Preliminary evaluation of the efficacy and safety of brimonidine for general anesthesia.

BACKGROUND: To determine the hypnotic and analgesic effects of brimonidine, and evaluate its efficacy and safety for general anesthesia. Potentiation of pentobarbital sleeping time following brimonidine administration was observed in mice, as was the analgesic activity of brimonidine. METHODS: The median effective dose (ED50) and lethal dose (LD50) of intraperitoneally injected brimonidine were determined in hypnotized mice. In addition, the LD50 of intravenously injected brimonidine, and ED50 of intravenously, intramuscularly, and intrarectally injected brimonidine in hypnotized rabbits were determined. Finally, the synergistic anesthetic effect of brimonidine and chloral hydrate was evaluated in rabbits. RESULTS: Intraperitoneal injection of 10 mg/kg brimonidine enhanced the hypnotic effect of a threshold dose of pentobarbital. Intraperitoneally injected brimonidine produced dose-related analgesic effects in mice. The ED50 of intraperitoneally administered brimonidine in hypnotized mice was 75.7 mg/kg and the LD50 was 379 mg/kg. ED50 values of intravenous, intramuscular, and intrarectal brimonidine for hypnosis in rabbits were 5.2 mg/kg, 8.8 mg/kg, and 8.7 mg/kg, respectively; the LD50 of intravenous brimonidine was 146 mg/kg. Combined intravenous administration of 0.6 mg/kg brimonidine and 0.03 g/kg chloral hydrate had a synergistic anesthetic effect. CONCLUSIONS: Brimonidine elicited hypnotic and analgesic effects after systemic administration and exhibited safety. Moreover, brimonidine enhanced the effects of other types of narcotics when combined.

Adipo-specific chemerin knockout alters the metabolomic profile of adipose tissue under normal and high-fat diet conditions: Application of an untargeted liquid chromatography-tandem mass spectrometry metabolomics method.

To explore the metabolic effect of chemerin, adipose-specific chemerin knockout (adipo-chemerin-/- ) male mice were established and fed with 5-week normal diet (ND) or high-fat diet (HFD), and then the glycolipid metabolism index was measured and epididymal adipose tissue metabolomics detected using untargeted LC-tandem mass spectrometry (LC-MS/MS). Under HFD, adipo-chemerin-/- mice showed improved glycolipid metabolism (decreased total cholesterol, low-density lipoprotein-cholesterol, insulin and Homeostasis Model Assessment of Insulin Resistance) compared with flox (control) mice. Furthermore, orthogonal partial least squares-discriminant analysis score plots identified separation of metabolites between adipo-chemerin-/- mice and flox mice fed ND and HFD. Under HFD, 28 metabolites were significantly enhanced in adipo-chemerin-/- mice, and pathway enrichment analysis suggested strong relationship of the differential metabolites with arginine and proline metabolism, phenylalanine metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis, which were directly or indirectly related to lipid metabolism, inflammation and oxidative stress. Under ND, taurine was increased in adipo-chemerin-/- mice, resulting in taurine and hypotaurine metabolism and primary bile acid biosynthesis. In conclusion, the improved effect of chemerin knockdown on the glycolipid metabolism of HFD-feeding male mice might be associated with the increases in differential metabolites and metabolic pathways involved in lipid metabolism, inflammation and oxidative stress, which provided insights into the mechanism of chemerin from a metabolomics aspect.

External application of traditional Chinese medicine in the treatment of bone cancer pain: a meta-analysis.

BACKGROUND: Bone cancer pain presents a clinical challenge with limitations of current treatments. Many patients seek additional therapies that may relieve pain. Many external applications of traditional Chinese medicines (EAs-TCMs) have been evaluated in clinical trials, but fewer are known about them outside of China. The objective of this study is to assess the efficacy for bone cancer pain. METHODS: A systematic literature search was conducted in seven databases until December 2014 to identify randomized controlled trials (RCTs) about EAs-TCMs in the treatment of bone cancer pain. The primary outcome was total pain relief rate. The secondary outcomes were adverse events at the end of treatment course. The methodological quality of RCTs was assessed independently using six-item criteria according to the Cochrane Collaboration. All data were analyzed using Review Manager 5.2.0. We included any RCTs evaluating an EA-TCM for the treatment of bone cancer pain. We conducted a meta-analysis. RESULTS: We included six RCTs with 534 patients. In general, the reporting of methodological issues was poor. Compared with morphine sulfate sustained release tablets (MSSRTs) or radiotherapy or bisphosphonates, we analyzed data from five trials reporting on complete response effect score (relative risk (RR) = 5.38, 95% confidence interval (CI) = 2.80-10.31, P < 0.00001) and partial response (RR = 1.18, 95% CI = 1.02-1.37, P = 0.02) and six trials reporting on total pain relief rate (RR = 1.49, 95% CI = 1.43-1.67, P < 0.00001). Six RCTs showed significant effects of EA-TCM for improving pain relief in patients with bone cancer pain. In addition, no severe adverse events were found. CONCLUSION: This systematic review showed positive but weak evidence of EA-TCM for bone cancer pain because of the poor methodological quality and the small quantity of the included trials. Future rigorously designed RCTs are required.

