[Single-cell transcriptomic sequencing coupled with Mendelian randomization analysis elucidates the pivotal role of CTSC in chronic rhinosinusitis].

Objective: To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs. Methods: Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing. Results: An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes (CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC+cells in CRS. Conclusion: This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.

[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

[Clinical and prognostic analysis of opsoclonus-myoclonus-ataxia syndrome in children].

Objective: To summarize the clinical and prognostic features of children with opsoclonus-myoclonus-ataxia syndrome (OMAS). Methods: A total of 46 patients who met the diagnostic criteria of OMAS in the Department of Neurology, Beijing Children's Hospital from June 2015 to June 2023 were retrospectively analyzed. Centralized online consultations or telephone visits were conducted between June and August 2023. The data of the children during hospitalization and follow-up were collected, including clinical manifestations, assistant examination, treatment and prognosis. According to the presence or absence of tumor, the patients were divided into two groups. The chi-square test or Mann-Whitney U test was used to compare the differences between the two groups. Univariate Logistic regression was used to analyze the factors related to OMAS recurrence and prognosis. Results: There were 46 patients, with 25 males and the onset age of 1.5 (1.2, 2.4) years. Twenty-six (57%) patients were diagnosed with neuroblastoma during the course of the disease, and no patients were categorized into the high-risk group. A total of 36 patients (78%) were followed up for≥6 months, and all of them were treated with first-line therapy with glucocorticoids, gammaglobulin and (or) adrenocorticotrophic hormone. Among the 36 patients, 9 patients (25%) were treated with second-line therapy for ≥3 months, including rituximab or cyclophosphamide, and 17 patients (47%) received chemotherapy related to neuroblastoma. At the follow-up time of 4.2 (2.2, 5.5) years, 10 patients (28%) had relapsed of OMAS. The Mitchell and Pike OMS rating scale score at the final follow-up was 0.5 (0, 2.0). Seven patients (19%) were mildly cognitively behind their peers and 6 patients (17%) were severely behind. Only 1 patient had tumor recurrence during follow-up. The history of vaccination or infection before onset was more common in the non-tumor group than in the tumor group (55%(11/20) vs. 23%(6/26), χ²=4.95, P=0.026). Myoclonus occurred more frequently in the non-tumor group (40%(8/20) vs. 4%(1/26), χ²=7.23, P=0.007) as the onset symptom. Univariate Logistic regression analysis showed that the tumor group had less recurrence (OR=0.19 (0.04-0.93), P=0.041). The use of second-line therapy or chemotherapy within 6 months of the disease course had a better prognosis (OR=11.64 (1.27-106.72), P=0.030). Conclusions: OMAS in children mostly starts in early childhood, and about half are combined with neuroblastoma. Neuroblastoma in combination with OMAS usually has a low risk classification and good prognosis. When comparing patients with OMAS with and without tumors, the latter have a more common infection or vaccination triggers, and myoclonus, as the onset symptom, is more common. Early addition of second-line therapy is associated with better prognosis in OMAS.

Interaction between handgrip strength and vitamin D deficiency on all-cause mortality in community-dwelling older adults: a prospective cohort study.

OBJECTIVE: Muscle strength decline and vitamin D deficiency are coexisting conditions associated with multiple adverse health outcomes. This prospective study aimed to investigate the multiplicative and additive interactions between handgrip strength (HS) and serum 25-hydroxyvitamin D [25(OH)D] on all-cause mortality in Chinese community-dwelling older adults. STUDY DESIGN: This is a population-based cohort study. METHODS: 2635 older adults (85.15 ± 12.01 years) were recruited from the Chinese Longitudinal Healthy Longevity Survey (2012-2018). Low HS was defined according to the Asian Working Group for Sarcopenia 2019 updated consensus (<28 kg for men and <18 kg for women). Serum 25(OH)D < 50 nmol/L were defined as vitamin D deficiency. Cox proportional hazard models were used to examine the association of HS and 25(OH)D with all-cause mortality. Socio-demographics, health status, and clinical characteristics were included as covariates. RESULTS: 1715 (65.09 %) and 1885 (71.54 %) participants had low HS and vitamin D deficiency, respectively. During a median follow-up of 3.52 years, 1107 older people died. After multivariable adjustment, both HS and 25(OH)D levels were inversely associated with all-cause mortality risk (Ps < 0.001). The hazard ratios (HRs) of low HS and vitamin D deficiency for all-cause mortality were 1.73 (95 % CI: 1.41-2.13) and 1.61 (95 % CI: 1.32-1.93), respectively. Although significant multiplicative interactions were not found, the association between low HS and all-cause mortality was attenuated in the higher 25(OH)D subgroup than in the lower 25(OH)D subgroup (stratified by 50 nmol/L). The multiple-adjusted HR of mortality for combined low HS and vitamin D deficiency was 2.18 (95 % CI: 1.73-2.56), which was higher than that for these two conditions alone. Significant additive interactions between low HS and vitamin D deficiency on mortality were observed (relative excess risk due to interaction: 0.71, 95 % CI: 0.37-1.05). CONCLUSIONS: Low HS and low 25(OH)D levels synergistically increased the risk of all-cause mortality. Our results added new insights to the priority of early detection for older adults with comorbid muscle strength decline and vitamin D deficiency.

