation of H2R or genetic upregulation of HCN2 in EPNPV neurons, which reduce neuronal burst firing, ameliorates parkinsonism-associated motor dysfunction independent of changes in the neuronal firing rate. In addition, optogenetic inhibition of EPNPV neurons and pharmacological activation or genetic upregulation of H3R in EPN-projecting STNGlu neurons ameliorate parkinsonism-associated motor dysfunction by reducing the firing rate rather than altering the firing pattern of EPNPV neurons. Thus, although a reduced firing rate and more regular firing pattern of EPNPV neurons correlate with amelioration in parkinsonism-associated motor dysfunction, the firing pattern appears to be more critical in this context. These results also confirm that targeting H2R and its downstream HCN2 channel in EPNPV neurons and H3R in EPN-projecting STNGlu neurons may represent potential therapeutic strategies for the clinical treatment of parkinsonism-associated motor dysfunction.

Clinical Characteristics of and Treatment Strategy for Hydrocephalus in Patients With Severe Disorders of Consciousness.

Abstract Making an appropriate diagnosis and administering effective treatment for hydrocephalus in patients with severe disorders of consciousness (DOC) remains controversial and difficult. Given that the typical symptoms are usually concealed by the limited behavioral responsiveness of patients with severe DOC, hydrocephalus diagnosis is likely to be missed in the clinic. Even if not, the presence of hydrocephalus may reduce the likelihood of DOC recovery, posing a conundrum for clinicians. From December 2013 to January 2023, the clinical data and therapeutic schedule of hydrocephalus in patients with severe DOC at Huashan Hospital's Neurosurgical Emergency Center were studied retrospectively. Sixty-eight patients (mean age [± SD] 52.53 ± 17.03 years, 35 males and 33 females) with severe DOC were included. The hydrocephalus was discovered after computed tomography (CT) or magnetic resonance imaging (MRI) revealed enlarged ventricles in the patients. During hospitalization, patients underwent a surgical treatment that included a ventriculoperitoneal (V-P) shunt and/or cranioplasty (CP) implantation. Following the surgery, an individualized V-P pressure was established based on the patient's ventricle size and neurological function variation. To account for the improvement in consciousness in patients with severe DOC, Glasgow Coma Scale (GCS) and Coma Recovery Scale-Revised (CRS-R) assessments were performed before and after hydrocephalus treatment. All patients with severe DOC had varying degrees of ventricular enlargement, deformation, and poor brain compliance. Approximately 60.3% (41/68) of them had low- or negative-pressure hydrocephalus (LPH or NegPH). Of the patients, 45.5% (31/68) had a one-stage V-P shunt and CP operation performed concurrently, whereas the remaining 37 patients had a single V-P shunt operation performed independently. Besides two patients with DOC who developed surgical complications, 92.4% (61/66) of the survivors showed an improvement in consciousness after hydrocephalus treatment. In patients with severe DOC, LPH or NegPH was common. Secondary hydrocephalus in patients with DOC had been largely ignored, hampering their neurological rehabilitation. Even months or years after the onset of severe DOC, active treatment of hydrocephalus can significantly improve patients' consciousness and neurological function. This study summarized several evidence-based treatment experiences of hydrocephalus in patients with DOC.

Clinical Decision on Disorders of Consciousness After Acquired Brain Injury: Stepping Forward.

Major advances have been made over the past few decades in identifying and managing disorders of consciousness (DOC) in patients with acquired brain injury (ABI), bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration. Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools, sophisticated neuroimaging, and electrophysiological techniques, a considerably higher diagnostic accuracy rate of DOC may now be reached. During the treatment of patients with DOC, a variety of intervention methods are available, including amantadine and transcranial direct current stimulation, which have both provided class II evidence, zolpidem, which is also of high quality, and non-invasive stimulation, which appears to be more encouraging than pharmacological therapy. However, heterogeneity is profoundly ingrained in study designs, and only rare schemes have been recommended by authoritative institutions. There is still a lack of an effective clinical protocol for managing patients with DOC following ABI. To advance future clinical studies on DOC, we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC. We propose a preliminary clinical decision protocol, which could serve as an ideal reference tool for many medical institutions.

Histamine bidirectionally regulates the intrinsic excitability of parvalbumin-positive neurons in the lateral globus pallidus and promotes motor behaviour.