Gadoxetic acid disodium (Gd-EOBDTPA)-enhanced magnetic resonance imaging for the detection of hepatocellular carcinoma: a meta-analysis.

PURPOSE: To evaluate the diagnostic value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A systematic, comprehensive literature search was conducted in PubMed (2004 [Gd-EOB-DTPA was first approved in Europe in 2004] to April 2013), Embase (2004 to April 2013), Web of Science (2004 to April 2013), and the Cochrane Library (2004 to April 2013). The Quality Assessment of Diagnostic Studies (QUADAS) items was used to evaluate the quality of the included studies. Stata 12.0 was used to analyze the data. Pooled sensitivity (SEN), pooled specificity (SPE), pooled positive likelihood ratio (PLR), pooled negative likelihood ratio (NLR), pooled diagnostic odds ratio (dOR), and summary receiver operating characteristic (SROC) curves were calculated to assess the diagnostic value of the individual diagnostic tests. RESULTS: A total of 11 articles were included, involving 1578 nodules from four countries. The results of the meta-analysis showed that the pooled SEN, SPE, and SROC curve values were 0.92 (95% confidence interval [CI]: 0.89-0.94) 0.95 (95% CI: 0.93-0.97), and 0.98 (95% CI: 0.95-0.99), respectively, and subgroup analyses were performed. CONCLUSION: Gd-EOB-DTPA-enhanced MRI has value for the detection of HCC; in particular, it has high sensitivity for the detection of lesions larger than 10 mm.

Water isolation technique combined with contrast-enhanced ultrasound guided puncture biopsy of pancreatic mass in 3 cases.

In many patients with pancreatic cancer the definite pathological diagnosis is limited due to the lack of safe needle entry routes, the high risk of conventional ultrasound-guided puncture and the low positive rate of single needle. To solve the situations in which there are no safe path for pancreatic biopsy, we used water isolation technology combined with contrast-enhanced ultrasound to perform puncture biopsy in 3 patients with pancreatic mass occupying under the guidance of coaxial needle in this study and remarkable results were achieved. The water isolation technique was used to avoid the damage to theimportant organs in front of the occupying area.

Correlation between DKK1 promoter methylation level and diabetic microangiopathopathy complicated with osteoporosis / 中华内分泌外科杂志

Objective:To investigate the correlation between the promoter methylation level of Dickkopf-related protein 1 (DKK1) gene and diabetic microangiopaopathy complicated with osteoporosis.Methods:Patients with type 2 diabetes mellitus (T2DM) microangiopathopathy who were admitted to our hospital from Jan. 2019 to Dec. 2022 were collected as research objects, and divided into observation group (44 cases) and control group (58 cases) according to whether they were complicated with osteoporosis. Bone mineral density (BMD) of lumbar spine (L1-4) was measured, and bone metabolism indexes, including serum calcium, serum phosphorus, 25-hydroxy vitamin D3[25-hydroxy vitamin D3, 25- (OH) D3], PTH, C-terminal telopeptide of typeI collagen (CTX), procollagen of aminoterminal propeptide (PINP) and tartrate resistant acid phosphatase (TRACP) levels were detected; The promoter methylation level of DKK1 gene was determined.Results:The methylation level of DKK1 gene promoter in the observation group was 5.17%±0.73%, which was significantly higher than that in the control group (3.81%±0.61%), with statistical significance ( t=5.22, P<0.001). The 25- (OH) D3 level, PTH and lumbar bone density in the observation group were significantly lower than those in the control group, while the CTX and TRACP levels were significantly higher than those in the control group ( t was 5.58, 4.35, 4.12, 4.05 and 4.17, respectively, P<0.001). In all patients, the promoter methylation level of DKK1 gene was significantly positively correlated with CTX and TRACP ( r was 0.41 and 0.39, P was 0.006 and 0.027, respectively), and significantly negatively correlated with PTH and lumbar bone density ( r was -0.38 and -0.43, respectively). P=0.015 and 0.003, respectively). ROC curve analysis showed that the area under the curve of DKK1 methylation level to distinguish type 2 diabetes microangionopathy with and without osteoporosis was 0.841 (0.762-0.921), and the sensitivity and specificity were 86.4% and 72.4%, respectively. Conclusion:The methylation level of DKK1 gene promoter is associated with osteoporosis and bone metabolism in T2DM patients with microangiopathia.