[Clinical value of mesh prophylaxis for parastomal hernia based on evidence-based medicine].

The incidence of parastomal hernia is substantially high, significantly affecting the quality of life of patients with stoma. How to effectively solve the problem of parastomal hernia is a long-term focus of hernia and abdominal wall surgery and colorectal surgery. The European Hernia Society guidelines on prevention and treatment of parastomal hernia published in 2018 has recommended the use of a prophylactic mesh to prevent parastomal hernia for the first time. In the following 5 years, more randomized controlled trials of multi-center, large-sample, double-blind, long-term follow-up have been published, and no significant effect of mesh prophylaxis has been observed on the incidence of parastomal hernia. However, whether mesh could decrease surgical intervention by limiting the symptoms of parastomal hernias would become a potential value of prophylaxis, which requires further research to elucidate.

[Analysis of clinical and imaging features of 6 cases of linear scleroderma en coup de sabre with central nervous system involvement in children].

Objective: To summarize the clinical and imaging features of linear scleroderma en coup de saber (LSCS) with central nervous system involvement in children. Methods: The clinical data(clinical manifestations and imaging features) of 6 children diagnosed with LSCS with central nervous system involvement who were admitted to Beijing Children's Hospital Affiliated to Capital Medical University from May 2019 to November 2021 were retrospectively analyzed. Results: The 6 patients were all female, aged 6.8 (3.3, 11.0) years at the time of diagnosis, and aged 3.0 (1.7, 4.1) years at the time of discovery of facial skin lesions. Facial skin lesions appeared before neurological symptoms in 5 cases, and neurological symptoms appeared 2 months before skin lesions in 1 case. All the patients had "sword wound" skin lesions on the forehead with alopecia. Neurological manifestations included epileptic seizures in 6 cases, focal neurological defects in 5 cases, and headaches in 2 cases. The intracranial lesions were all ipsilateral to the skin lesions. The magnetic resonance imaging (MRI) of 6 cases showed abnormal signals mainly involving white matter in 1 hemisphere, and 3 cases showed local encephalomalacia. The scattered low signal was observed in 5 cases on susceptibility weighted imaging. Localized brain parenchyma or leptomeninges enhancement was seen on Gadolinium-enhanced sequences in 5 cases. Scattered foci of calcification on the affected side were seen on cranial CT in 4 cases. Skin biopsy was performed in 2 cases. Part of the lesion of the brain was removed in 1 case, and the pathological findings suggested small vasculitis, which was consistent with skin pathological changes. All patients received symptomatic treatment with antiepileptic drugs. Oral prednisone combined with methotrexate was given in 4 cases, and 1 case was given oral prednisone only. One case was presumed to be in the resting stage of the disease due to significant cerebral atrophy in half of the brain, and only antiepileptic drugs were added. The patients were followed up for 6-36 months. The skin lesions of scleroderma and alopecia did not progress in 5 cases, and hemifacial atrophy was developed in 1 case, which was considered to be combined with Parry-Romberg syndrome. The seizures were controlled in 4 cases. One case had reduced seizure frequency but left hemiplegia. One patient still had intractable epilepsy and paroxysmal headache. Conclusions: LSCS with central nervous system involvement is more common in girls, with seizures and neurological defects as the main manifestations. Intracranial lesions are mostly ipsilateral to the skin lesions. Cerebral microbleeds, calcification, and encephalomalacia foci are common, and the pathological changes in skin and intracranial lesions are consistent with small-vessel vasculitis. Prednisone combined with methotrexate treatment has shown some efficacy, but some children remain with refractory epilepsy and neurological deficit symptoms.

