[Analysis of problems and management of in vitro diagnostic reagent clinical trials in medical laboratory].

Clinical trials are an important method for evaluating the safety and efficacy of in vitro diagnostic reagents, and are a key basis for product registration review and approval. In order to strengthen the management of clinical trials of in vitro diagnostic reagents, the National Medical Products Administration and relevant departments have formulated a series of regulations at the regulatory level, and require applicants and clinical trial institutions to establish a quality management system for clinical trials of in vitro diagnostic reagents. Medical laboratory is the main department and implementer of in vitro diagnostic reagent clinical trials in medical institutions. In recent years, with the rapid development of the in vitro diagnostic industry, the clinical trial projects of in vitro diagnostic reagents conducted by medical laboratory have been increasing day by day. However, there are currently few discussions on the clinical trial of in vitro diagnostic reagents from the perspective of researchers. Therefore, this article summarizes the characteristics of clinical trials of in vitro diagnostic reagents, analyzes the problems and difficulties in conducting clinical trials of in vitro diagnostic reagents in current medical laboratories, and introduces the laboratory's experience in management; to provide reference for medical testing laboratories that have not yet conducted or have already conducted clinical trials of in vitro diagnostic reagents, in order to improve the quality and efficiency of clinical trials.

[A multicenter study on the effects of congenital cytomegalovirus infection on hearing loss].

Objective: To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes. Methods: A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results: Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement (RR=4.58,95%CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group (RR=0.90, 95%CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL (OR=11.58, 95%CI 2.10-63.93, P=0.005) and preterm birth (OR=4.98, 95%CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions: SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.

[A cross-sectional survey on the allocation of nursing human resources in burn centers in China].

Objective: To investigate the allocation of nursing human resources in burn centers in China. Methods: A cross-sectional survey was conducted. Using a self-designed questionnaire, a survey was carried out from January to March 2022 to investigate the January to December 2021 status of 39 burn centers in China that met the inclusion criteria based on six strategic regions and other regions, including the hospital grade and the region, the number of nurses and opening beds in the burn centers and burn intensive care units (BICUs), the age, working seniority in burn specialty, educational background, professional title, personnel employment, and turnover of nurses and training of newly recruited nurses in the burn centers. Results: This survey covered 30 provinces, municipalities, and autonomous regions in China (excluding Hong Kong Special Administrative Region, Macao Special Administrative Region, and Taiwan region of China). A total of 39 questionnaires were collected, all of which were valid. The 39 burn centers were located in 38 tertiary A hospitals and 1 tertiary B hospital, with 26 burn centers in strategic areas. The nurse/bed ratio of burn centers in the Greater Bay Area of Guangdong, Hong Kong, and Macao was the highest, while the nurse/bed ratio of burn centers in border ethnic minority area was the lowest. Except for the Chengdu-Chongqing Economic Circle, BICUs had been set up in burn centers in other regions. Among the 39 burn centers, the percentage of nurses aged 25 to 34 years was 51.21% (738/1 441), the percentage of nurses worked in burn specialty for less than 5 years was 31.16% (449/1 441), the percentage of nurses with bachelor's degree was 69.74% (1 005/1 441), and the percentage of nurses with nursing professional title was 44.14% (636/1 441), which were the highest. There were significant differences in the employment of nurses, the percentage of permanent nurses in burn centers in the collaborative development zone of Beijing-Tianjin-Hebei was 82.48% (113/137), while the percentage of permanent nurses in burn centers in important military strategic area was only 9.42% (34/361); the turnover rate of nurses was 9.03% (143/1 584), among which the turnover rate of nurses was 18.14% (80/441) in burn centers in important military strategic area. The training for newly recruited nurses in 39 burn centers was mainly based on the guidance of senior nurses and the pre-job education+specialist training. Conclusions: The burn nursing human resources in strategic areas in China are seriously insufficient and unevenly distributed, with unstable nurse team and lack of standardized specialist training. In particular, the nursing human resources in BICUs need to be equipped and supplemented urgently.