Clinical characteristics of programmed cell death-1 inhibitor-associated hypophysitis / 中华内科杂志

Objective:To explore the clinical features of programmed cell death-1 (PD-1) inhibitor-associated hypophysitis and improve the understanding of the disease.Methods:For the present retrospective case series study, the clinical data of patients with PD-1 inhibitor-associated hypophysitis who were treated at the Affiliated Hospital of Hebei University and the 3rd Hospital of Hebei Medical University from January 2020 to May 2023 were collected for analysis of clinical manifestations and prognosis.Results:Fifteen cases of PD-1 inhibitor-induced hypophysitis were included, with 13 males and 2 females. The mean age of onset was (62.1±7.5) years, and the median time of onset was 6.5 (4.7, 11.6) cycles of PD-1 inhibitor. At diagnosis, 14 patients complained of gastrointestinal symptoms, and 12 patients complained of fatigue. There were 12, 1, 1, 5, and 1 cases of hyponatremia, hypokalemia, hypoglycemia, hypotension, and fever, respectively. Secondary adrenocortical insufficiency occurred in all cases. Moreover, four patients had secondary hypothyroidism, and two patients had secondary hypogonadism. Posterior pituitary hypofunction was not found. Pituitary MRI showed one case each of vacuolar sella turcica, pituitary cystic lesion, pituitary stalk slightly shifted to the left, high metabolism in the sella turcica, and pituitary abnormal signal, while no abnormalities were found in 11 cases. The follow-up time was (47.66±11.93) weeks. At the last follow-up, one patient′s serum levels of adrenocorticotropic hormone and cortisol returned to normal.Conclusions:Hypophysitis associated with PD-1 inhibitors occurs later, and gastrointestinal symptoms and fatigue are the most common clinical manifestations. PD-1 inhibitor-associated hypophysitis mainly manifests as adrenocortical hypofunction, and some cases manifest as hypothyroidism and hypogonadism. In addition, patients with PD-1 inhibitor-associated hypophysitis show no obvious imaging changes in the pituitary gland.

Role of heterotrimer G protein in podocyte injury / 中国临床药理学与治疗学

GPCRs are the largest membrane protein receptor superfamily in the human body, with more than 800 isoforms, and approximately 35% of Food and Drug Administration-approved and marketed drugs currently target GPCRs for the treatment of a wide range of diseases, for heart failure (beta-adrenergic receptors), peptic ulcer (histamine receptors), prostate cancer (gonadotropin receptors), hypertension (adrenergic and angiotensin receptors), pain (opioid receptors), and bronchial asthma (beta2-adrenergic receptors) examples. Although the number of GPCRs is enormous, the signaling proteins downstream of them are limited, heterotrimeric G proteins (GPs) are key proteins that signal GPCRs, translate extracellular stimuli into intracellular responses by coupling to GPCRs and initiate multiple signaling events via downstream cascades. Podocytes are an important component of the glomerular filtration barrier, and their damage is a central event in proteinuria formation and progressive glomerulosclerosis. This article reviews the regulation of GPs, their signaling and their role in podocyte injury to provide a theoretical basis for scientific research and clinical treatment of this disease.

Construction of a machine learning model for identifying clinical high-risk carotid plaques based on radiomics / 中国胸心血管外科临床杂志

@#Objective     To construct a radiomics model for identifying clinical high-risk carotid plaques. Methods     A retrospective analysis was conducted on patients with carotid artery stenosis in China-Japan Friendship Hospital from December 2016 to June 2022. The patients were classified as a clinical high-risk carotid plaque group and a clinical low-risk carotid plaque group according to the occurrence of stroke, transient ischemic attack and other cerebrovascular clinical symptoms within six months. Six machine learning models including eXtreme Gradient Boosting, support vector machine, Gaussian Naive Bayesian, logical regression, K-nearest neighbors and artificial neural network were established. We also constructed a joint predictive model combined with logistic regression analysis of clinical risk factors. Results    Finally 652 patients were collected, including 427 males and 225 females, with an average age of 68.2 years. The results showed that the prediction ability of eXtreme Gradient Boosting was the best among the six machine learning models, and the area under the curve (AUC) in validation dataset was 0.751. At the same time, the AUC of eXtreme Gradient Boosting joint prediction model established by clinical data and carotid artery imaging data validation dataset was 0.823. Conclusion     Radiomics features combined with clinical feature model can effectively identify clinical high-risk carotid plaques.