[Analysis of the etiology and clinical characteristics of patients with hemophagocytic lymphohistiocytosis].

Objective: To explore the etiology of hemophagocytic lymphohistiocytosis (HLH) and analyze the clinical features, treatment options and outcomes of patients with HLH induced by infectious and non-infectious factors. Methods: The clinical data of 97 patients aged ≥14 years who were diagnosed or suspected of HLH during their hospitalization at Peking University First Hospital from January 1, 2006 to December 4, 2021 were retrospectively analyzed, and 80 patients with HLH were further screened for inclusion. The general condition and etiological composition of the patients were analyzed, and the laboratory tests, treatment and outcome of patients in the infection, tumor and autoimmune disease groups were compared. Results: The age[M(Q1,Q3)] of the 80 patients with HLH was 53.5 (32.0, 64.0) years, with a male-to-female ratio of 1∶1. Of the 80 HLH patients with HLH, 23.8% (19/80)、37.5% (30/80)、15.0% (12/80)、10.0% (8/80) were secondary to infection, neoplasm, autoimmune disease, and mixed factors, respectively, with EBV infection (n=15) and hematologic neoplasm (n=28) being the most common etiologies in infection or non-infection-related HLH. The incidence of peripheral blood secondary or tertiary lineage reduction was significantly higher in patients in the infection group than in the autoimmune disease group [68.4% (13/19), 33.3% (4/12), P=0.002]. Serum ferritin (SF) ≥500 µg/L and ≥1 500 µg/L were 93.1% (54/58) and 72.4% (42/58), respectively; among them, 29 patients had significantly lower SF after treatment than before treatment, 1 049 (362, 1 769)µg/L and 2010 (1 231, 7 323) µg/L (P<0.001). Phagocytosis was seen in 68.75% (55/80) and HLH-related gene mutations were detectable in 5 cases. In the three groups, 13.1% (8/61) of patients died of disease, 47.5% (29/61) improved and 9.8% (6/61) relapsed. Conclusions: HLH has no specific symptoms and progresses rapidly, mainly due to infections, neoplastic diseases, autoimmune diseases. The prognosis may be improved with early treatment.

[Efficacy observation of the caudal-medial approach combined with "page-turning" middle lymphadenectomy in the laparoscopic right hemicolectomy].

Objective: To investigate the safety and feasibility of caudal-medial approach combined with "page-turning" middle lymphadenectomy in the laparoscopic right hemicolectomy. Methods: A descriptive cohort study was conducted. Clinical data of 35 patients who underwent laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy at Department of Gastrointestinal Surgery, Guangdong Hospital of Chinese Medicine from April 2018 to May 2020 were retrospectively analyzed. All operations were performed consecutively by the same surgeon. The caudal-medial approach was used to dissect the right Toldt's fascia and the anterior pancreaticoduodenal space in a caudal-to-cranial and medial-to-lateral manner guided by the duodenum. The "page-turning" middle lymphadenectomy was used to dissect the mesocolon along the superior mesenteric vein with ileocolic vein, Henle's trunk and pancreas exposed preferentially. Results: All the 35 patients completed the operation successfully, and there was no damage and bleeding of superior mesenteric vessels and their branches. The operative time was (186.9±46.2) minutes, and the blood loss was 50 (10-200) ml. The first time to flatus was (2.1±0.6) days, and the time to fluid intake was (2.5±0.8) days. The postoperative hospital stay was 6 (3-18) d. The overall morbidity of postoperative complication was 8.6% (3/35), including grade II in 1 cases (2.8%) and grade IIIa in 2 case (5.7%) according to the Clavien-Dindo grading standard. The total number of lymph node dissected was 30.2±5.6, and the positive lymph node was 0 (0-7). Tumor staging revealed 5 cases of stage I, 18 cases of stage II, 11 cases of stage III, and 1 case of stage IVA. In this study, the median follow-up time was 15 (4-29) months. One patient died due to cerebrovascular accident 12 months after surgery, and no tumor recurrence or metastasis was observed in all other patients. Conclusions: Laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy is safe and feasible. The anterior pancreaticoduodenal space is preferentially mobilized, which reduces the difficulty of central vascular dissection.

[Effect of platelet reactivity on clinical events in patients using bivalirudin in selective percutaneous coronary intervention].