BACKGROUND AND PURPOSE: Parvalbumin (PV)-positive neurons are a type of neuron in the lateral globus pallidus (LGP) which plays an important role in motor control. The present study investigated the effect of histamine on LGPPV neurons and motor behaviour. EXPERIMENTAL APPROACH: Histamine levels in LGP as well as its histaminergic innervation were determined through brain stimulation, microdialysis, anterograde tracing and immunostaining. Mechanisms of histamine action were detected by immunostaining, single-cell qPCR, whole-cell patch-clamp recording, optogenetic stimulation and CRISPR/Cas9 gene-editing techniques. The effect of histamine on motor behaviour was detected by animal behavioural tests. KEY RESULTS: A direct histaminergic innervation in LGP from the tuberomammillary nucleus (TMN) and a histamine-induced increase in the intrinsic excitability of LGPPV neurons were determined by pharmacological blockade or by genetic knockout of the histamine H1 receptor (H1 R)-coupled TWIK-related potassium channel-1 (TREK-1) and the small-conductance calcium-activated potassium channel (SK3), as well as by activation or overexpression of the histamine H2 receptor (H2 R)-coupled hyperpolarization-activated cyclic nucleotide-gated channel (HCN2). Histamine negatively regulated the STN → LGPGlu transmission in LGPPV neurons via the histamine H3 receptor (H3 R), whereas blockage or knockout of H3 R increased the intrinsic excitability of LGPPV neurons. CONCLUSIONS AND IMPLICATIONS: Our results indicated that the endogenous histaminergic innervation in the LGP can bidirectionally promote motor control by increasing the intrinsic excitability of LGPPV neurons through postsynaptic H1 R and H2 R, albeit its action was negatively regulated by the presynaptic H3 R, thereby suggesting possible role of histamine in motor deficits manifested in Parkinson's disease (PD).

EGF­IL2 bispecific and bivalent EGF fusion toxin efficacy against syngeneic head and neck cancer mouse models.

The epidermal growth factor receptor (EGFR) remains one of the best molecules for developing targeted therapy for multiple human malignancies, including head and neck squamous cell carcinoma (HNSCC). Small molecule inhibitors or antibodies targeting EGFR have been extensively developed in recent decades. Immunotoxin (IT)­based therapy, which combines cell surface binding ligands or antibodies with a peptide toxin, represents another cancer treatment option. A total of 3 diphtheria toxin (DT)­based fusion toxins that target human EGFR­monovalent EGFR IT (mono­EGF­IT), bivalent EGFR IT (bi­EGF­IT), and a bispecific IT targeting both EGFR and interleukin­2 receptor (bis­EGF/IL2­IT) were recently generated by the authors. Improved efficacy and reduced toxicity of bi­EGF­IT compared with mono­EGF­IT in immunocompromised HNSCC mouse models was reported. In the present study, bis­EGF/IL2­IT were generated using a unique DT­resistant yeast expression system and evaluated the in vitro and in vivo efficacy and toxicity of the 3 EGF­ITs in immunocompetent mice. The results demonstrated that while the three EGF­ITs had different efficacies in vitro and in vivo against HNSCC, bi­EGF­IT and bis­EGF/IL2­IT had significantly improved in vivo efficacy and remarkably less off­target toxicity compared with mono­EGF­IT. In addition, bis­EGF/IL2­IT was superior to bi­EGF­IT in reducing tumor size and prolonging survival in the metastatic model. These data suggested that targeting either the tumor immune microenvironment or enhancing the binding affinity could improve the efficacy of IT­based therapy. Bi­EGF­IT and bis­EGF/IL2­IT represent improved candidates for IT­based therapy for future clinical development.

Receptor and Ionic Mechanism of Histamine on Mouse Dorsolateral Striatal Neurons.