False-positive HIV-1 nucleic acid testing results in patients with severe thalassemia after receiving cell and gene therapy / 中华检验医学杂志

A 11-year old female patient with severe thalassemia, receipt a lentivirus-based cell and gene therapy (CGT) therapy in Shenzhen Children′s Hosptial on July 27th, 2021. At the two follow-up visits after discharge, patient were continuously tested positive for HIV screening through HIV Ag/Ab Combo assay (chemiluminescence Immunoassay), and the viral load results of HIV-1 nucleic acid testing (NAT) were both>5 000 copies/ml. The patient can be diagnosed with HIV infection according to the National Guideline for Detection of HIV/AIDS(2020 Revised Edition). The thorough investigation findings and supplementary experiment results indicated that the false-positive HIV-1 NAT results was caused by cross-reactivity between the target sites detected by conventional HIV-1 NAT reagents and the lentiviral vectors fragments integrated into the genome of patient′s hematopoietic stem/progenitor cells. In conclusion, it is important for laboratories to select appropriate HIV-1 NAT testing platforms which won′t cause cross-reactivity for the testing of samples from patients who have been treated with HIV-derived vectors. It is also recommended to design and develop NAT testing platforms with multiple target regions labeled by different fluorescents for HIV NAT supplementation experiment to reduce the risk of false-positive diagnoses of HIV infection.

Research progress of Nrf2 in ovarian cancer / 国际肿瘤学杂志

Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important transcription factor that regulates redox, lipid metabolism and protein dynamic balance, and plays an important role in protecting the body from oxidative stress damage. Recently, more and more studies have shown that Nrf2 is activated in ovarian cancer by various mechanisms to induce increased antioxidant enzymes, change sex hormone metabolism and induce downstream targets. Further studying the mechanism of Nrf2 in promoting the development of ovarian cancer, exploring its role in drug resistance and seeking new therapeutic targets can provide new ideas for the treatment of drug-resistant ovarian cancer.

Analysis of prevention and control results of three-year campaign for Kashin-Beck disease in Pingliang City, Gansu Province / 中华地方病学杂志

Objective:To learn about the current situation of prevention and control results of three-year campaign for Kashin-Beck disease (KBD) in Pingliang City, and to provide scientific basis for prevention and control of KBD.Methods:A retrospective analysis was carried out to collect the KBD surveillance data of all villages in the counties (cities, districts) affected by KBD in Pingliang City, Gansu Province during 2019 - 2020 from the "National Integrated Management System for Endemic Disease Prevention and Control (Three-year Campaign Action Management System)", including, the prevalence of children aged 7 to 12 years old, the implementation of prevention and control measures, and the case investigation, the establishment, management of health files and treatment of current patients.Results:Patients with KBD were distributed in 6 counties (cities, districts), 64 townships (towns), and 690 villages in Pingliang City, and all of them were seriously ill area. In 2019 and 2020, 40 537 and 41 053 children aged 7 to 12 years old were examined, respectively, and the clinical detection rate was 0.08% (31/40 537) and 0.03% (12/41 053), respectively; the X-ray detection rate was 0 in each year. In the dietary structure of residents in Pingliang City from 2018 to 2020, the consumption proportions of rice, flour and other diets was 15.03%, 76.63% and 8.34%, respectively, and the purchase proportion of staple food was 19.28%. From 2018 - 2020, 9 564 households and 36 282 people had been relocated from the affected areas, 4 831 children aged 7 to 12 years old had been raised in different places, 14.81% (420 914/2 842 939) of the original cultivated land had been converted to cash crops, 21.81%(620 045/2 842 939) of the original cultivated land had been converted from farmland to forest (grass), and 231 811 nutrition package for children aged 6 to 24 months had been given. A total of 6 269 KBD patients were investigated and registered, including 3 722 males and 2 547 females, with a gender ratio of 1.00 ∶ 0.68. The most clinical grading was grade Ⅰ, accounting for 78.00% (4 890/6 269), followed by grade Ⅱ (15.89%, 996/6 269) and grade Ⅲ (6.11%, 383/6 269); the age of onset was (64.57 ± 10.01) years old, ranging from 16 to 87 years old; most patients were over 50 years old, accounting for 86.57% (5 427/6 269). In 2019, 1 659 KBD patients were treated. The apparent efficiency, effective efficiency and ineffective efficiency were 25.38% (421 cases), 52.92% (878 cases) and 21.70% (360 cases), respectively. In 2020, 1 395 KBD patients were treated; the apparent efficiency, effective efficiency and ineffective efficiency were 19.50% (272 cases), 61.65% (860 cases) and 18.85% (263 cases), respectively.Conclusions:All villages in KBD area in Pingliang City have reached the elimination standard and achieved the elimination goal. We should continue to do a good job in the dynamic monitoring of the disease, strengthen the implementation of prevention and control measures and rehabilitation intervention for patients with KBD, and improve the quality of life of patients.