Objective: To investigate the effect of platelet reactivity and other clinical factors on the postoperative 1-year adverse clinical events in patients who underwent selective percutaneous coronary intervention (PCI) anticoagulated with bivalirudin. Methods: This is a multicenter, retrospective and observational study, enrolling 632 patients at high risk of bleeding adjudicated by operators who underwent selective PCI anticoagulated with bivalirudin and had preoperative thrombelastography (TEG) test results in Fuwai Hospital, Northern Theater General Hospital and Xinxiang Central Hospital between January 2017 and August 2018. Platelet reactivity was tested by TEG and adenosine-induced maximal amplitude (MAADP) was recorded. According to MAADP patients were divided into three groups: low on-treatment platelet reactivity (LTPR) group (MAADP<31 mm, n=229), normal on-treatment platelet reactivity (NTPR) group (31 mm≤MAADP≤47 mm, n=207) and high on-treatment platelet reactivity (HTPR) group (MAADP>47 mm, n=196). The endpoints consisted of major adverse cardiovascular and cerebrovascular events (MACCE) and bleeding events. The definition of MACCE was the composite of all-cause mortality, myocardial infarction, intrastent thrombosis, stroke and revascularization. Bleeding events were defined by bleeding academic research consortium (BARC) type 2, 3 and 5 bleeding. Using multivariate Cox regression to analyze the factors of MACCE and bleeding events in patients underwent selective PCI anticoagulated with bivalirudin. Results: A total of 632 patients were finally enrolled in the study with age of (68.3±10.0) years and there were 423 (66.9%) males. All of 632 patients finished one-year follow-up, and 48 (7.6%) patients occurred MACCE and 11 (1.7%) patients occurred bleeding events. There was not statistically significant difference in the incidence of MACCE (8.3% (19/229) vs. 6.3% (13/207) vs.8.2% (16/196), P=0.68) and bleeding events (1.8% (4/229) vs. 2.9% (6/207) vs. 0.5% (1/196), P=0.17) in LTPR, NTPR and HTPR group. Multivariate Cox regression showed that HTPR was not the independent factor of MACCE (HR=1.25, 95%CI 0.67-2.30, P=0.49), and the history of peripheral vessel disease was the independent risk factor of MACCE (HR=2.47, 95%CI 1.19-5.11, P=0.02). LTPR was not the independent factor of bleeding events (HR=1.35, 95%CI 0.39-4.66, P=0.64), and the independent factors of bleeding events were history of peripheral vessel disease (HR=3.95, 95%CI 1.03-15.22, P=0.05) and hemoglobin (HR=0.96, 95%CI 0.93-0.99, P=0.01). Conclusions: In patients undergoing selective PCI anticoagulated with bivalirudin, there is no significant association between platelet reactivity and postoperative 1-year MACCE or bleeding events. History of peripheral vessel disease is an independent risk factor of MACCE, and history of peripheral vessel disease and decreased hemoglobin are independent risk factors of bleeding events.

[Application of membrane anatomy theory in totally extraperitoneal inguinal hernia repair].

Trocar placement and camera-dissection in the midline is the most commonly applied method for total extraperitoneal inguinal hernia repair (TEP), for which the theory of membrane anatomy has guiding significance. We hereby applies the theories and concepts, such as "fascia lining", "multi-layer", "inter-fascial planes", "combined inter-fascial plane" and "plane transition", to elucidate the key steps of TEP, for instance, space creation, hernia sac dissection, mesh flattening. Camera-dissection is performed along the posterior sheath of the rectus abdominis. Firstly, the camera enters retro-rectus space locating between the rectus abdominis and the transversalis fascia (TF). There are inferior epigastric vessels and their branches in the retro-rectus space, thus over-dissection should be avoided. Secondly, the camera goes downward through the TF into the pre-peritoneal space. The pre-peritoneal space is divided into the parietal plane and visceral plane by pre-peritoneal fascia (PPF). Both bladder and spermatic cord components locate on the visceral plane. Dissection of the median area should be implemented on the parietal plane, namely "surgical space", to protect the bladder. The parietal plane is the "holy plane" of TEP. Dissection of the indirect hernia area should be implemented on the visceral plane, namely "anatomical space", to protect the spermatic cord components. The reduction of direct hernia could be understood as the easy separation of TF and PPF. The reduction of indirect hernia is relatively difficult separation of peritoneum and spermatic cord components. During the transition of parietal and visceral planes, PPF (especially the pre-peritoneal loop) should be dissected for complete parietalization, in order to flatten the mesh.