The dorsolateral striatum (DLS) is the critical neural substrate that plays a role in motor control and motor learning. Our past study revealed a direct histaminergic projection from the tuberomammillary nucleus (TMN) of the hypothalamus to the rat striatum. However, the afferent of histaminergic fibers in the mouse DLS, the effect of histamine on DLS neurons, and the underlying receptor and ionic mechanisms remain unclear. Here, we demonstrated a direct histaminergic innervation from the TMN in the mouse DLS, and histamine excited both the direct-pathway spiny projection neurons (d-SPNs) and the indirect-pathway spiny projection neurons (i-SPNs) of DLS via activation of postsynaptic H1R and H2R, albeit activation of presynaptic H3R suppressed neuronal activity by inhibiting glutamatergic synaptic transmission on d-SPNs and i-SPNs in DLS. Moreover, sodium-calcium exchanger 3 (NCX3), potassium-leak channels linked to H1R, and hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) coupled to H2R co-mediated the excitatory effect induced by histamine on d-SPNs and i-SPNs in DLS. These results demonstrated the pre- and postsynaptic receptors and their downstream multiple ionic mechanisms underlying the inhibitory and excitatory effects of histamine on d-SPNs and i-SPNs in DLS, suggesting a potential modulatory effect of the central histaminergic system on the DLS as well as its related motor control and motor learning.

Epidemiological characteristics and spatio-temporal distribution of pulmonary tuberculosis cases reported in students from Guizhou Province, 2011-2020 / 中华流行病学杂志

Objective: To analyze the trend of epidemiological characteristics and spatiotemporal distribution of pulmonary tuberculosis (PTB) among smear-positive or other types of students in Guizhou Province from 2011 to 2020, and to provide a reference for improving prevention and control measures. Methods: Data were collected from the Chinese Information System's Notifiable Disease and Tuberculosis Management Information System for disease control and prevention, the Joinpoint 4.9.1.0 software was used to analyze the trend of registration rate; the ArcGIS 10.6 software was used to construct a ring map and to perform spatial autocorrelation analysis; the SaTScan 9.7 software was used for spatial-temporal scan statistics. Results: A total of 32 682 student PTB cases were reported in Guizhou Province from 2011 to 2020, including 5 949 (18.20%) smear-positive cases. Most cases occurred from high school students of 16 to 18 years old (43.99%, 14 376/32 682); the annual average registered rate was 36.22/100 000, the highest in 2018 (52.90/100 000), and the registration rate showed an increasing trend. Meanwhile, a similar trend of registration rate was observed among smear-positive or other types of students. The spatialtemporal heterogeneity was found that the "high-high" clustering patterns of smear-positive or other types were aggregated in Bijie City. Six spatialtemporal clusters with statistically significant (all P<0.001) were detected among smear-positive or other cases, respectively. Conclusions: Upward trend with spatial- temporal clusters of PTB cases reported in students from Guizhou Province from 2011 to 2020. Surveillance should be strengthened for high school students, and regular screening should be conducted in high-risk areas to control the source of infection and reduce the risk of transmission.

Key quality attributes of benchmark samples of famous classical formula Kaixin Powder / 中国中药杂志

We prepared 15 batches of Kaixin Powder benchmark samples with the decoction pieces of different batches. Further, we established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples and analyzed the peaks and similarity of the chromatograms. With sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, β-asarone, α-asarone, and dehydropachymic acid as index components, the index component content determination method was established and 70%-130% of the mean content of each component was set as the range. The chromatograms of 15 batches of Kaixin Powder benchmark samples had a total of 22 characteristic peaks, among which 8 peaks were identified, which represented sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, β-asarone, α-asarone, and dehydropachymic acid, respectively. The chromatograms shared the similarity of 0.992-0.999. The 15 batches of benchmark samples had sibiricose A5 of 0.34-0.55 mg·g~(-1), sibiricose A6 of 0.43-0.57 mg·g~(-1), polygalaxanthone Ⅲ of 0.12-0.19 mg·g~(-1), 3,6'-disinapoyl sucrose of 1.08-1.78 mg·g~(-1), ginsenoside Rb_1 of 0.33-0.62 mg·g~(-1), β-asarone of 2.34-3.72 mg·g~(-1), α-asarone of 0.11-0.22 mg·g~(-1), and dehydropachymic acid of 0.053-0.079 mg·g~(-1). This study established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples, and the method was simple, feasible, reproducible, and stable. This study provides a scientific basis for further research on the key chemical properties of the benchmark samples and preparations of Kaixin Powder.

Hypomethylation of Thyroid Peroxidase as a Biomarker for Hepatocellular Carcinoma with Tumor Thrombosis.