Efficacy comparison of percutaneous vertebroplasty in the treatment of osteoporotic lumbar compression fracture via the approach through midpoint transverse process-transition zone of articular process and the unilateral transpedicular approach / 中华创伤杂志

Objective:To compare the efficacy of percutaneous vertebroplasty (PVP) in the treatment of osteoporotic lumbar compression fracture (OLCF) via the approach through midpoint transverse process-transition zone of articular process and the unilateral transpedicular approach.Methods:A prospective cohort study was conducted to analyze the clinical data of 794 patients with OLCF treated in Honghui Hospital affiliated to Xi′an Jiaotong University School of Medicine from January 2017 to December 2019. The patients were divided into transitional-zone puncture group (400 patients, 400 vertebrae) and pedicle puncture group (394 patients, 394 vertebrae) according to the envelope method. The transitional-zone puncture group was treated with PVP via the approach through midpoint transverse process-transition zone of articular process, and the pedicle puncture group was treated with PVP via the unilateral transpedicular approach. The operation time and radiation dose were documented. The visual analogue score (VAS) and Oswestry dysfunction index (ODI) were evaluated before operation and at 1 day, 3 months, 1 year after operation. The cement distribution and the incidence of complications such as cement leakage, re-fracture of the injured vertebra, spinal cord nerve injury and facet joint injury were detected.Results:The patients were composed of 270 males and 524 females, at the age of 68.9-78.5 years [(73.7±4.8)years]. All patients were followed up for 12-14 months [(13.4±0.8)months]. The operation time and radiation dose in transitional-zone puncture group were reduced compared with pedicle puncture group ( P<0.01). There was no significant difference in VAS and ODI between the two groups before operation (all P>0.05). The VAS between transitional-zone puncture group [(2.1±0.9)points, (2.3±1.1)points, (2.7±1.3)points] and pedicle puncture group [(2.3±0.7)points, (2.5±0.9)points, (2.9±1.1)points] was obviously reduced from that before operation (all P<0.01), significantly different at 1 day, 3 months, 1 year after operation ( P<0.05 or 0.01). The ODI between transitional-zone puncture group (14.3±1.8, 13.6±3.4, 11.3±4.4) and pedicle puncture group (25.5±5.7, 20.7±6.3, 20.6±6.9) was significantly different at 1 day, 3 months, 1 year after operation (all P<0.01), and all were obviously reduced from that before operation (all P<0.01). With regard to the cement distribution, the number of bilaterally cemented vertebrae in transitional-zone puncture group (324) was more than that in pedicle puncture group (94) ( P<0.01). The incidence of cement leakage, re-fracture of the injured vertebra and facet joint injury was 8.25%(22/400), 0.00%(0/400) and 3.25%(13/400) in transitional-zone puncture group, significantly different from 20.81%(82/394), 2.03%(8/394) and 9.90%(39/394) in pedicle puncture group ( P<0.05 or 0.01). There was no significant difference in spinal cord nerve injury between the two groups ( P>0.05). Conclusion:For OLCF, PVP via the approach through the midpoint transverse process-transition zone of articular process and the unilateral transpedicular approach are both effective, but the former has advantages of shorter operation time, smaller radiation dose, greater dispersion of bone cement and lower incidence of cement leakage, re-fracture of the injured vertebra and facet joint injury.

Safety and effectiveness of Neuroform Atlas stent-assisted coiling in the endovascular treatment of intracranial aneurysms: a single-center observational study / 中华内科杂志

Objective:To investigate the safety and effectiveness of Neuroform Atlas stent-assisted coiling in the endovascular treatment of intracranial aneurysms.Methods:This was a retrospective, single-center observational study of 77 patients who underwent endovascular treatment of intracranial aneurysms using the Neuroform Atlas device at the Department of Neurology, People′s Liberation Army General Hospital from July 2020 to May 2022. There were 34 males and 43 females, with a median (range) age of 59 (23-81) years. The degree and effect of aneurysm embolization were evaluated by modified Raymond grading post procedure and after 6 months. Complications occurring during the perioperative period were recorded. Vaso computed tomography was performed immediately after the operation to assess stent opening and adherence. Digital subtraction angiography was performed 6 months after discharge and the aneurysm was classified as cured, stable, or recurrent.Results:A total of 87 Atlases were successfully released in 77 cases. Angiography performed immediately after the embolization revealed 19 (24.7%) modified Raymond grade Ⅰ, 10 (13.0%) grade Ⅱ, and 48 (62.3%) grade Ⅲa cases. Three perioperative complications were observed including thrombotic events in 2 cases and stent migration in 1 case. A follow-up angiogram was available for 47 aneurysms, and showed that modified Raymond grade Ⅰ occlusion was achieved in 38 (80.9%) cases, grade Ⅱ in 2 (4.3%) cases, and grade Ⅲa in 7 (14.9%) cases. At the 6-month follow-up, 38 patients were cured and 7 were stable, whereas 2 patients experienced a recurrence of aneurysm. Stenosis of the parent artery occurred in 3 (6.4%) cases, including 2 at the head and 1 inside the stent.Conclusions:The results of this preliminary study suggest that Neuroform Atlas stent-assisted coiling has a high occlusion rate and low incidence of complications in the endovascular treatment of aneurysms. However, the effectiveness of this procedure for large aneurysms and long-term outcomes require further investigation.