[Clinical observation on the overlapping syndrome of myelin oligodendrocyte glycoprotein antibody and anti-N-methyl-D aspartate receptor in children].

Objective: To investigate the clinical features, imaging findings and prognosis of children with overlapping syndrome of myelin oligodendrocyte glycoprotein (MOG) antibody disease and anti-N-methyl-D aspartate receptor (NMDAR) encephalitis (MNOS). Methods: The clinical manifestations, immunological antibodies in blood and cerebrospinal fluid, cranial image, treatment and follow-up of 11 patients diagnosed as MNOS in the Department of Neurology, Beijing Children's Hospital from January 2011 to April 2019 were analyzed retrospectively. Results: A total of 11 patients, including 4 males and 7 females were analyzed, the age of onset was (10.4±2.3) years. A total of 29 episodes occurred in 11 children. At the last follow-up, 8 cases showed relapsed remission course, the interval of recurrence was 3 to 60 months. The onset symptoms of 11 patients included convulsions (10 cases), lethargy (6 cases), psychosis (6 cases). Among 29 episodes, the common symptoms were convulsions (16 episodes), psychosis (13 episodes),and lethargy (10 episodes). According to the diagnostic criteria of anti-NMDAR encephalitis and MOG-antibody disease, 29 episodes were divided into three phenotypes, including anti-NMDAR encephalitis(4 episodes), MOG-antibody diseases (10 episodes) and overlapping types (15 episodes).Twenty-seven times of acute stage cranial magnetic resonance imaging (MRI) were available, common lesions included cortical focus (22 times), subcortical white matter (7 times), brainstem (9 times). All patients were sensitive to first-line immunotherapy. Eight patients had recurrence during glucocorticoid reduction, 6 of them were treated with additional second-line immunosuppressive therapy, including cyclophosphamide (1 case) and mycophenolate mofetil (5 cases). The follow-up time of patients were 5-99 months. At the last follow-up, all patients were in remission, the pediatric cerebral performance category (PCPC) score was 1 (10 cases) and 2 (1 cases). Conclusions: MNOS mainly affects older children. In the period of acute episodes, convulsions and psychosis are common. The cranial MRI showed extensive brain involvement and mainly in the cortex. The recurrence rates of MNOS are relatively high, patients are sensitive to first-line immunotherapy. No significant neurological dysfunction was left in the remission stage.

CircRNA_002178 promotes the proliferation and migration of oral squamous cell carcinoma cells by activating the Akt/mTOR pathway.

OBJECTIVE: We aimed to investigate the biological effects of circRNA_002178 in oral squamous cell carcinoma (OSCC) tissues and to analyze its potential mechanism. PATIENTS AND METHODS: CircRNA_002178 expression in 50 pairs of OSCC tissues and adjacent ones was studied by quantitative polymerase chain reaction (qPCR) analysis, and the correlations of circRNA_002178 with clinicopathological indicators, as wells as prognosis of OSCC patients were analyzed. qPCR was used to verify circRNA_002178 expression in OSCC cell lines. Subsequently, circRNA_002178 knockdown models were constructed using lentivirus in OSCC cell lines, and the impacts of circRNA_002178 on the function of OSCC cells were assessed by cell counting kit-8 (CCK-8) test, plate cloning experiment, transwell assay and nude mouse tumor formation experiments. Finally, rescue experiments in vitro were used to explore the potential mechanism of circRNA_002178 activating Akt/mTOR pathway. RESULTS: Our data showed that circRNA_002178 expression in OSCC tissue specimens was remarkably higher than that in adjacent ones. In comparison to patients in low circRNA_002178 expression group, patients in high expression group showed higher incidences of advanced pathological stage and distant metastasis, and a lower overall survival rate. Cell functional experiments revealed that knockdown of circRNA_002178 markedly attenuated the proliferation and migration ability of OSCC cells compared to the sh-NC group, and the consistent results were observed in the nude mouse experiment. In addition, Western blot suggested that the expression of key proteins in Akt/mTOR signaling pathway was remarkably reduced after downregulation of circRNA_002178 in OSCC cells. Meanwhile, Akt activator SC79 reversed the inhibitory effect of circRNA_002178 on the metastasis and proliferation of OSCC cells. CONCLUSIONS: CircRNA_002178, over-expressed in OSCC tissues and cell lines, may promote the malignant progression of OSCC through activating the Akt/mTOR signaling pathway.