Drug efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of postmenopausal osteoporosis: a network meta-analysis of randomized controlled trials.

OBJECTIVE: This study aims to compare the efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of women with postmenopausal osteoporosis. MATERIALS AND METHODS: Randomized controlled trials (RCTs) were searched in Medline, Embase, and Cochrane up to April 2022. Statistical analysis was performed using R 4.1.3 software, and quality evaluation was conducted using Review Manager 5.3. RESULTS: 51 RCTs containing 39,095 patients met our selection criteria. The efficacy results indicated that teriparatide was more effective than ibandronic acid in reducing vertebral fractures [relative risk (RR) = 0.536; 95% confidence interval (CI) (0.266, 0.998)]. Denosumab [mean difference (MD) = -4.19; 95% CI (-8.03, -0.355)] and teriparatide [MD = 4.64; 95% CI (1.60, 7.72)] showed better efficacy than ibandronic acid in improving spine bone mineral density (BMD). Denosumab showed better efficacy than teriparatide in improving radius BMD [MD = -4.14; 95% CI (-6.72, -1.54)], hip bone mineral density (BMD) [MD = -2.01; 95% CI (-3.80, -0.162)], and one-third radius BMD [MD = -3.63; 95% CI (-7.04, -0.151)]. Denosumab was associated with the greatest benefit in increasing radius BMD [the surface under the cumulative ranking curve area (SUCRA) = 0.999], hip BMD [surface under the cumulative ranking curve area (SUCRA) = 0.979], femoral neck BMD (SUCRA = 0.971), one-third radius BMD (SUCRA = 0.994) and preventing vertebral fractures (SUCRA = 0.806). Teriparatide was associated with the greatest benefit in preventing non-vertebral fractures (SUCRA = 0.927) and improving spine BMD (SUCRA = 0.899). The safety results indicated that teriparatide was safer than zoledronic acid regarding the risk of adverse events [RR = 0.958; 95% CI (0.919, 0.988)]. Teriparatide was associated with the greatest benefit in preventing adverse events (SUCRA = 0.908) and serious adverse events (SUCRA = 0.813). CONCLUSIONS: Our current results suggested that when considering both safety and efficacy, denosumab or teriparatide might be a better choice for women with postmenopausal osteoporosis.

[Progress in surgical treatment of hepatocellular carcinoma with tumor thrombus in the inferior vena cava].

Hepatocellular carcinoma(HCC) is one of the most common malignancies of the digestive system,which is prone to be associated with microvascular or macrovascular invasion. Among them,HCC with inferior vena cava tumor thrombus(IVCTT) or right atrium tumor thrombus(RATT) is rare and has a poor prognosis. However,surgical treatment of HCC with IVCTT and (or) RATT is rarely reported and summarized. The review described the classification of HCC tumor thrombus with IVCTT and (or) RATT, summarized the progress of surgical approaches and surgical operations,and introduced a case of thrombectomy after pushing from the outer surface of the atrium,rendering the RATT to the inferior vena cava under non-cardiopulmonary bypass. The review also proposed the prospective treatments for HCC with IVCTT or RATT,providing clinical guidance to hepatobiliary surgeons.

Computed Tomography scanning in patients with COVID-19: artificial intelligence analysis of lesions volume and outcome.