OBJECTIVE: Thyroid hormones (THs) regulate multiple physiological activities in the liver, including cellular metabolism, differentiation, and cell growth, and play important roles in the pathogenesis of hepatocellular carcinoma (HCC). Thyroid peroxidase (TPO) is a key molecule involved in the THs synthesis and signaling pathway. As an epigenetic modification, DNA methylation has a critical role in tumorigenesis with diagnostic potential. However, the connection between THs and DNA methylation has been rarely investigated. METHODS: The methylation of key TH-related genes was analyzed by in-house epigenome-wide scanning, and we further analyzed the methylation levels of the TPO promotor in 164 sample pairs of HCC and adjacent non-cancerous tissues by Sequenom EpiTYPER assays, and evaluated their clinical implications. RESULTS: We identified that the methylation of the TPO promoter was downregulated in the HCC tissues (P<0.0001) with a mean difference ranging from 18.5% to 22.3%. This methylation pattern correlated with several clinical factors, including a multi-satellite tumor, fibrous capsule, and the presence of tumor thrombus. The receiver operator characteristic (ROC) curve analysis further confirmed that the percent methylated reference (PMR) values for TPO were predictive of the tumor [the area under the curve (AUC) ranged from 0.755 to 0.818] and the thrombosis in the HCC patients (the AUC ranged from 0.706 to 0.777). CONCLUSION: These findings demonstrated that epigenetic alterations of TPO, as indicated by the PMR values, were a potential biomarker for HCC patients with tumor thrombosis.

Neuroinflammation Following Traumatic Brain Injury: Take It Seriously or Not.

Traumatic brain injury (TBI) is associated with high mortality and disability, with a substantial socioeconomic burden. With the standardization of the treatment process, there is increasing interest in the role that the secondary insult of TBI plays in outcome heterogeneity. The secondary insult is neither detrimental nor beneficial in an absolute sense, among which the inflammatory response was a complex cascade of events and can thus be regarded as a double-edged sword. Therefore, clinicians should take the generation and balance of neuroinflammation following TBI seriously. In this review, we summarize the current human and animal model studies of neuroinflammation and provide a better understanding of the inflammatory response in the different stages of TBI. In particular, advances in neuroinflammation using proteomic and transcriptomic techniques have enabled us to identify a functional specific delineation of the immune cell in TBI patients. Based on recent advances in our understanding of immune cell activation, we present the difference between diffuse axonal injury and focal brain injury. In addition, we give a figurative profiling of the general paradigm in the pre- and post-injury inflammatory settings employing a bow-tie framework.

Three cases of mediastinal germ cell tumors and concurrent hematologic malignancy and literature review / 中华实用儿科临床杂志

To analyze the clinical characteristics, treatment and prognosis of mediastinal germ cell tumors (GCTs) with concurrent hematologic malignancy (HM). The clinical features, treatment and prognosis of 3 cases of HM associated with mediastinal GCTs treated in the Department of Medical Oncology, Beijing Children′s Hospital from November 2014 to September 2018 were retrospectively analyzed.Meanwhile, relevant cases were searched in the PubMed and Wanfang database from their establishment to December 2019.Three male cases of HM associated with mediastinal GCTs aged from 12 to 16 years.The pathogenesis of mediastinal masses suggested teratoma or yolk sac tumor.All of them were treated with surgery and chemotherapy.Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) was diagnosed respectively at 5 months, 9 months and 31 months after initial GCTs in the 3 cases.Two patients died and 1 child survived at the last follow-up.A total of 135 cases of concurrent GCTs and HM (or leukemia) were reviewed in online databases, involving 127 cases (94.1%) with the mediastinal GCTs associated with HM and 8 cases(5.9%) with GCTs related HM from another original sites.One hundred and twenty-six cases (99.2%) were male and the median age of GCTs diagnosis was 22 (10-48) years.Fifty-three cases (41.7%) were teratoma and 94 cases (74.0%) were GCTs containing teratoma with or without yolk sac tumor.Among the types of HM, 72 cases (56.7%) were AML and 31 cases (24.4%) were AML-M7.The median interval between GCTs and HM was 3 (0-122) months.Forty-six cases (36.2%) presented 2 malignancies simultaneously.HM were diagnosed within 12 months of GCTs in 85 cases (66.9%). The survival data were known in 107 cases, involving 94 (87.9%) deaths and 13 (12.1%) survivors.The median survival time after diagnosis of HM was 2 (0-48) months.The tendency of HM must be highly concerned in adolescent male patients with primary mediastinal GCTs, especially those with yolk sac tumor or teratoma.Their prognoses are very poor.Allogeneic hematopoietic stem cell transplantation is an alternative treatment.