Analysis of clinical efficacy of first-line immunotherapy combined with radiotherapy in patients with brain metastasis of non-small cell lung cancer / 中华放射肿瘤学杂志

Objective:To evaluate clinical efficacy of first-line immune checkpoint inhibitors (ICI) combined with radiotherapy (RT) in patients with newly diagnosed non-small cell lung cancer (NSCLC) with brain metastasis (BM).Methods:Clinical data of patients with BM of NSCLC diagnosed in Henan Cancer Hospital from December 2017 to June 2021 were retrospectively analyzed. Patients were treated with programmed death-1 (PD-1) / programmed death-ligand 1 (PD-L1) inhibitor combined with or without brain RT. The survival rate was calculated by Kaplan-Meier analysis. Univariate analysis was performed by log-rank test and multivariate analysis was performed by Cox model.Results:The median follow-up time was 13 months (range 4-49 months). The median overall survival (OS) time was 24 months, and the 1-, 2- and 3-year OS rates were 75.8%, 44.7%, and 33.6%, respectively. The 1-year intracerebral progression-free survival (iPFS) was 68.8%. The intracerebral objective response rate (icORR) of the RT-ICI group and ICI group was 71.4% and 52.6%, respectively, and the intracerebral disease control rate (icDCR) was 96.4% and 89.4%, respectively ( P=0.122,0.291). Univariate analysis showed that the 1-, 2- and 3-year OS rates of patients with high graded prognostic assessment (GPA) scores were 100%, 85.7% and 35.7%, respectively. The 1-, 2- and 3-year OS rates of patients with low GPA scores were 68.3%, 33.6% and 33.6%, respectively ( P=0.115). The 1-, 2- and 3-year OS rates of patients in the RT-ICI group were 88.7%, 58.7% and 44.0%, respectively, and 63.6%, 20.9% and 20.9% for their counterparts in the ICI group, respectively ( P=0.022). The 1-, 2- and 3-year OS rates of symptomatic patients with BM were 60.9%, 33.8% and 33.8%, respectively, while 84.6%, 53.1% and 39.8% for asymptomatic counterparts, respectively ( P=0.021). Multivariate analysis showed that no symptoms of BM and brain RT were the independent influencing factors of OS rate ( P=0.038, 0.037). Conclusions:First-line ICI combined with brain RT can improve the survival rate of patients with BM of NSCLC. It is recommended that patients with BM should receive RT as soon as possible, especially those with brain symptoms.

IGFBP-3 promotes cachexia-associated lipid loss by suppressing insulin-like growth factor/insulin signaling / 中华医学杂志(英文版)

BACKGROUND@#Progressive lipid loss of adipose tissue is a major feature of cancer-associated cachexia. In addition to systemic immune/inflammatory effects in response to tumor progression, tumor-secreted cachectic ligands also play essential roles in tumor-induced lipid loss. However, the mechanisms of tumor-adipose tissue interaction in lipid homeostasis are not fully understood.@*METHODS@#The yki -gut tumors were induced in fruit flies. Lipid metabolic assays were performed to investigate the lipolysis level of different types of insulin-like growth factor binding protein-3 (IGFBP-3) treated cells. Immunoblotting was used to display phenotypes of tumor cells and adipocytes. Quantitative polymerase chain reaction (qPCR) analysis was carried out to examine the gene expression levels such as Acc1 , Acly , and Fasn et al .@*RESULTS@#In this study, it was revealed that tumor-derived IGFBP-3 was an important ligand directly causing lipid loss in matured adipocytes. IGFBP-3, which is highly expressed in cachectic tumor cells, antagonized insulin/IGF-like signaling (IIS) and impaired the balance between lipolysis and lipogenesis in 3T3-L1 adipocytes. Conditioned medium from cachectic tumor cells, such as Capan-1 and C26 cells, contained excessive IGFBP-3 that potently induced lipolysis in adipocytes. Notably, neutralization of IGFBP-3 by neutralizing antibody in the conditioned medium of cachectic tumor cells significantly alleviated the lipolytic effect and restored lipid storage in adipocytes. Furthermore, cachectic tumor cells were resistant to IGFBP-3 inhibition of IIS, ensuring their escape from IGFBP-3-associated growth suppression. Finally, cachectic tumor-derived ImpL2, the IGFBP-3 homolog, also impaired lipid homeostasis of host cells in an established cancer-cachexia model in Drosophila . Most importantly, IGFBP-3 was highly expressed in cancer tissues in pancreatic and colorectal cancer patients, especially higher in the sera of cachectic cancer patients than non-cachexia cancer patients.@*CONCLUSION@#Our study demonstrates that tumor-derived IGFBP-3 plays a critical role in cachexia-associated lipid loss and could be a biomarker for diagnosis of cachexia in cancer patients.