OBJECTIVE: The aim of this study was to summarize the computed tomography (CT) chest scanning results of COVID-19 patients, and to assess the value of artificial intelligence (AI) dynamics and quantitative analysis of lesion volume change for the evaluation of the disease outcome. PATIENTS AND METHODS: First chest CT and reexamination imaging data of 84 patients diagnosed with COVID-19 who were treated at Jiangshan Hospital of Guiyang, Guizhou Province from February 4, 2020, to February 22, 2020, were retrospectively analyzed. Distribution, location, and nature of lesions were analyzed according to the characteristics of CT imaging and COVID-19 diagnosis and treatment guidelines. Based on the results of the analysis, patients were divided into the group without abnormal pulmonary imaging, the early group, the rapid progression group, and the dissipation group. AI software was used to dynamically measure the lesion volume in the first examination and in the cases with more than two reexaminations. RESULTS: There were statistically significant differences in the age of patients between the groups (p<0.01). The first chest CT examination of the lung without abnormal imaging findings mainly occurred in young adults. Early and rapid progression was more common in the elderly, with a median age of 56 years. The ratio of the lesion to the total lung volume was 3.7 (1.4, 5.3) ml 0.1%, 15.4 (4.5, 36.8) ml 0.3%, 115.0 (44.5, 183.3) ml 3.33%, 32.6 (8.7, 98.0) ml 1.22% in the non-imaging group, early group, rapid progression group, and dissipation group, respectively. Pairwise comparison between the four groups was statistically significant (p<0.001). AI measured the total volume of pneumonia lesions and the proportion of the total volume of pneumonia lesions to predict the receiver operating characteristic (ROC) curve from early development to rapid progression, with a sensitivity of 92.10%, 96.83%, specificity of 100%, 80.56%, and the area under the curve of 0.789. CONCLUSIONS: Accurate measurement of lesion volume and volume changes by AI technology is helpful in assessing the severity and development trend of the disease. The increase in the lesion volume proportion indicates that the disease has entered a rapid progression period and is aggravated.

Measurement of the

The ^{18}O(α,γ)^{22}Ne reaction is critical for AGB star nucleosynthesis due to its connection to the abundances of several key isotopes, such as ^{21}Ne and ^{22}Ne. However, the ambiguous resonance energy and spin-parity of the dominant 470 keV resonance leads to substantial uncertainty in the ^{18}O(α,γ)^{22}Ne reaction rate for the temperature of interest. We have measured the resonance energies and strengths of the low-energy resonances in ^{18}O(α,γ)^{22}Ne at the Jinping Underground Nuclear Astrophysics experimental facility (JUNA) with improved precision. The key 470 keV resonance energy has been measured to be E_{α}=474.0±1.1 keV, with such high precision achieved for the first time. The spin-parity of this resonance state is determined to be 1^{-}, removing discrepancies in the resonance strengths in earlier studies. The results significantly improve the precision of the ^{18}O(α,γ)^{22}Ne reaction rates by up to about 10 times compared with the previous data at typical AGB temperatures of 0.1-0.3 GK. We demonstrate that such improvement leads to precise ^{21}Ne abundance predictions, with an impact on probing the origin of meteoritic stardust SiC grains from AGB stars.

[Introduction and implications of WHO position paper: vaccines against influenza, May 2022].

On May 13, 2022, World Health Organization(WHO) Position Paper on Influenza Vaccine (2022 edition) was published. This position paper updates information on influenza epidemiology, high risk population, the impact of immunization on disease, influenza vaccines and effectiveness and safety, and propose WHO's position and recommendation that all countries should consider implementing seasonal influenza vaccine immunization programmes to prepare for an influenza pandemic. In addition, it proposes that the influenza surveillance platform can be integrated with the surveillance of other respiratory viruses, such as SARS-CoV-2 and Respiratory Syncytial Virus. This position paper has some implications for the prevention and control of influenza and other respiratory infectious diseases in China: (1) Optimize influenza vaccine policies to facilitate the implementation of immunization services; (2) Influenza prevention and control should from the perspective of Population Medicine focus on the individual and community to integrate with "Promotion, Prevention, Diagnosis, Control, Treatment, Rehabilitation"; (3) Incorporate prevention and control of other respiratory infectious diseases such as influenza, COVID-19, respiratory syncytial virus and adenovirus, and intelligently monitor by integrating multi-channel data to achieve the goal of co-prevention and control of multiple diseases.

[Validation of the Pollard' s classification criteria (2010) for rheumatoid arthritis patients with fibromyalgia].