[Influence on physical development of children aged 18 months from HIV-positive mothers for prevention mother to child transmission of HIV].

Objective: To explore influence on physical development of children aged 18 months from HIV-positive mothers for prevention mother to child transmission of HIV (PMTCT) in Guangxi Zhuang autonomous region, and provide evidence for the improvement PMTCT program. Methods: This retrospective case control study was conducted in 554 HIV negative infants aged 18 months whose HIV positive mothers had received PMTCT services reported through PMTCT system database from January 1, 2010 to December 31, 2017 and 1 109 healthy infants born in 2017, whose mothers were healthy, in Lingshan, Luzhai, and Hengxian counties, ranking top three counties with high HIV infection prevalence, in Guangxi. PMTCT data and physical development data such as height, weight and head circumference of children aged 18 months were collected. The physical dysplasia in the infants was defined as at least one of the three main indicators of height, weight and head circumference below the normal range. Results: The number of HIV-positive mother and their infants in the case group were 667 and 554 respectively, and the PMTCT rates were 91.15% (608/667) and 96.57% (535/554) respectively. HIV positive rate, mortality rate and mother to child transmission rate of the infants aged 18 months were 1.44% (8/554), 3.07% (17/554) and 1.91% (8/418) respectively, and the physical examination results of the infants aged 18 months showed that the physical dysplasia rate was 30.51% (169/554). Among the 1 109 infants in the control group, the physical dysplasia rate was 9.83% (109/1 109). The difference between the case group and the control group was significant (P<0.01). Conclusion: The PMTCT rates of HIV positive mother and their children were more than 90.00%, respectively. However, poor physical development rate of infants aged 18 months were more than 30.00%. The possible influence of PMTCT on physical development of the infants aged 18 months of HIV positive mother's needs to be further studied.

LncRNA MEG3 inhibits proliferation and promotes apoptosis of osteosarcoma cells through regulating Notch signaling pathway.

OBJECTIVE: To explore the effect of long non-coding ribonucleic acid (lncRNA)-maternally expressed gene 3 (MEG3) on the Notch signaling pathway, and its influences on the proliferation and apoptosis of osteosarcoma MG-63 cells. MATERIALS AND METHODS: LncRNA MEG3 was overexpressed in osteosarcoma MG-63 cells, and the cells were divided into Blank group, Len-con group, and Len-MEG3 group. The expression level of MEG3 in each group was detected via quantitative Polymerase Chain Reaction (qPCR), the cell proliferation level in each group was detected via Cell Counting Kit-8 (CCK-8) assay, and the apoptosis in each group was detected via Hoechst 33258 staining. Moreover, the content of the inflammatory factors in each group was determined using the Enzyme-Linked Immunosorbent Assay (ELISA), and the expression levels of apoptosis-related proteins and Notch signaling pathway-related proteins were determined through Western blotting. RESULTS: The expression level of lncRNA MEG3 in Len-MEG3 group was significantly higher than that in the Blank group and Len-con group (p<0.01). The overexpression of lncRNA MEG3 could significantly weaken the proliferation (p<0.01) and enhance the apoptosis of osteosarcoma cells (p<0.01). The overexpression of lncRNA MEG3 could significantly increase the content of the inflammatory factor interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) (p<0.01), and remarkably decrease the content of the anti-inflammatory factor IL-10 in osteosarcoma cells (p<0.01). Besides, the overexpression of lncRNA MEG3 could evidently raise the expression of Caspase3 (p<0.01) and reduce the Bcl-2/Bax expression in osteosarcoma cells (p<0.01). Finally, the overexpression of lncRNA MEG3 could remarkably reduce the protein expressions of Jagged1, Notch1, and NICD1 in osteosarcoma cells (p<0.01). CONCLUSIONS: The overexpression of lncRNA MEG3 can inhibit the proliferation and promote the apoptosis of osteosarcoma MG-63 cells by suppressing the Notch signaling pathway.

MicroRNA-424-5p inhibits the development of non-small cell LCa by binding to ITGB1.