Prognostic value of metabolic parameters of 18F-FDG PET/CT in advanced non-small cell lung cancer treated with first-line immunotherapy combined with chemotherapy / 中华放射医学与防护杂志

Objective:To investigate the prognostic value of metabolic parameters of 18F-fluorodeoxyglucose ( 18F-FDG) positron emission computed tomography/computed tomography(PET/CT) in advanced non-small cell lung cancer(NSCLC) treated with first-line immune checkpoint inhibitor (ICI) combined with chemotherapy. Methods:A retrospective study was conducted to evaluate patients with advanced NSCLC who underwent baseline PET/CT before treatment at the Affiliated Cancer Hospital of Zhengzhou University from 2019 to 2021. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-offs for metabolic parameters of PET/CT, including total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and maximum standard uptake value (SUV max). Kaplan-Meier method, Log-rank test, and Cox regression model were used to calculate the overall survival (OS) and the progression-free survival(PFS). Results:A total of 44 patients were enrolled. Univariate analysis showed that the factors influencing PFS were TMTV and the number of metastatic sites ( χ2=4.19, 11.28, P<0.05) and the factors influencing OS were TMTV and TLG ( χ2=14.96, 6.05, P<0.05). Multivariate analysis suggested that number of metastatic sites was an independent prognostic marker for PFS ( P=0.011) and TMTV was an independent prognostic marker for OS ( P=0.038). Conclusions:TMTV is a prognostic indicator of OS while the number of metastatic sites is a prognostic indicator of PFS in advanced NSCLC patients who received first-line ICI combined with chemotherapy, but further prospective studies are needed.

Ultra-high dose rate irradiation induced DNA strand break in plasmid DNA / 中华放射医学与防护杂志

Objective:To compare the effects on DNA strand break induced by ultra-high dose rate (FLASH) electron beam and conventional irradiation, and investigate whether FLASH effect was correlated with a reduction of radiation response.Methods:Aqueous pBR322 plasmid was treated with FLASH (125 Gy/s) and conventional irradiation (0.05 Gy/s) under physioxia (4% O 2) and normoxia (21% O 2). Open circle DNA and linear DNA were detected by agarose gel electrophoresis, and the plasmid DNA damage was quantified with an established mathematical model to calculate the relative biological effect (RBE) of DNA damage. In some experiments, Samwirin A (SW) was applied to scavenge free radicals generated by ionizing radiation. Results:Under physioxia, the yields of DNA strand breakage induced by both FLASH and conventional irradiation had a dose-dependent manner. FLASH irradiation could significantly decrease radiation-induced linear DNA compared with conventional irradiation ( t=5.28, 5.79, 7.01, 7.66, P<0.05). However, when the aqueous plasmid was pretreated with SW, there was no difference of DNA strand breakage between FLASH and conventional irradiation ( P>0.05). Both of the yields of open circle DNA and linear DNA had no difference caused by FLASH and conventional radiotherapy at normoxia, but were significantly higher than those under physioxia. In addition, the yields of linear DNA and open circle DNA induced by FLASH irradiation per Gy were (2.78±0.03) and (1.85±0.17) times higher than those of conventional irradiation, respectively. Conclusions:FLASH irradiation attenuated radiation-induced DNA damage since a low production yield of free radical in comparison with conventional irradiation, and hence the FLASH effect was correlated with oxygen content.