OBJECTIVE: To evaluate the sensitivity and specificity of Pollard' s classification criteria(2010) for the diagnosis of rheumatoid arthritis (RA) patients withfibromyalgia (FM) in Chinese patients, and to assess the clinical features and psychological status of RA-FM patients in a real-world observational setting. METHODS: Two hundred and two patients with rheumatoid arthritis were enrolled from the outpatients in Rheumatology and Immunology Department in Peking University People' s Hospital. All the patients were evaluated whether incorporating fibromyalgia translation occured using the 1990 American College of Rheumatolgy (ACR)-FM classification criteria. Forty two RA patients were concomitant with FM, while the other one hundred and sixty RA patients without FM were set as the control group. RESULTS: There was no significant difference in general demography between the two groups (P>0.05). In this study, the Pollard' s classification criteria (2010) for RA-FM in Chinese patients had a high sensitivity of 95.2% and relatively low specificity of 52.6%. Compared with those patients without FM, RA patients with FM (RA-FM patients) had higher Disease Activity Scale in 28 joints (DAS-28) score (5.95 vs. 4.38, P=0.011) and much more 28-tender joint counts (TJC) (16.5 vs.4.5, P < 0.001).RA-FM patients had worse Health Assessment Questionnaire (HAQ) score (1.24 vs. 0.66, P < 0.001) and lower SF-36 (28.63 vs. 58.22, P < 0.001). Fatigue was more common in RA-FM patients (88. 1% vs. 50.6%, P < 0.001) and the degree of fatigue was significantly increased in RA-FM patients (fatigue VAS 5.55 vs. 3.55, P < 0.001). RA-FM patients also had higher anxiety (10 vs.4, P < 0.001) and depression scores (12 vs.6, P < 0.001). erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), morning stiffness time and 28-swollen joint counts (SJC) showed no difference between these two groups. CONCLUSION: The Pollard' s classification criteria (2010) for RA-FM are feasible in Chinese rheumatoid arthritis patients. The Pollard' s classification criteria is highly sensitive in clinical application, while the relativelylow specificity indicates that various factors need to be considered in combination. RA patients with FM result in higher disease activity, worse function aland psychological status. RA patients with FM also have poorer quality of life. DAS-28 scores may be overestimated in RA patients with FM. In a RA patient thatdoes not reach remission, the possibility of fibromyalgia should be con-sidered.

The potential roles of RNA N6-methyladenosine in atherosclerosis.

OBJECTIVE: Atherosclerosis, characterized by endothelial injury, multicellular involvement, chronic inflammation, and lipid deposition, can lead to acute cardiovascular events. N6-methyladenosine (m6A) is the most abundant, prevalent RNA modification in mammalian cells. m6A, a reversible modification, can be catalyzed by m6A methyltransferase complexes (writers), reverted by demethylases (erasers), and recognized by m6A-binding proteins (readers). Emerging evidence suggests that m6A modification plays a significant role in regulating many biological and cellular processes in atherosclerosis. In this review, we highlight the biological function of m6A modification and give a brief perspective on its future applications in atherosclerosis. MATERIALS AND METHODS: This is a narrative review. The literature search strategy for indexed Scopus articles was performed randomly using PubMed and MEDLINE as the primary sources. No specific term was used. RESULTS: As the mechanism of the relationship between inflammatory response and atherosclerosis, m6A has become a new focus in the study of clinical treatment strategies for atherosclerosis. METTL14-dependent m6A modification may be a target for atherosclerosis therapy. A variety of m6A regulatory factors promote the progression of atherosclerosis by regulating polarization and inflammation of macrophages. WTAP and METTL14 can affect the phenotypic modulation of VSMCs through m6A modification. CONCLUSIONS: The existence of m6A in cardiovascular transcripts is necessary to maintain cardiac function, and the level of m6A modification is increased in a variety of atherosclerotic vascular cells, indicating that m6A modification is involved in the pathophysiological process of atherosclerosis. m6A modification plays an important character in atherosclerosis.

[Historical changes of a missionary hospital - Shanghai General Hospital (1864-1953)].

