Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective:To analyze and summarize the clinical and genetic features of Noonan syndrome (NS) caused by mutations in the leucine zipper-like transcription regulator 1 ( LZTR1) gene. Methods:The retrospective study analyzed a patient who was examined at the Center of Prenatal and Hereditary Disease Diagnosis, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University in January 2021 because of fetal nuchal translucency thickening and a previous history of problematic pregnancies. Subsequently, the patient was diagnosed with Noonan syndrome (NS) through whole exome sequencing. Using keywords such as "Noonan syndrome," "Leucine zipper-like transcription regulator 1", and " LZTR1", clinical and genetic characteristics of NS derived from LZTR1 mutations were summarized by extracting relevant literature from China National Knowledge Infrastructure, Wanfang Database, Yiigle, PubMed and Web of Science, covering from January 2013 to October 2022. Descriptive analysis was applied to the data. Results:(1) Case report: WES and Sanger sequencing showed the existence of the biallelic variants of LZTR1 gene c.842C>T and c.2248G>A in the fetus (Ⅱ-3) and the proband (Ⅱ-2) that inherited from the father and the mother, respectively. Based on the typical special facial appearance and short stature in the proband indicative of NS, the fetus and the proband were diagnosed with autosomal recessive inheritance (AR) NS. The pregnant woman terminated her pregnancy at 22 weeks due to severe edema of the fetus. At the age of three, the proband exhibited typical craniofacial features and short stature characteristics of NS when presented to our hospital. The proband received regular follow-ups in the pediatrics department of other hospitals, where recombinant human growth hormone was used to improve his height. He attended kindergarten at age four and can communicate and play with other children normally. (2) Literature review: 95 cases of NS associated with LZTR1 mutations have been retrieved and included. When including the fetus and the proband of this case, the total reached 97 cases, involving 79 different mutation sites. Forty-three cases (44.3%) were AR, and 54 (55.7%) were autosomal dominant inheritance (AD). Missense mutation was the most prevalent type of mutation, whereas nonsense mutation and frameshift mutation were more common in biallelic variants. Across all cases, the clinical manifestations encompassed multiple systems, primarily characterized by craniofacial dysmorphia, skeletal deformities, heart defects, and short stature. Developmental delay, learning disabilities, and mental retardation of varying degrees may accompany these symptoms. Eighteen cases described antenatal phenotypes, with 16 of them reporting biallelic AR variants. Ultrasound findings of 18 prenatal cases revealed 11 cases of fetal NT thickening, seven cases of cystic hygroma, four cases of fetal pericardium or pleural effusion, two cases of severe fetal edema, and 11 cases of cardiovascular defects. Conclusions:NS induced by LZTR1 mutations is an autosomal dominant or recessive inherited genetic syndrome with a broad spectrum of clinical phenotypes. The severity of the disease varies among children with the same genotype. NS should be considered when prenatal ultrasound indicates nonspecific manifestations, such as fetal NT thickening, cervical lymphatic hydrops, polyhydramnios, fetal edema, and congenital heart defects. Prenatal identification is crucial for evaluating the prognosis of children and assisting families in making clinical decisions.

Aim To investigate the differences in the role of different purinergic receptor subtypes at different sites in postoperative-hyperalgesic priming in mice. Methods A postoperative-hyperalgesic priming model was constructed by injecting PGE

Objective To investigate the effect of chronic restraint stress on the expression of N6-methyladenosine (m6A)and related enzymes in the hippocampus of mice. Methods Twenty C57BL/6J male mice were randomly divided into control group and chronic restraint stress (CRS) group, the model group was given for 3 weeks chronic restraint stress to establish a mouse anxiety model. Open field test and elevated plus maze test were used to detect anxiety-like behavior; Immunohistochemistry and m6A RNA methylation assay were used to detect the expression changes of mouse hippocampal m6A; Western blotting and Real-time PCR were used to analyze hippocampal m6A related enzymes expression. Results 1.The behavioral results showed that, compared with the control group, the CRS group showed significantly reduced time spent in the center of the open field(P<0.01), the CRS group showed significantly reduced exploration time in the open arm of elevated plus maze (P<0.0001); 2. Immunohistochemical results showed that, compared with the control group, the hippocampal m6A content in the CRS group reduced significantly (P < 0.001); The results of the m6A RNA methylation assay showed that, compared with the control group, the CRS group showed significantly reduced amount of hippocampal m6A(P<0.05); 3. Real-time PCR results showed that the expression of hippocampal demethylase anaplastic lymphoma kinase B(AlkB) homolog 5(ALKBH5) (P<0.001) and fat mass and obestity associated protein(FTO) (P< 0.05) in the CRS group significantly up-regulated, the expression of methylase Wilms' tumour 1-associating protein (WTAP) (P<0.05) was significantly down-regulated compared with the control group; The expression of m6A methylation binding protein YTH domaincontaining family protein 3 (YTHDF3) (P < 0.05) and YTH domaincontaining protein 2 (YTHDC2) (P < 0.01) was significantly up-regulated. Western blotting result showed that, compared with the control group, the mouse hippocampal demethylase ALKBH5 (P < 0.05) and FTO (P < 0.05) expression in the CRS group significantly up-regulated, the expression of WTAP (P<0.01) was significantly down-regulated; m6A methylation binding protein YTHDF3 (P<0.01) and YTHDC2 (P<0.05) were significantly up-regulated. Conclusion In the anxiety model induced by chronic restraint stress, the expression of m6A in the hippocampus of mice is down-regulated. The mechanism may be related to the up-regulation of the m6A demethylase ALKBH5 and FTO or the down-regulation of the methylase WTAP.