Treatment of bifid ribs by gasless endoscopy using lift device / 中华胸心血管外科杂志

Objective:Gasless laparoscopic surgery using lifting device was first introduced in 1993 mainly for general surgery and gynecology. Here we report its application in bifid rib treatment and explore the feasibility and safety of the surgery.Methods:From July 2008 to December 2019, according to the enrollment criteria, 278 patients of bifid ribs were treated at the Department of Thoracic Surgery, Beijing Children’s Hospital, Capital Medical University, including 183 males and 95 females, the mean age was(5.7±2.5) years old. There were 242 cases of single bifid rib and 36 cases of multiple bifid ribs. The bifid ribs were more common on the right side, as 184 cases had bifid ribs on right side, while only 68 cases on the left side and 26 cases on both sides. Patients’ clinical data were retrospectively summarized and analyzed, including the patients’ gender, age, location and type of bifid rib, perioperative outcome, and follow-up.Results:All the 278 patients successfully completed the operation. The abnormality was most frequently found in the fifth rib(incidence ranking: fifth > fourth > third > sixth). The mean operation time was(64.5±16.1)min, and the mean blood loss was(4.8±2.1)ml. No serious complications occurred during the surgery. Follow-up was done for 7 to 120 months, and no recurrent patients were observed.Conclusion:Gasless endoscopy with lifting device has been used as a safe and effective method to treat bifid ribs in our hospital. This surgery leads to less injury, smaller incision, and no scars on the front chest. Gasless endoscopic surgery with lifting device can be one of the options for correcting bifid ribs.

Diagnosis and treatment of rare esophageal hamartoma in children / 中华胸心血管外科杂志

Objective:To summarize the clinical features, diagnosis and treatment experience of esophageal hamartoma in children.Methods:From December 2013 to December 2019, 3 cases of esophageal hamartoma were admitted to our hospital, and a retrospective analysis was conducted.Results:There were 1 male and 2 females, with an average age of 6.4 years old. The clinical manifestations were vomiting in 2 cases and dysphagia with esophageal foreign body sensation in 1 case. Esophagography, chest contrast-enhanced CT, and esophagoscopy showed esophageal stenosis or esophageal mass effectg, and esophageal dilatation above the affected segment. The tumor was found in upper esophagus in 1 case and lower esophagus in 2 cases. Tumors were complete resection in all 3 cases and the patients were discharged smoothly. All the 3 cases were followed up after surgery for 10-74 months(average 37 months), and 1 case had gastroesophageal reflux. No stenosis or recurrence was found in all the cases, and all the patients could eat normal diet.Conclusion:The main manifestations of esophageal hamartoma in children are vomiting and choking. Complete surgical resection is the main treatment method, and the prognosis is good.

A case report of Joubert syndrome caused by KIAA0586 gene mutation / 中华实用儿科临床杂志

The main clinical phenotypes, imaging features and genetic test results of a child with Joubert syndrome treated in Shenzhen Children′s Hospital in July 2020 were analyzed retrospectively, and the literature on Joubert syndrome was summarized.The main manifestations of the protester during infancy were respiratory abnormalities and developmental retardation.The brain magnetic resonance imaging (MRI) showed a " molar sign" , which was consistent with the diagnosis of Joubert syndrome.Genetic testing suggested that the protestor carried complex heterozygous variations of KIAA0586 gene.Two variants were not reported previously, one of which was synonymous mutation.The child is the first case of Joubert syndrome caused by KIAA0586 gene in China.Joubert syndrome is a rare congenital brain development malformation characterized by high clinical heterogeneity and MRI molar signs.It may involve multiple systems.Early identification and intervention can improve outcomes.