The Christian missionaries preached through medicine by combining religious preaching with secularisation and social adaptiveness of medicine in the 19th century. They attempted to avoid the negative influence of culture differences between the West and China. Desjacques Marin, one of the missionaries in China, was entrusted by Benoit Edan, a French consul in Shanghai to establish a hospital in 1864, named the "General Hospital". This hospital was moved to the north bank of Suzhou Creek in 1877 and renamed as the Gongji Hospital. The hospital was designated by the Japanese Army in 1940 as a hospital for sick foreign prisoners in the war. It was taken over as an enemy property by the government of the Republic of China in 1945 and became a public hospital opened formally to Chinese patients. It was renamed as "Shanghai First People's Hospital" in 1953. Review of the historical changes of the missionary hospital is of significance for the study on Chinese medical history and medical communication between China and the West.

[Interpretation of updated international guidelines for diagnosis and treatment of gastroenter-opancreatic neuroendocrine neoplasms].

The incidence of neuroendocrine neoplasms (NEN) is continuously increasing with gastrointestinal tract and pancreas being the most common primary sites. Currently, the guidelines proposed by European Neuroendocrine Tumor Society (ENETS), National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) and North American Neuroendocrine Tumor Society (NANETS) are being widely applied. Among these, ENETS and NANETS guidelines were proposed in 2017 while ESMO and NCCN recently updated their guidelines for gastroenteropancreatic NEN in 2020 and 2021, respectively. This article interprets the diagnosis and treatment of gastroenteropancreatic NEN based on the newly updated ESMO and NCCN guidelines. The diagnosis of gastroenteropancreatic NEN depends on histological assessment including morphological evaluation, grading and immunohistochemistry results. Combination of different imaging methods can help determine tumor staging and risk assessment. Decision-making of treatment and follow-up strategies is based on primary tumor site, tumor classification, tumor grade, tumor type, functional status etc.

[Comparison of clinical characteristics between sporadic gastrinoma and multiple endocrine neoplasia type 1-related gastrinoma].