OBJECTIVE: The aim of this study was to explore the effect of microRNA-424-5p on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells, and to investigate its influence on the expression of ITGB1 and potential regulatory mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the level of microRNA-424-5p in 44 paired NSCLC tissues and adjacent tissues. The relation between microRNA-424-5p expression and NSCLC clinical indicators was analyzed. Subsequently, microRNA-424-5p mimics and inhibitors were transfected into NSCLC cells to construct microRNA-424-5p overexpression or knockdown models, respectively. QRT-PCR was used to further verify the transfection efficiency. A series of experiments, including cell counting kit-8 (CCK-8) assay, colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), and flow cytometry were used to analyze the effect of microRNA-424-5p on the biological function of NSCLC A549 and H358 cells. Finally, the potential association between microRNA-424-5p and its downstream gene ITGB1 was explored through luciferase reporter gene assay and cell recovery experiment. RESULTS: QRT-PCR results showed that microRNA-424-5p level was significantly lower in NSCLC tissues than that of adjacent normal tissues. Compared with patients with high expression of microRNA-424-5p, the pathological stage of those with low expression of microRNA-424-5p was significantly higher. In vitro experiments showed that microRNA-424-5p overexpression remarkably decreased cell proliferation and increased cell apoptosis, which were further validated in microRNA-424-5p inhibitor group. Subsequently, ITGB1 expression was found significantly up-regulated in NSCLC cell lines and tissues. Meanwhile, ITGB1 expression was negatively correlated with microRNA-424-5p level. In addition, a recovery experiment indicated that overexpression of ITGB1 could counteract the effect of microRNA-424-5p mimics on the proliferation and apoptosis of NSCLC cells. All these findings revealed that microRNA-424-5p and ITGB1 affected the malignant progression of NSCLC. CONCLUSIONS: MicroRNA-424-5p was closely correlated with the pathological stage and poor prognosis of NSCLC, thereby inhibiting the occurrence and development of NSCLC.

[Analysis of clinical characteristics of 854 patients with thyroid cancer].

Objective:The aim of this study is to summarize and analyze the clinical features of thyroid cancer surgery patients, and provide information and guidance for clinical diagnosis and treatment. Method:The medical records of 854 patients with thyroid cancer who met the inclusion criteria from January 2013 to December 2018 were collected from the hospital's medical record system. Patients were grouped by age group and their stratified studies were performed on age, gender, pathological type, and cervical lymph node metastasis. Result:The total number of patients with thyroid cancer surgery in 2013-2018 showed an increasing trend. There was no significant difference in the age composition of thyroid cancer patients between different years （P>0.05）, but the age of 20-54 years old gradually increased with age, and reached a peak at 50-54 years old, then gradually decreased. There was no significant difference in gender composition between patients with thyroid cancer surgery in 2013-2018 （P>0.05）, but in 40-44 years old, the prevalence of women in the 50-54 age group was higher than that in men （P<0.05）, The prevalence of men in the 70-74 age group was higher than that in women （P<0.05）, and the peak period of both was 50-54 years old. Papillary carcinoma accounted for a high proportion （96.8%） in the pathological types of thyroid cancer surgery patients in 2013-2018, and the incidence of women in the 40-44 age group was higher than that in men（P<0.01）, in the 70-74 age range. The incidence was higher than that of women （P<0.01）. The incidence of follicular carcinoma （1%） was higher in men than in women （P<0.05）. The incidence of lymph node metastasis in women with thyroid cancer was lower than that in men （P<0.05）. Conclusion:The incidence of thyroid cancer in different age groups has its own characteristics, and prevention and control measures should be formulated according to age groups.

Evaluation of the readout electronics based on the center of gravity method for position sensitive radiation detection.

In the application of position sensitive radiation detection, the center of gravity method is often used to obtain better spatial resolution. In order to obtain the resolution degradation caused by the readout electronics, an evaluation method is put forward in this paper. The principle of the method is to simulate the signal distribution on sense wires of the MWPC (Multiwire Proportional Chamber) detector. The evaluation software quantizes the simulated data and drives the digital to analog converter to generate test signals. The readout electronics is evaluated with these stimulus signals according to the readout scale. An evaluation board based on this method is implemented. Tests are carried out in the laboratory to evaluate a readout circuit for the MWPC detector. The position resolution contributed by the electronics is better than 15 µm when the swtiching frenquency of the switch array is 12.5 MHz. The test results proved that the evaluation method is correct and practical. It can greatly simplify the evaluation of the readout electronics.