Objective: Whether metabolic redistribution occurs in patients with white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is unknown. This study aimed 1) to propose a measure of the brain metabolic network for an individual patient and preliminarily apply it to identify impaired metabolic networks in patients with WMHs, and 2) to explore the clinical and imaging features of metabolic redistribution in patients with WMHs. Materials and Methods: This study included 50 patients with WMHs and 70 healthy controls (HCs) who underwent 18F-fluorodeoxyglucose-positron emission tomography/MRI. Various global property parameters according to graph theory and an individual parameter of brain metabolic network called “individual contribution index” were obtained. Parameter values were compared between the WMH and HC groups. The performance of the parameters in discriminating between the two groups was assessed using the area under the receiver operating characteristic curve (AUC). The correlation between the individual contribution index and Fazekas score was assessed, and the interaction between age and individual contribution index was determined. A generalized linear model was fitted with the individual contribution index as the dependent variable and the mean standardized uptake value (SUVmean) of nodes in the whole-brain network or seven classic functional networks as independent variables to determine their association. Results: The means ± standard deviations of the individual contribution index were (0.697 ± 10.9) x 10-3 and (0.0967 ± 0.0545) x 10-3 in the WMH and HC groups, respectively (p < 0.001). The AUC of the individual contribution index was 0.864 (95% confidence interval, 0.785–0.943). A positive correlation was identified between the individual contribution index and the Fazekas scores in patients with WMHs (r = 0.57, p < 0.001). Age and individual contribution index demonstrated a significant interaction effect on the Fazekas score. A significant direct association was observed between the individual contribution index and the SUVmean of the limbic network (p < 0.001). Conclusion The individual contribution index may demonstrate the redistribution of the brain metabolic network in patients with WMHs.

OBJECTIVE: To observe the clinical therapeutic effect of filiform-fire needling of "Biaoben acupoint combination" on the sequelae of patients with coronavirus disease 2019 (COVID-19) during the recovery period. METHODS: A total of 33 patients with COVID-19 during the recovery period were treated with filiform-fire needling at the acupoints of Mingmen (GV 4), Shenzhu (GV 12), Gaohuang (BL 43), Zusanli (ST 36) and Shangjuxu (ST 37), etc., once every other day, 3 times a week, and 3 times was one course of treatment and totally 2 courses of treatment were required. The TCM symptom, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) scores, pulmonary function indexes (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], peak expiratory flow [PEF]) and chest CT imaging change were observed before and after treatment, and the therapeutic effect was evaluated. RESULTS: After treatment, the scores of TCM symptom, HAMA and HAMD were decreased compared with those before treatment (P<0.05), and the levels of FVC, FEV1 and PEF were increased compared with those before treatment (P<0.05), and the recovery rate of 22 patients with pulmonary ventilation dysfunction was 86.4% (19/22). After treatment, the lung shadow area was smaller than that before treatment (P<0.05). The effective rate of 25 patients with lung CT abnormalities was 84.0% (21/25). After treatment, 23 cases were cured, 5 cases were markedly effective, 4 cases were effective, 1 case was ineffective, the cured and markedly effective rate was 84.8%. CONCLUSION The filiform-fire needling of "Biaoben acupoint combination" could significantly reduce the sequelae of cough, fatigue, chest tightness, etc. and mental symptoms such as anxiety and depression in patients with COVID-19 during the recovery period, and promote inflammatory exudation absorption of pulmonary lesion and improve lung ventilation function.
Acupuncture Points ; Acupuncture Therapy ; COVID-19/therapy* ; Humans ; Lung ; Vascular Surgical Procedures

China/epidemiology* ; Diabetes Complications/epidemiology* ; Diabetes Mellitus/epidemiology* ; Humans

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

Coronavirus disease 2019 (COVID-19) has become a serious global public threat. With the progress of research, we have more comprehensive understanding of the COVID-19. Current advances on the etiology, transmission, clinical features, diagnosis and treatment of COVID-19, as well as the experience in the management of COVID-19 will be introduced in this article.