Objective: To compare clinical characteristics of sporadic gastrinoma and multiple endocrine neoplasia type 1 (MEN1)-related gastrinoma. Methods: A retrospective cohort study was conducted. Patients with clinical manifestations of Zollinger-Ellison syndrome, pathological diagnosis as neuroendocrine neoplasm (NEN) and complete clinical and follow-up data were enrolled. Patients with only high gastric acid secretion but without evidence of NEN, or with other concurrent non-NEN tumors were excluded. According to the above criteria, the clinicopathological data of 52 cases of gastrinoma diagnosed from April 2003 to December 2020 in the First Affiliated Hospital, Sun Yat-sen University, were collected. Patients who met the diagnostic criteria of gastrinoma and met one of the following conditions were diagnosed as MEN1-related gastrinoma: (1) the presence of pathogenic mutations in the MEN1 gene confirmed by genetic testing; (2) NENs involving two or more endocrine glands, namely, pituitary, parathyroid, thymic, pancreatic, and adrenal NENs; (3) NEN and at least one first-degree relatives diagnosed as MEN1. The remaining gastrinomas were defined as sporadic gastrinoma. Student's t test and chi-square test were used for statistical analysis. Clinicopathological characteristics, endoscopic findings, imaging characteristics, treatment, and prognosis of sporadic and MEN1-related gastrinoma were compared. Results: Among 52 patients with gastrinoma, 33 were sporadic gastrinoma and 19 were MEN1-related gastrinoma. The common symptoms of both sporadic and MEN1-related gastrinomas were diarrhea (24/33, 72.7%; 17/19, 89.5%) and abdominal pain (19/33, 57.6%; 9/19, 47.4%). Compared with sporadic gastrinoma, MEN1-related gastrinoma needed longer time for diagnosis [(7.4±4.9) years vs. (3.9±5.2) years, t=-2.355, P=0.022), were more likely multiple tumors [47.4% (9/19) vs. 15.2% (5/33), χ(2)=6.361, P=0.012], had smaller diameter [(1.7±1.0) cm vs. (3.1±1.8) cm, t=2.942, P=0.005), presented the lower tumor grade [G1: 83.3% (15/18) vs. 39.4% (13/33); G2: 11.1% (2/18) vs. 54.5% (18/33); G3: 5.6% (1/18) vs. 6.1% (2/33), Z=-2.766, P=0.006], were less likely to have serum gastrin which was 10 times higher than normal [11.8% (2/17) vs. 56.0% (14/33), χ(2)=8.396, P=0.004], had higher probability of complication with type 2 gastric neuroendocrine tumors (g-NET) [31.6% (6/19) vs. 3.0%(1/33), χ(2)=6.163, P=0.013], and had lower rate of liver metastasis [21.1% (4/19) vs. 51.5% (17/33), χ(2)=4.648, P=0.031). There was no obvious difference between sporadic gastrinomas and MEN1-related gastrinomas in endoscopic findings. Both types presented enlarged and swollen gastric mucosa under the stimulation of high gastric acid, and multiple ulcers in the stomach and duodenum could be seen. Gastrinoma with type 2 g-NET presented multiple polypoid raised lesions in the fundus and body of the stomach. (68)Ga-SSR-PET/CT scan had a 100% detection rate for both types while (18)F-FDG-PET/CT scan had a higher detection rate for sporadic gastrinoma compared with MEN1-related gastrinoma [57.9% (11/19) vs. 20.0% (3/15), χ(2)=4.970, P=0.026]. Among the patients with sporadic gastrinoma, 19 received surgical treatment, 1 underwent endoscopic submucosal dissection, 8 underwent transcatheter arterial embolization (TAE), and 5 underwent surgery combined with TAE. Among patients with MEN1-related gastrinoma, 13 received surgical treatment, and the other 6 received conservative treatment. The median follow-up of all the patients was 21.5 (1-129) months, and the 5-year survival rate was 88.4%. The 5-year survival rate of patients with sporadic and MEN1-related gastrinomas was 89.5% and 80.0% respectively (P=0.949). The 5-year survival rate of patients with and without liver metastasis was 76.2% vs. 100%, respectively (P=0.061). Conclusions: Compared with sporadic gastrinoma, MEN1-related gastrinoma has longer diagnosis delay, smaller tumor diameter, lower tumor grading, lower risk of liver metastasis, and is more likely to complicate with type 2 g-NET, while there is no difference in survival between the two tumor types.

[Establishment and validation of a nomogram to predict overall survival of patients with gastric neuroendocrine neoplasms].

Objective: To establish a novel nomogram to predict overall survival of patients with gastric neuroendocrine neoplasms (g-NEN). Methods: A case control study was conducted. Clinicopathological and follow-up data of patients with g-NEN who were treated in two academic medical centers in Southern China between July 2008 and June 2018 were retrospectively collected, including 174 patients from Sun Yat-sen University Cancer Center and 102 patients from the First Affiliated Hospital of Sun Yat-sen University. Univariate survival analysis using Kaplan-Meier method and multivariate analysis using Cox regression were performed to identify prognostic factors. A nomogram was subsequently established based on prognostic factors. Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the performance of the model according to differentiation, calibration and clinical utility. Results: A total of 276 patients were enrolled in the study, of whom 189 patients were male and 87 were female. The age at diagnosis was below 60 years old in 150 patients and 60 years or older in 126 patients. There were patients diagnosed with gastric neuroendocrine carcinoma (g-NEC) and 101 patients with gastric neuroendocrine tumor (g-NET). The number of patients with primary tumor locating at upper, middle and lower parts of stomach was 131, 98 and 47, respectively. As for TNM stage, 72 patients were categorized as stage I, 26 patients stage II, 93 patients stage III, and 85 patients stage IV. Univariate analysis indicated that age, pathological type, primary site, Ki-67 index, T stage, N stage, and M stage were associated with overall survival of g-NEN patients (all P<0.05). Multivariate regression analysis testified that high Ki-67 index, advanced T stage and advanced M stage were independent prognostic factors (all P<0.05). The C-index of the nomogram was 0.806 (95%CI: 0.769-0.863). The calibration curve of the nomogram showed that the predicted survival rate was consistent with the actual survival rate in g-NEN patients. The ROC curves and DCA showed that the nomogram had better differentiation and clinical utility than the American Joint Committee on Cancer (AJCC) 8th TNM staging system (the area under the ROC curve was 0.862 vs. 0.792). Conclusion: The first nomogram to predict overall survival of patients with g-NEN is established and verified in this study, which provides individual prediction of 3-year overall survival rate and is applicable to both g-NET and g-NEC patients.