Changes in hematological parameters of long-term high-frequency platelet donors / 中国输血杂志

【Objective】 To understand the effect of long-term high-frequency platelet donation on the health, safety and platelet quality of blood donors. 【Methods】 From August 2020 to July 2022, blood donors who donated platelets for single collection in the station were selected as two groups: those who donated for 20-29 times and those who donated for 30-44 times. Such 14 test indexes as red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), platelet count (Plt), white blood cell count (WBC), large platelet ratio (P-LCR), lymphocyte (LYM) , neutrophil (NE), mean hemoglobin content (MCH), mean hemoglobin concentration (MCHC), platelet specific volume (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) were grouped and statistically analyzed for 5 times in each group. In addition, blood donors who have donated platelets more than 100 times in the station were chosen; the changes of their 5 parameters as RBC, Hb, Hct, PLT and WBC, as well as the correlation with the total number of platelet donations were analyzed through statistical analysis of the first 100 donations(10 donations/group). 【Results】 During 2 years, the hematological parameters were similar between 20-29 donation group(n=30) and 30-44 donation group(n=11) (P>0.05). For donors with donations≥100 occasions, RBC, Hb, Hct and WBC were negatively correlated with the number of blood donations, while Plt was positively correlated. There were significant differences in Hb, Hct, WBC and Plt among groups (P<0.05). Hb, Hct and WBC showed a downward trend, while Plt showed an upward trend. 【Conclusion】 With the increase of blood donations and units of blood donated, some changes in hematological parameters are observed among long-term high-frequency platelet donors. Monitoring and health education should be strengthened to ensure the safety and quality of blood donors.

Study on antioxidation and inhibiting melanin production of tetrahydrocurcumin and its mechanism / 中国药理学通报

Aim To evaluate the antioxidant effect of tetrahydrocurcuminoids(THC)and its effect on melanin production,and to explore its mechanism of inhibiting melanin production.Methods Human immortalized epidermal cell(HaCaT cell)model was used to evaluate the antioxidant activity.The activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-PX)and lactate dehydrogenase(LDH)in HaCaT cells were detected by ELISA.Total antioxidant activity of THC was detected by DPPH and T-AOC methods.Mouse melanoma cell model B16F10 was used on the experiment of inhibition of melanin production.The effect of THC on the proliferation activity of mouse B16F10 cells was determined by CCK8 assay.The content of melanin and tyrosinase activity in B16F10 cells were determined by NaOH lysis assay and dopamine oxidation assay,respectively.The effect of THC on B16F10 cell migration was investigated by scratch assay,and the expression of melanin production-related protein MITF was determined by Western blot.Results THC could increase the levels of SOD and GSH-Px in HaCaT cells,reduce the content of LDH,and increase the scavenging rate of DPPH free radical and the reducing ability of Fe3+.THC could inhibit the proliferation and migration of mouse B16F10 cells,reduce the content of melanin in B16F10 cells,reduce the activity of tyrosinase,and inhibit the expression of MITF.Conclusions Tetrahydrocurcumin has antioxidant effect and can inhibit melanin production,and its mechanism is related to inhibiting MITF expression.

Effect of Tibetan medicine E-se on insulin resistance in KK-Ay mice with spontaneous type 2 diabetes / 中国药理学通报

Aim To evaluate the effect of E-se extract on insulin resistance in KK-Ay mice with spontaneous type 2 diabetes anrl explore its mechanism.Methods Ten C57/6J mice were assigned to a normal control group.Fifty KK-Ay model mice were randomly divided into model group, positive control group ( rosiglita- zone, 2.67 mg • kg 1 ), and low- ( 0.75 g • kg 1 ) , medium- ( 1.50 g • kg 1 ) , and high-dose ( 3.00 g • kg ') E-se groups, with 10 mice in each group.All mice were measured for body weight and fasting blood glucose weekly, insulin tolerance on the 32nd day, and insulin after the last administration on the 35th day, and the insulin resistance/sensitivity indexes were calculated.The pancreas was stained by hematoxylin- eosin ( HE ).Islet cell apoptosis was detected by TUNEL staining.Glucagon-like peptide-1 ( GLP-1 ) was detected by immunohistochemistry.Results j j Compared with the model group, the E-se groups showed reduced body weight, fasting blood glucose, serum insulin concentration, and insulin resistance in¬dex, elevated insulin sensitivity index, decreased le¬sion grading score of pancreatic tissues and apoptosis percentage of islet cells, and increased content of GLP- 1 protein in pancreatic tissues.Conclusions E-se ex¬tract can improve insulin resistance by reducing serum insulin level, inhibiting islet cell apoptosis, and in¬creasing the sensitivity of the body to insulin.