Clinical features and laboratory characteristics of 4 cases of aromatic L-amino acid decarboxylase deficiency / 中华神经科杂志

Objective:To investigate the clinical characteristics, laboratory characteristics and genetic diagnosis of aromatic L-amino acid decarboxylase deficiency (AADCD), and to improve the understanding of this disease.Methods:Four children diagnosed with AADCD from the Department of Neurology, Beijing Children′s Hospital Affiliated to Capital Medical University from August 2016 to June 2020 were collected, and their clinical manifestations, laboratory and imaging data, and genetic test results were retrospectively analyzed.Results:All the 4 cases were diagnosed in early infancy, with the first symptom of feeding difficulties. They developed paroxysmal dyspraxia accompanied by eye movement crisis, movement regression, hypotonia, growth retardation, sleep disorders and autonomic nervous symptoms such as ptosis, excessive sweating and nasal congestion at the age of 2-4 months, respectively. The 4 children were siblings from 2 families with healthy parents. The dihydroxyphenylalanine decarboxylase ( DDC) gene mutations in cases 1 and 2 were derived from the maternal missense mutation c.1040G>A(P.RG347gln), and from the paternal deletion of exons 11 and 12, respectively. The DDC gene mutation in case 3 was derived from the maternal mutation c.419G>A(p.G140E) and the paternal mutation c.1375C>T(p.H459Y), respectively. Case 4 did not undergo genetic testing. Blood amino acid and acylcarnitine profiles and urine organic acid analyses were performed in 3 cases, and no specific abnormalities were found. In case 3, the results of 3-O-methyldopa (3-OMD) screening by blood dry filter paper increased significantly. Cerebrospinal fluid neurotransmitter detection results showed that the concentrations of 3-methoxy-4-hydroxyphenyldiol, vanillic acid and 5-hydroxyindoleacetic acid were significantly decreased, while the levels of 5-hydroxytryptophan and 3-OMD were increased in case 3. Blood aromatic L-amino acid decarboxylase (AADC) activity decreased significantly in case 3. Cranial magnetic resonance imaging (MRI) and electroencephalogram (EEG) examinations were performed in cases 1, 3, and 4, among which the cranial MRI in case 1 was normal, while the cranial MRI in cases 3 and 4 suggested that myelination was slightly backward. The EEG was normal in all the 3 cases. Cases 1 and 2 died of pneumonia and respiratory failure at the age of 1 year and 10 months. Case 3 was given clonazepam, benxel hydrochloride tablets and vitamin B6 tablets orally after diagnosis at the age of 4 months, and then treated with selegiline hydrochloride tablets and pramexol hydrochloride tablets. At the follow-up of 1 year and 6 months, the frequency of eye movement crisis and movement disorder was reduced, sleep was improved and autonomic nervous symptoms were alleviated, but there was no improvement in developmental delay. Case 4 was diagnosed with cerebral palsy and epilepsy, but failed various antiepileptic drugs and rehabilitation training, and died at the age of 10 due to heart failure and kidney failure. Conclusions:The clinical manifestations of AADCD are complicated and the misdiagnosis rate is high. Infants with early-onset hypotonia, developmental retardation, eye movement crisis, and movement disorders should be screened with dry filter paper as soon as possible for 3-OMD level, and suspicious cases should be diagnosed by cerebrospinal fluid neurotransmitter detection, plasma AADC activity determination, and gene examination. Early diagnosis of AADCD in children and gene mutation carriers can guide treatment and provide genetic counseling to reduce the incidence of the offspring.

Analysis of preoperative risk factors for prolonged mechanical ventilation after pulmonary thromboendarterectomy / 中国胸心血管外科临床杂志

@#Objective     To identify the preoperative risk factors for prolonged mechanical ventilation (PMV) after pulmonary thromboendarterectomy (PTE). Methods    The clinical data of patients who underwent PTE from December 2016 to August 2021 in our hospital were retrospectively analyzed. The patients were divided into two groups according to the postoperative mechanical ventilation time, including a postoperative mechanical ventilation time≤48 h group (≤48 h group) and a postoperative mechanical ventilation time>48 h (PMV) group (>48 h group). Univariable and logistic regression analysis were used to identify the preoperative risk factors for postoperative PMV. Results    Totally, 90 patients were enrolled in this study. There were 40 patients in the ≤48 h group, including 30 males and 10 females, with a mean age of 45.48±12.72 years, and there were 50 patients in the >48 h group, including 29 males and 21 females, with a mean age of 55.50±10.42 years. The results showed that in the ≤48 h group, the median postoperative ICU stay was 3.0 days, and the median postoperative hospital stay was 15.0 days; in the >48 h group, the median postoperative ICU stay was 7.0 days, and the median postoperative hospital stay was 20.0 days. The postoperative PMV was significantly correlated with tricuspid annular plane systolic excursion (TAPSE) [OR=0.839, 95%CI (0.716, 0.983), P=0.030], age [OR=1.082, 95%CI (1.034, 1.132), P=0.001] and pulmonary vascular resistance (PVR) [OR=1.001, 95%CI (1.000, 1.003), P=0.028]. Conclusion    Age and PVR are the preoperative risk factors for PMV after PTE, and TAPSE is the preoperative protective factor for PMV after PTE.