Direct Measurement of the Astrophysical

Fluorine is one of the most interesting elements in nuclear astrophysics, where the ^{19}F(p,α)^{16}O reaction is of crucial importance for Galactic ^{19}F abundances and CNO cycle loss in first generation Population III stars. As a day-one campaign at the Jinping Underground Nuclear Astrophysics experimental facility, we report direct measurements of the essential ^{19}F(p,αγ)^{16}O reaction channel. The γ-ray yields were measured over E_{c.m.}=72.4-344 keV, covering the Gamow window; our energy of 72.4 keV is unprecedentedly low, reported here for the first time. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing Underground Laboratory, one of the deepest underground laboratories in the world. The present low-energy S factors deviate significantly from previous theoretical predictions, and the uncertainties are significantly reduced. The thermonuclear ^{19}F(p,αγ)^{16}O reaction rate has been determined directly at the relevant astrophysical energies.

[Rare thalassemia caused by novel nucleotide variants in the globin gene: four case reports and literature review].

Objective: To analyze the DNA sequences and clinical phenotypes of four cases with rare thalassemia to improve its recognition and accurate diagnosis. Methods: The DNA sequence characteristics of four cases with rare thalassemia diagnosed from May 2014 to December 2019 were retrospectively analyzed, and related literature was reviewed. Results: The results of the routine gene test for thalassemia indicated that the common three type of deletion and three point mutations in hemoglobin alpha 1/2 (HBA1/A2) , and 16 point mutations in hemoglobin beta (HBB) gene were unable to be detected in cases 1-3, and case 4 was--SEA. However, the results of HBA1/A2 and HBB whole-genome sequencing revealed that the four cases had a point mutation of HBB:c.347C>A, HBB:c.1A>G, HBB:c.393T>G, and HBA2: c.301-1G>A (IVS II-142 G>A) , respectively. Meanwhile, the father, aunt, and grandfather of case 2 carried the HBB:c.1 A>G heterozygous point mutation. Conclusion: The novel mutations in HBB and HBA2 genes, resulting in a rare thalassemia, were revealed. Among them, the HBB:c.347C>A, HBB:c.1A>G, and HBA2:c.301-1G>A (IVS II-142 G>A) mutations were first reported in Chinese patients with thalassemia. Contrarily, HBB:c.393T>G mutation has not yet been recorded in the databases of human hemoglobin variants and thalassemia. The discovery of these novel nucleotide variants in this study would enrich the DNA mutation gene database of thalassemia.

TGIF2 promotes cervical cancer metastasis by negatively regulating FCMR.

OBJECTIVE: We aimed at studying the correlation between TGIF2 expression and clinicopathological features of cervical cancer (CCa). The relationship between TGIF2 and FCMR and its influence on the proliferation and metastasis of tumor cells were investigated using molecular biology techniques, so as to reveal the pathogenesis of CCa and provide a new target for clinical treatment. PATIENTS AND METHODS: TGIF2 expression in 60 pairs of cervical tumors and paracancerous tissues samples collected from CCa patients of our hospital was studied by quantitative real-time polymerase chain reaction (qPCR) analysis, and the association between TGIF2 expression and the clinical indicators or prognosis of CCa patients were analyzed. CCa cells with TGIF2 knockdown were constructed using transfection technology. Changes in the biological phenotypes (proliferation, migration, invasion) of CCa cells C33-A and HeLa after TGIF2 knockdown were determined by Cell Counting Kit-8 (CCK-8) and transwell assays. In addition, the effects of TGIF2/FCMR axis on CCa metastasis were further explored in nude mice in vivo. RESULTS: Our data revealed a significant increase in TGIF2 mRNA expression in CCa tissue specimens compared to adjacent ones, and the increasing degree was positively correlated with the incidence of lymph node or distant metastasis of CCa patients. The results of CCK-8 and transwell suggested that knocking down TGIF2 effectively attenuated the proliferative ability and invasiveness of CCa cells. Luciferase assay confirmed that TGIF2 can directly bind to the DNA promoter of its target gene FCMR. Simultaneous transfection of sh-TGIF2 and sh-FCMR partially reversed the inhibitory effect of single transfection of TGIF2 knockdown on the malignant progression of CCa. Experiments in nude mice also suggested that TGIF2 could promote CCa tumorigenesis through the modulation of FCMR expression. CONCLUSIONS: In summary, TGIF2 can promote the migration and proliferation ability of cervical cancer cells via down-regulating FCMR. Our study provides a new therapeutic target for the clinical treatment of cervical cancer.

Phytoremediation of heavy metals under an oil crop rotation and treatment of biochar from contaminated biomass for safe use.

The disposal of contaminated plants limits the use of phytoremediation. Therefore, the disposal of contaminated sunflower was investigated after determining the phytoremediation of heavy metals under an oil crop rotation of sunflower (Helianthus annuus L)-sesame (Sesamum indicum L.). In the field experiment, the extraction efficiency of sunflower-sesame rotation was 0.07% for lead (Pb); 1.37% for zinc (Zn); 1.10% for copper (Cu); and 6.12% for cadmium (Cd). Contaminated sunflower stems were pyrolyzed at different temperature. The biochar produced at 300 °C was extracted in a two-step process (acid-extraction from biochar and metals precipitation in alkaline condition). At pH = 1, 65.67% of the Cd and much potassium (K) were extracted. After acid-extraction, adjust the pH of filtrate to 10, metals were precipitated and then separated from the K-enriched solution. Therefore, pyrolysis can process contaminated residues, and the biochar extracts can be reutilized as fertilizer to off-site crop production. Thus, an oil crop-rotation system, in addition to creating economic benefits, can be used by local farmers in contaminated soils.

The modulation of endometriosis by lncRNA MALAT1 via NF-κB/iNOS.

OBJECTIVE: Endometriosis (Ems) is one benign disorder that frequently leads to chronic pelvic pain, dysmenorrhea or even infertility. Featured as the ectopic growth of active endometrial tissues on tissues beyond the muscular layer, Ems has complicated pathogenesis mechanisms that are not fully illustrated. Long non-coding (lnc) RNA MALAT1 participates in various biological activities, including cell growth, proliferation, apoptosis, organogenesis, inflammation, and tumors. However, its expression and function in Ems are not clear yet. PATIENTS AND METHODS: Real-time PCR measured differential expression of MALAT1 in normal and ectopic endometrial tissues. Cultured endometrial cells were transfected with siRNA for MALAT1, whose expression was measured by real-time PCR. MTT assay measured endometrial cell proliferation, whose invasion was measured by transwell assay. Western blot tested the expression and NF-κB/iNOS, and MMP9 proteins. RESULTS: LncRNA MALAT1 showed upregulation in ectopic endometrial tissues (p<0.05 comparing to control group). Transfection of MALAT1 siRNA suppressed its expression in endometrial cells, inhibited cell proliferation or invasion, enhanced caspase 3 activity, decreased NF-κB/iNOS or MMP-9 expression (p<0.05 comparing to control group). CONCLUSIONS: LncRNA MALAT1 can facilitate endometrial cell apoptosis and modulate MMP-9 expression via NF-κB/iNOS pathway, thus, mediating Ems pathogenesis.